Ignite Creation Date:
2025-12-25 @ 4:33 AM
Ignite Modification Date:
2026-02-20 @ 3:15 PM
Study NCT ID:
NCT05492318
Status:
COMPLETED
Last Update Posted:
2025-01-06
First Post:
2022-06-09
Is Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Perpetrator DDI Potential of Givinostat as Inhibitor and Inducer of CYP3A and P-gp Activity
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'interventionBrowseModule': {'meshes': [{'id': 'C575255', 'term': 'givinostat'}, {'id': 'C502418', 'term': 'givinostat hydrochloride'}, {'id': 'D008874', 'term': 'Midazolam'}, {'id': 'D000069604', 'term': 'Dabigatran'}, {'id': 'D006244', 'term': 'Hardness'}], 'ancestors': [{'id': 'D001569', 'term': 'Benzodiazepines'}, {'id': 'D001552', 'term': 'Benzazepines'}, {'id': 'D006574', 'term': 'Heterocyclic Compounds, 2-Ring'}, {'id': 'D000072471', 'term': 'Heterocyclic Compounds, Fused-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}, {'id': 'D011725', 'term': 'Pyridines'}, {'id': 'D006573', 'term': 'Heterocyclic Compounds, 1-Ring'}, {'id': 'D001562', 'term': 'Benzimidazoles'}, {'id': 'D055595', 'term': 'Mechanical Phenomena'}, {'id': 'D055585', 'term': 'Physical Phenomena'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'p.bettica@italfarmacogroup.com', 'phone': '+39 02 64431 (centralino)', 'title': 'Dr. Paolo Bettica, MD', 'organization': 'Italfarmaco SpA'}, 'certainAgreement': {'piSponsorEmployee': False, 'restrictiveAgreement': False}}, 'adverseEventsModule': {'timeFrame': 'Throughout the study and 10-14 days after the End of Study (safety follow-up visit), i.e. up to day 30-34, all TEAEs, considered related or not related to IMPs, were collected.', 'description': 'End-of-study was defined as the last study procedure on Day 11 or at early discontinuation of subjects administered at least one dose of investigational product.\n\nEarly termination procedures were performed as soon as possible after subject withdrawal, within 10-14 days after last participation of the subject in the study, whenever possible', 'eventGroups': [{'id': 'EG000', 'title': 'Midazolam', 'description': 'Midazolam 1mg/ml IV, single dose, was administered on Days 1, 6 and 17, 1 hour after the planned morning time of givinostat administration. Midazolam 2.5 mg single oromucosal solution was administered on Days 2, 7 and 18, 1 hour after the planned morning time of givinostat administration.', 'otherNumAtRisk': 26, 'deathsNumAtRisk': 26, 'otherNumAffected': 26, 'seriousNumAtRisk': 26, 'deathsNumAffected': 0, 'seriousNumAffected': 0}, {'id': 'EG001', 'title': 'Dabigatran', 'description': 'Dabigatran etexilate 75 mg oral hard capsules Dose: 75 mg; Dosage form: hard capsules On Days 1, 6 and 17, dabigatran etexilate 75 mg was administered (with midazolam 1mg IV) 1 hour after the planned morning time of givinostat administration.', 'otherNumAtRisk': 26, 'deathsNumAtRisk': 26, 'otherNumAffected': 26, 'seriousNumAtRisk': 26, 'deathsNumAffected': 0, 'seriousNumAffected': 0}, {'id': 'EG002', 'title': 'Givinostat', 'description': '10 mg/mL oral suspension. Givinostat 10 mg/ml oral suspension was administered once, in the morning, in Days 1, 2, 6, 7, 17 and 18), and twice a day (50 mg as oral suspension), in the morning and in the evening, from the Day 4 to Day 18. On Day 19, only the morning dose was administered.', 'otherNumAtRisk': 26, 'deathsNumAtRisk': 26, 'otherNumAffected': 26, 'seriousNumAtRisk': 26, 'deathsNumAffected': 0, 'seriousNumAffected': 0}], 'otherEvents': [{'term': 'Thrombocytopenia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 20, 'numAffected': 19}, {'groupId': 'EG001', 'numAtRisk': 26, 'numEvents': 20, 'numAffected': 19}, {'groupId': 'EG002', 'numAtRisk': 26, 'numEvents': 20, 'numAffected': 19}], 'organSystem': 'Blood and lymphatic system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 24.1'}, {'term': 'Dry eye', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 26, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 26, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Eye disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 24.1'}, {'term': 'Eye pruritus', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 26, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG002', 'numAtRisk': 26, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'Eye disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 24.1'}, {'term': 'Ocular hyperaemia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 26, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 26, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Eye disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 24.1'}, {'term': 'Abdominal discomfort', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 26, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG002', 'numAtRisk': 26, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 24.1'}, {'term': 'Abdominal distension', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 26, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG002', 'numAtRisk': 26, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 24.1'}, {'term': 'Abdominal pain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 26, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 26, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 24.1'}, {'term': 'Diarrhoea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 26, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 26, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 24.1'}, {'term': 'Dyspepsia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 8, 'numAffected': 7}, {'groupId': 'EG001', 'numAtRisk': 26, 'numEvents': 8, 'numAffected': 7}, {'groupId': 'EG002', 'numAtRisk': 26, 'numEvents': 8, 'numAffected': 7}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 24.1'}, {'term': 'Epigastric discomfort', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 26, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG002', 'numAtRisk': 26, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 24.1'}, {'term': 'Faeces soft', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 7, 'numAffected': 5}, {'groupId': 'EG001', 'numAtRisk': 26, 'numEvents': 7, 'numAffected': 5}, {'groupId': 'EG002', 'numAtRisk': 26, 'numEvents': 6, 'numAffected': 4}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 24.1'}, {'term': 'Nausea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 5, 'numAffected': 5}, {'groupId': 'EG001', 'numAtRisk': 26, 'numEvents': 5, 'numAffected': 5}, {'groupId': 'EG002', 'numAtRisk': 26, 'numEvents': 5, 'numAffected': 5}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 24.1'}, {'term': 'Oesophageal discomfort', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 26, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 26, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 24.1'}, {'term': 'Vessel puncture site haemorrhage', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 26, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 26, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 24.1'}, {'term': 'Nasopharyngitis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 26, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 26, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 24.1'}, {'term': 'Blood creatine phosphokinase increased', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 3, 'numAffected': 3}, {'groupId': 'EG001', 'numAtRisk': 26, 'numEvents': 3, 'numAffected': 3}, {'groupId': 'EG002', 'numAtRisk': 26, 'numEvents': 3, 'numAffected': 3}], 'organSystem': 'Investigations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 24.1'}, {'term': 'Blood creatinine increased', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 26, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG002', 'numAtRisk': 26, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'Investigations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 24.1'}, {'term': 'Blood thyroid stimulating hormone increased', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 26, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG002', 'numAtRisk': 26, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'Investigations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 24.1'}, {'term': 'Transaminases increased', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 26, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 26, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Investigations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 24.1'}, {'term': 'Polydipsia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 26, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 26, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Metabolism and nutrition disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 24.1'}, {'term': 'Dizziness', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 26, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG002', 'numAtRisk': 26, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 24.1'}, {'term': 'Dysgeusia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 3, 'numAffected': 3}, {'groupId': 'EG001', 'numAtRisk': 26, 'numEvents': 3, 'numAffected': 3}, {'groupId': 'EG002', 'numAtRisk': 26, 'numEvents': 3, 'numAffected': 3}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 24.1'}, {'term': 'Headache', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 2, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 26, 'numEvents': 2, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 26, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 24.1'}, {'term': 'Migraine', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 26, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 26, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 24.1'}, {'term': 'Presyncope', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 26, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 26, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 24.1'}, {'term': 'Somnolence', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 35, 'numAffected': 17}, {'groupId': 'EG001', 'numAtRisk': 26, 'numEvents': 35, 'numAffected': 17}, {'groupId': 'EG002', 'numAtRisk': 26, 'numEvents': 25, 'numAffected': 17}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 24.1'}, {'term': 'Anxiety', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 26, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 26, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Psychiatric disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 24.1'}, {'term': 'Dysmenorrhoea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 26, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 26, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Reproductive system and breast disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 24.1'}, {'term': 'Bradypnoea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 2, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 26, 'numEvents': 2, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 26, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 24.1'}, {'term': 'Dysphonia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 26, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 26, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 24.1'}, {'term': 'Epistaxis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 26, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 26, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 24.1'}, {'term': 'Oropharyngeal discomfort', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 26, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 26, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 24.1'}, {'term': 'Rhinitis allergic', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 26, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 26, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 24.1'}, {'term': 'Alopecia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 26, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG002', 'numAtRisk': 26, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'Skin and subcutaneous tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 24.1'}, {'term': 'Dry skin', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 10, 'numAffected': 10}, {'groupId': 'EG001', 'numAtRisk': 26, 'numEvents': 10, 'numAffected': 10}, {'groupId': 'EG002', 'numAtRisk': 26, 'numEvents': 9, 'numAffected': 9}], 'organSystem': 'Skin and subcutaneous tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 24.1'}, {'term': 'Erythema', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 26, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 26, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Skin and subcutaneous tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 24.1'}], 'frequencyThreshold': '4'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Cmax for Midazolam, 1-hydroxymidazolam, Following Single Doses of the Parent Drug', 'denoms': [{'units': 'Participants', 'counts': [{'value': '26', 'groupId': 'OG000'}, {'value': '26', 'groupId': 'OG001'}, {'value': '26', 'groupId': 'OG002'}, {'value': '26', 'groupId': 'OG003'}, {'value': '26', 'groupId': 'OG004'}, {'value': '26', 'groupId': 'OG005'}]}], 'groups': [{'id': 'OG000', 'title': 'Midazolam IV Alone (Day 1)', 'description': 'A single dose of midazolam 1 mg i.v. was administered on Day 1, 1 hour after givinostat administration.'}, {'id': 'OG001', 'title': 'Midazolam IV Co-administered With Givinostat (Day 6)', 'description': 'Midazolam IV 1 mg/ml, single dose, was co-administered with givinostat (at Day 6) to study this latter potential inhibitory effect on midazolam.\n\nGivinostat 10 mg/mL oral suspension was administered once, in the morning, in Day 6.'}, {'id': 'OG002', 'title': 'Midazolam IV Co-administered With Givinostat (Day 17)', 'description': 'Midazolam IV 1 mg/ml, single dose, was co-administered with givinostat (at Day 17) to study this latter potential inducing effect on midazolam.\n\nGivinostat 10 mg/mL oral suspension was administered once, in the morning, in Day 17.\n\nGivinostat 10 mg/mL: 10 mg/mL oral suspension. Givinostat 10 mg/ml oral suspension was administered once, in the morning, in Day 17).'}, {'id': 'OG003', 'title': 'Oral Midazolam Alone (Day 2)', 'description': 'A single oral dose of midazolam 2.5 mg oral solution was administered alone.'}, {'id': 'OG004', 'title': 'Oral Midazolam Co-Administered With Givinostat (Day 7)', 'description': 'A single oral dose of midazolam 2.5 mg oral solution was administered, 1 hour after the planned morning time of givinostat administration. The potential Inhibitory Effect of midazolam was assessed'}, {'id': 'OG005', 'title': 'Oral Midazolam Co-Administered With Givinostat (Day 18)', 'description': 'A single oral dose of midazolam 2.5 mg oral solution was administered on day 18, 1 hour after the planned morning time of givinostat administration. The potential inducing effect of midazolam was assessed.'}], 'classes': [{'title': 'midazolam', 'categories': [{'measurements': [{'value': '50482.44', 'groupId': 'OG000', 'lowerLimit': '42802.65', 'upperLimit': '59540.16'}, {'value': '53345.17', 'groupId': 'OG001', 'lowerLimit': '46868.39', 'upperLimit': '60716.97'}, {'value': '46510.23', 'groupId': 'OG002', 'lowerLimit': '38309.42', 'upperLimit': '56466.57'}, {'value': '12695.07', 'groupId': 'OG003', 'lowerLimit': '11193.89', 'upperLimit': '14397.57'}, {'value': '15744.30', 'groupId': 'OG004', 'lowerLimit': '13936.13', 'upperLimit': '17787.09'}, {'value': '17678.67', 'groupId': 'OG005', 'lowerLimit': '15782.69', 'upperLimit': '19802.43'}]}]}, {'title': '1-hydroxymidazolam', 'categories': [{'measurements': [{'value': '1426.41', 'groupId': 'OG000', 'lowerLimit': '1269.56', 'upperLimit': '1602.64'}, {'value': '1306.05', 'groupId': 'OG001', 'lowerLimit': '1146.91', 'upperLimit': '1487.26'}, {'value': '1335.02', 'groupId': 'OG002', 'lowerLimit': '1115.15', 'upperLimit': '1598.25'}, {'value': '4451.49', 'groupId': 'OG003', 'lowerLimit': '3756.90', 'upperLimit': '5274.51'}, {'value': '5229.06', 'groupId': 'OG004', 'lowerLimit': '4445.58', 'upperLimit': '6150.63'}, {'value': '6303.67', 'groupId': 'OG005', 'lowerLimit': '5046.18', 'upperLimit': '7874.53'}]}]}], 'analyses': [{'groupIds': ['OG000', 'OG001'], 'paramType': 'ratio of the geometric least square mean', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '90', 'paramValue': '105.67', 'ciLowerLimit': '91.72', 'ciUpperLimit': '121.74', 'groupDescription': 'Midazolam: Potential Inhibitory Effect of Givinostat on the Pharmacokinetics of Midazolam IV.\n\nCmax', 'nonInferiorityType': 'OTHER', 'nonInferiorityComment': 'please note that GMR corresponds to the ratio of the Geometric LSmeans of Midazolam IV Co-Administered with Givinostat (Day 6) and the Geometric LSmeans of Midazolam of IV Alone (Day 1)'}, {'groupIds': ['OG000', 'OG001'], 'paramType': 'ratio of the geometric least square mean', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '90', 'paramValue': '91.56', 'ciLowerLimit': '86.16', 'ciUpperLimit': '97.31', 'groupDescription': '1-Hydroxymidazolam: Potential Inhibitory Effect of Givinostat on the Pharmacokinetics of Midazolam IV - Cmax', 'nonInferiorityType': 'OTHER', 'nonInferiorityComment': 'please note that GMR corresponds to the ratio of the Geometric LSmeans of Midazolam IV Co-Administered with Givinostat (Day 6) and the Geometric LSmeans of Midazolam of IV Alone (Day 1)'}, {'groupIds': ['OG000', 'OG002'], 'paramType': 'ratio of the Geometric LSmeans', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '90', 'paramValue': '92.13', 'ciLowerLimit': '75.97', 'ciUpperLimit': '111.73', 'groupDescription': 'Midazolam: Potential Inducing Effect of Givinostat on the Pharmacokinetics of Midazolam IV - Cmax', 'nonInferiorityType': 'OTHER', 'nonInferiorityComment': 'please note that GMR corresponds to the ratio of the Geometric LSmeans of Midazolam IV Co-Administered with Givinostat (Day 17) and the Geometric LSmeans of Midazolam of IV Alone (Day 1)'}, {'groupIds': ['OG000', 'OG002'], 'paramType': 'ratio of the Geometric LSmeans', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '90', 'paramValue': '93.59', 'ciLowerLimit': '83.72', 'ciUpperLimit': '104.63', 'groupDescription': '1-Hydroxymidazolam: Potential Inducing Effect of Givinostat on the Pharmacokinetics of Midazolam IV - Cmax', 'nonInferiorityType': 'OTHER', 'nonInferiorityComment': 'please note that GMR corresponds to the ratio of the Geometric LSmeans of Midazolam IV Co-Administered with Givinostat (Day 17) and the Geometric LSmeans of Midazolam of IV Alone (Day 1)'}, {'groupIds': ['OG003', 'OG004'], 'paramType': 'ratio of the Geometric LSmeans', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '90', 'paramValue': '124.02', 'ciLowerLimit': '114.38', 'ciUpperLimit': '134.47', 'groupDescription': 'Midazolam: Potential Inhibitory Effect of Givinostat on the Pharmacokinetics of Oral Midazolam - Cmax', 'nonInferiorityType': 'OTHER', 'nonInferiorityComment': 'GMR corresponds to the ratio of the Geometric LSmeans of Oral Midazolam Co-Administered with Givinostat (Day 7) and the Geometric LSmeans of Oral Midazolam Alone (Day 2)'}, {'groupIds': ['OG003', 'OG004'], 'paramType': 'ratio of the Geometric LSmeans', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '90', 'paramValue': '117.47', 'ciLowerLimit': '104.78', 'ciUpperLimit': '131.69', 'groupDescription': '1-Hydroxymidazolam: Potential Inhibitory Effect of Givinostat on the Pharmacokinetics of Oral Midazolam - Max', 'nonInferiorityType': 'OTHER', 'nonInferiorityComment': 'GMR corresponds to the ratio of the Geometric LSmeans of Oral Midazolam Co-Administered with Givinostat (Day 7) and the Geometric LSmeans of Oral Midazolam Alone (Day 2)'}, {'groupIds': ['OG003', 'OG005'], 'paramType': 'ratio of geometric LS means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '90', 'paramValue': '139.28', 'ciLowerLimit': '128.71', 'ciUpperLimit': '150.67', 'groupDescription': 'Midazolam: Potential Inducing Effect of Givinostat on the Pharmacokinetics of Oral Midazolam - Cmax', 'nonInferiorityType': 'OTHER', 'nonInferiorityComment': 'GMR corresponds to the ratio of the Geometric LSmeans of Oral Midazolam Co-Administered with Givinostat (Day 18) and the Geometric LSmeans of Oral Midazolam Alone (Day 2)'}, {'groupIds': ['OG003', 'OG005'], 'paramType': 'ratio of geometric LS means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '90', 'paramValue': '141.61', 'ciLowerLimit': '122.36', 'ciUpperLimit': '163.88', 'groupDescription': '1-Hydroxymidazolam: Potential Inducing Effect of Givinostat on the Pharmacokinetics of Oral Midazolam - Cmax', 'nonInferiorityType': 'OTHER', 'nonInferiorityComment': 'GMR corresponds to the ratio of the Geometric LSmeans of Oral Midazolam Co-Administered with Givinostat (Day 18) and the Geometric LSmeans of Oral Midazolam Alone (Day 2)'}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': 'In the turn of 24 hours after IV midazolam, single dose, administered at day 1,6,17 or after oral midazolam, single dose, administered at days 2, 7 and 18.', 'description': 'Maximum observed plasma concentration (Cmax) of midazolam and 1-hydroxymidazolam following Administration of Midazolam IV Alone (Day 1) and Co-Administration of Midazolam IV and Givinostat (Day 6 - Potential Inhibitory Effect, and Day 17 - Potential Inducing Effect) and following Administration of Oral Midazolam Alone (Day 2) and Co-Administration of Oral Midazolam and Givinostat (Day 7 - Potential Inhibitory Effect, and Day 18 - Potential Inducing Effect).\n\n13 blood samples were collected at pre-dose and at 2 minutes, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 9, 12 and 24 hours after the administration of IV midazolam, on Days 1, 6 and 17, to determine midazolam and 1-hydroxymidazolam plasma concentrations. 11 blood samples were collected at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 and 24 hours after the administration of oral midazolam, on Days 2, 7 and 18, to determine midazolam and 1-hydroxymidazolam plasma concentrations.', 'unitOfMeasure': 'pg/mL', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED', 'populationDescription': 'PK population: Part 1 Pharmacokinetic Analysis Population includes all subjects enrolled in Part 1 of the study, who provided evaluable pharmacokinetic data for at least one IMP, without deviations affecting pharmacokinetic interpretation.'}, {'type': 'PRIMARY', 'title': 'Cmax for Dabigatran (Total and Free), Following Single Doses of the Parent Drug', 'denoms': [{'units': 'Participants', 'counts': [{'value': '26', 'groupId': 'OG000'}, {'value': '26', 'groupId': 'OG001'}, {'value': '26', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': 'Dabigatran Etexilate Alone (Day 1)', 'description': 'Dabigatran etexilate 75 mg, 1 hard capsule, was administered alone.'}, {'id': 'OG001', 'title': 'Dabigatran Etexilate Co-Administered With Givinostat (Day 6)', 'description': 'Dabigatran etexilate 75 mg, 1 hard capsule, was administered 1 hour after the planned morning time of givinostat.'}, {'id': 'OG002', 'title': 'Dabigatran Etexilate Co-Administered With Givinostat (Day 17)', 'description': 'Dabigatran etexilate 75 mg, 1 hard capsule, was administered 1 hour after the planned morning time of givinostat.'}], 'classes': [{'title': 'total dabigatran', 'categories': [{'measurements': [{'value': '69.44', 'groupId': 'OG000', 'lowerLimit': '51.90', 'upperLimit': '92.92'}, {'value': '51.17', 'groupId': 'OG001', 'lowerLimit': '39.62', 'upperLimit': '66.08'}, {'value': '45.35', 'groupId': 'OG002', 'lowerLimit': '34.87', 'upperLimit': '58.99'}]}]}, {'title': 'free dabigatran', 'categories': [{'measurements': [{'value': '60.19', 'groupId': 'OG000', 'lowerLimit': '44.64', 'upperLimit': '81.14'}, {'value': '44.03', 'groupId': 'OG001', 'lowerLimit': '34.49', 'upperLimit': '56.21'}, {'value': '37.41', 'groupId': 'OG002', 'lowerLimit': '29.01', 'upperLimit': '48.23'}]}]}], 'analyses': [{'groupIds': ['OG000', 'OG001'], 'paramType': 'ratio of the Geometric LSmeans', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '90', 'paramValue': '73.68', 'ciLowerLimit': '60.77', 'ciUpperLimit': '89.33', 'groupDescription': 'Total Dabigatran: Potential Inhibitory Effect of Givinostat on the Pharmacokinetics of Dabigatran Etexilate - Cmax', 'nonInferiorityType': 'OTHER', 'nonInferiorityComment': 'GMR corresponds to the ratio of the Geometric LSmeans of Dabigatran Etexilate Co-Administered with Givinostat (Day 6) and the Geometric LSmeans of Dabigatran Etexilate Alone (Day 1)'}, {'groupIds': ['OG000', 'OG001'], 'paramType': 'ratio of the Geometric LSmeans', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '90', 'paramValue': '70.38', 'ciLowerLimit': '57.94', 'ciUpperLimit': '85.50', 'groupDescription': 'Free Dabigatran: Potential Inhibitory Effect of Givinostat on the Pharmacokinetics of Dabigatran Etexilate - Cmax', 'nonInferiorityType': 'OTHER', 'nonInferiorityComment': 'GMR corresponds to the ratio of the Geometric LSmeans of Dabigatran Etexilate Co-Administered with Givinostat (Day 6) and the Geometric LSmeans of Dabigatran Etexilate Alone (Day 1)'}, {'groupIds': ['OG000', 'OG002'], 'paramType': 'ratio of the Geometric LSmeans', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '90', 'paramValue': '65.31', 'ciLowerLimit': '53.33', 'ciUpperLimit': '79.98', 'groupDescription': 'Total Dabigatran: Potential Inducing Effect of Givinostat on the Pharmacokinetics of Dabigatran Etexilate - Cmax', 'nonInferiorityType': 'OTHER', 'nonInferiorityComment': 'GMR corresponds to the ratio of the Geometric LSmeans of Dabigatran Etexilate Co-Administered with Givinostat (Day 17) and the Geometric LSmeans of Dabigatran Etexilate Alone (Day 1)'}, {'groupIds': ['OG000', 'OG002'], 'paramType': 'ratio of the Geometric LSmeans', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '90', 'paramValue': '62.18', 'ciLowerLimit': '50.86', 'ciUpperLimit': '75.95', 'groupDescription': 'Free Dabigatran: Potential Induction Effect of Givinostat on the Pharmacokinetics of Dabigatran Etexilate. Cmax', 'nonInferiorityType': 'OTHER', 'nonInferiorityComment': 'GMR corresponds to the ratio of the Geometric LSmeans of Dabigatran Etexilate Co-Administered with Givinostat (Day 17) and the Geometric Lsmeans of Dabigatran Etexilate Alone (Day 1)'}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': 'In the turn of 72 hours after administration of dabigatran on day 1,6,17', 'description': 'Maximum observed plasma concentration (Cmax) of total dabigatran and free dabigatran following Administration of Dabigatran Etexilate Alone (Day 1) and Co-Administration of Dabigatran Etexilate and Givinostat (Day 6 - Potential Inhibitory Effect, and Day 17 - Potential Inducing Effect).\n\nFifteen (15) blood samples were collected in K2-EDTA collection tubes at pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours after the administration of dabigatran etexilate, on Days 1, 6 and 17, for the determination of total and free dabigatran plasma concentrations.', 'unitOfMeasure': 'ng/mL', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED', 'populationDescription': 'PK population: Part 1 Pharmacokinetic Analysis Population includes all subjects enrolled in Part 1 of the study, who provided evaluable pharmacokinetic data for at least one IMP, without deviations affecting pharmacokinetic interpretation.'}, {'type': 'PRIMARY', 'title': 'Tmax for Midazolam, 1-hydroxymidazolam, Following Single Doses of the Parent Drug', 'denoms': [{'units': 'Participants', 'counts': [{'value': '26', 'groupId': 'OG000'}, {'value': '26', 'groupId': 'OG001'}, {'value': '26', 'groupId': 'OG002'}, {'value': '26', 'groupId': 'OG003'}, {'value': '26', 'groupId': 'OG004'}, {'value': '26', 'groupId': 'OG005'}]}], 'groups': [{'id': 'OG000', 'title': 'Midazolam IV Alone (Day 1)', 'description': 'A single dose of midazolam 1 mg i.v. was administered on Day 1, 1 hour after givinostat administration.\n\nMidazolam (and dabigatran etexilate) was administered with the subjects in a semi-recumbent position. Subjects remained semirecumbent until at least 3 hours post-dose.'}, {'id': 'OG001', 'title': 'Midazolam IV Co-administered With Givinostat (Day 6)', 'description': 'Midazolam IV 1 mg/ml, single dose, was co-administered with givinostat (at Day 6) to study this latter potential inhibitory effect on midazolam.\n\nGivinostat 10 mg/mL oral suspension was administered once, in the morning, in Day 6.'}, {'id': 'OG002', 'title': 'Midazolam IV Co-administered With Givinostat (Day 17)', 'description': 'Midazolam IV 1 mg/ml, single dose, was co-administered with givinostat (at Day 17) to study this latter potential inducing effect on midazolam.\n\nGivinostat 10 mg/mL oral suspension was administered once, in the morning, in Day 17.'}, {'id': 'OG003', 'title': 'Oral Midazolam Alone (Day 2)', 'description': 'A single oral dose of midazolam 2.5 mg oral solution was administered alone.'}, {'id': 'OG004', 'title': 'Oral Midazolam Co-Administered With Givinostat (Day 7)', 'description': 'A single oral dose of midazolam 2.5 mg oral solution was administered.'}, {'id': 'OG005', 'title': 'Oral Midazolam Co-Administered With Givinostat (Day 18)', 'description': 'A single oral dose of midazolam 2.5 mg oral solution was administered.'}], 'classes': [{'title': 'midazolam', 'categories': [{'measurements': [{'value': '0.03', 'groupId': 'OG000', 'lowerLimit': '0.03', 'upperLimit': '0.03'}, {'value': '0.03', 'groupId': 'OG001', 'lowerLimit': '0.03', 'upperLimit': '0.03'}, {'value': '0.03', 'groupId': 'OG002', 'lowerLimit': '0.03', 'upperLimit': '0.25'}, {'value': '0.55', 'groupId': 'OG003', 'lowerLimit': '0.50', 'upperLimit': '1.50'}, {'value': '0.50', 'groupId': 'OG004', 'lowerLimit': '0.50', 'upperLimit': '1.50'}, {'value': '0.50', 'groupId': 'OG005', 'lowerLimit': '0.50', 'upperLimit': '1.02'}]}]}, {'title': '1-hydroxymidazolam', 'categories': [{'measurements': [{'value': '0.50', 'groupId': 'OG000', 'lowerLimit': '0.25', 'upperLimit': '1.00'}, {'value': '0.50', 'groupId': 'OG001', 'lowerLimit': '0.25', 'upperLimit': '2.00'}, {'value': '0.51', 'groupId': 'OG002', 'lowerLimit': '0.25', 'upperLimit': '2.00'}, {'value': '0.55', 'groupId': 'OG003', 'lowerLimit': '0.50', 'upperLimit': '1.50'}, {'value': '0.50', 'groupId': 'OG004', 'lowerLimit': '0.50', 'upperLimit': '1.50'}, {'value': '0.50', 'groupId': 'OG005', 'lowerLimit': '0.50', 'upperLimit': '1.02'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': 'In the turn of 24 hours after IV midazolam, single dose, administered at day 1,6,17 or after oral midazolam, single dose, administered at days 2, 7 and 18.', 'description': 'tmax =Time of occurrence of Cmax. 13 blood samples were collected at pre-dose and at 2 minutes, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 9, 12 and 24 hours after the administration of IV midazolam, on Days 1, 6 and 17, to determine midazolam and 1-hydroxymidazolam plasma concentrations. 11 blood samples were collected at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 and 24 hours after the administration of oral midazolam, on Days 2, 7 and 18, to determine midazolam and 1-hydroxymidazolam plasma concentrations.', 'unitOfMeasure': 'hours', 'dispersionType': 'Full Range', 'reportingStatus': 'POSTED', 'populationDescription': 'PK population: Part 1 Pharmacokinetic Analysis Population includes all subjects enrolled in Part 1 of the study, who provided evaluable pharmacokinetic data for at least one IMP,'}, {'type': 'PRIMARY', 'title': 'Tmax for Dabigatran (Total and Free), Following Single Doses of the Parent Drug', 'denoms': [{'units': 'Participants', 'counts': [{'value': '26', 'groupId': 'OG000'}, {'value': '26', 'groupId': 'OG001'}, {'value': '26', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': 'Dabigatran Etexilate Alone (Day 1)', 'description': 'Dabigatran etexilate 75 mg, 1 hard capsule, was administered alone.'}, {'id': 'OG001', 'title': 'Dabigatran Etexilate Co-Administered With Givinostat (Day 6)', 'description': 'Dabigatran etexilate 75 mg, 1 hard capsule, was administered 1 hour after the planned morning time of givinostat administration The Potential Inhibitory Effect on day 6 was assessed.'}, {'id': 'OG002', 'title': 'Dabigatran Etexilate Co-Administered With Givinostat (Day 17)', 'description': 'Dabigatran etexilate 75 mg, 1 hard capsule, was administered. The Potential inducing Effect on day 17 was assessed.'}], 'classes': [{'title': 'total dabigatran', 'categories': [{'measurements': [{'value': '2.00', 'groupId': 'OG000', 'lowerLimit': '1.50', 'upperLimit': '4.00'}, {'value': '2.00', 'groupId': 'OG001', 'lowerLimit': '1.00', 'upperLimit': '4.02'}, {'value': '2.00', 'groupId': 'OG002', 'lowerLimit': '1.00', 'upperLimit': '4.00'}]}]}, {'title': 'free dabigatran', 'categories': [{'measurements': [{'value': '2.00', 'groupId': 'OG000', 'lowerLimit': '1.00', 'upperLimit': '4.00'}, {'value': '2.00', 'groupId': 'OG001', 'lowerLimit': '1.50', 'upperLimit': '4.02'}, {'value': '2.00', 'groupId': 'OG002', 'lowerLimit': '1.50', 'upperLimit': '6.00'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': 'In the turn of 72 hours after administration of dabigatran on day 1,6,17', 'description': 'The time of occurrence of maximum observed concentration (tmax) of total dabigatran and free dabigatran following Administration of Dabigatran Etexilate Alone (Day 1) and Co-Administration of Dabigatran Etexilate and Givinostat (Day 6 - Potential Inhibitory Effect, and Day 17 - Potential Inducing Effect).\n\nFifteen (15) blood samples were collected at pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours after the administration of dabigatran etexilate, on Days 1, 6 and 17, for the determination of total and free dabigatran plasma concentrations.', 'unitOfMeasure': 'hours', 'dispersionType': 'Full Range', 'reportingStatus': 'POSTED', 'populationDescription': 'PK population: Part 1 Pharmacokinetic Analysis Population includes all subjects enrolled in Part 1 of the study, who provided evaluable pharmacokinetic data for at least one IMP, without deviations affecting pharmacokinetic interpretation.'}, {'type': 'PRIMARY', 'title': 't1/2 of Midazolam, 1-hydroxymidazolam, Following Single Doses of Givinostat', 'denoms': [{'units': 'Participants', 'counts': [{'value': '26', 'groupId': 'OG000'}, {'value': '26', 'groupId': 'OG001'}, {'value': '26', 'groupId': 'OG002'}, {'value': '26', 'groupId': 'OG003'}, {'value': '26', 'groupId': 'OG004'}, {'value': '26', 'groupId': 'OG005'}]}], 'groups': [{'id': 'OG000', 'title': 'Midazolam IV Alone (Day 1)', 'description': 'A single dose of midazolam 1 mg i.v. was administered.'}, {'id': 'OG001', 'title': 'Midazolam IV Co-administered With Givinostat (Day 6)', 'description': 'Midazolam IV 1 mg/ml, single dose, was co-administered with givinostat Givinostat 10 mg/mL oral suspension was administered once, in the morning in Day 6.'}, {'id': 'OG002', 'title': 'Midazolam IV Co-administered With Givinostat (Day 17)', 'description': 'Midazolam IV 1 mg/ml, single dose, was co-administered with givinostat to study this latter potential inducing effect on midazolam.\n\nFrom the Day 4 to Day 18, Givinostat oral suspension (50 mg) was administered twice a day, in the morning and in the evening.'}, {'id': 'OG003', 'title': 'Oral Midazolam Alone (Day 2)', 'description': 'A single oral dose of midazolam 2.5 mg oral solution was administered alone.'}, {'id': 'OG004', 'title': 'Oral Midazolam Co-Administered With Givinostat (Day 7)', 'description': 'A single oral dose of midazolam 2.5 mg oral solution was administered. The potential Inhibitory Effect of midazolam was assessed .'}, {'id': 'OG005', 'title': 'Oral Midazolam Co-Administered With Givinostat (Day 18)', 'description': 'A single oral dose of midazolam 2.5 mg oral solution was administered. The potential inducing effect of midazolam was assessed.'}], 'classes': [{'title': 'midazolam', 'denoms': [{'units': 'Participants', 'counts': [{'value': '26', 'groupId': 'OG000'}, {'value': '25', 'groupId': 'OG001'}, {'value': '23', 'groupId': 'OG002'}, {'value': '25', 'groupId': 'OG003'}, {'value': '26', 'groupId': 'OG004'}, {'value': '25', 'groupId': 'OG005'}]}], 'categories': [{'measurements': [{'value': '5.27', 'groupId': 'OG000', 'lowerLimit': '4.60', 'upperLimit': '6.04'}, {'value': '5.22', 'groupId': 'OG001', 'lowerLimit': '4.61', 'upperLimit': '5.90'}, {'value': '6.62', 'groupId': 'OG002', 'lowerLimit': '5.83', 'upperLimit': '7.51'}, {'value': '5.48', 'groupId': 'OG003', 'lowerLimit': '4.75', 'upperLimit': '6.32'}, {'value': '5.84', 'groupId': 'OG004', 'lowerLimit': '5.08', 'upperLimit': '6.70'}, {'value': '6.73', 'groupId': 'OG005', 'lowerLimit': '5.89', 'upperLimit': '7.70'}]}]}, {'title': '1-hydroxymidazolam', 'denoms': [{'units': 'Participants', 'counts': [{'value': '26', 'groupId': 'OG000'}, {'value': '25', 'groupId': 'OG001'}, {'value': '23', 'groupId': 'OG002'}, {'value': '25', 'groupId': 'OG003'}, {'value': '24', 'groupId': 'OG004'}, {'value': '25', 'groupId': 'OG005'}]}], 'categories': [{'measurements': [{'value': '4.02', 'groupId': 'OG000', 'lowerLimit': '3.41', 'upperLimit': '4.74'}, {'value': '5.00', 'groupId': 'OG001', 'lowerLimit': '4.20', 'upperLimit': '5.95'}, {'value': '5.74', 'groupId': 'OG002', 'lowerLimit': '4.70', 'upperLimit': '7.03'}, {'value': '4.62', 'groupId': 'OG003', 'lowerLimit': '3.63', 'upperLimit': '5.89'}, {'value': '6.09', 'groupId': 'OG004', 'lowerLimit': '4.76', 'upperLimit': '7.80'}, {'value': '6.43', 'groupId': 'OG005', 'lowerLimit': '5.16', 'upperLimit': '8.01'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'In the turn of 24 hours after IV midazolam, single dose, administered at day 1,6,17 or after oral midazolam, single dose, administered at days 2, 7 and 18.', 'description': 'T1/2 is the Apparent terminal elimination half-life, calculated as ln(2)/λz. t1/2 of midazolam and 1-hydroxymidazolam following Administration of Midazolam IV Alone (Day 1) and Co-Administration of Midazolam IV and Givinostat (Day 6 - Potential Inhibitory Effect, and Day 17 - Potential Inducing Effect) and following Administration of Oral Midazolam Alone (Day 2) and Co-Administration of Oral Midazolam and Givinostat (Day 7 - Potential Inhibitory Effect, and Day 18 - Potential Inducing Effect).\n\n13 blood samples were collected at pre-dose and at 2 minutes, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 9, 12 and 24 hours after the administration of IV midazolam, on Days 1, 6 and 17, to determine midazolam and 1-hydroxymidazolam plasma concentrations. 11 blood samples were collected at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 and 24 hours after the administration of oral midazolam, on Days 2, 7 and 18, to determine midazolam and 1-hydroxymidazolam plasma concentrations.', 'unitOfMeasure': 'hours', 'dispersionType': 'Full Range', 'reportingStatus': 'POSTED', 'populationDescription': 'Pharmacokinetic Analysis includes all subjects enrolled in Part 1 who provided evaluable pk data for at least one IMP. These were: n=26 for (1-Hydroxy)midazolam IV alone, n=25 for (1-Hydroxy)midazolam + givinostat at day 6, n=23 for (1-Hydroxy)midazolam + givinostat at day 17, n=25 for oral (1-Hydroxy)midazolam alone at day 2, n=25 for oral (1-Hydroxy)midazolam + givinostat at day 18 , n=26 for oral midazolam + givinostat at day 7, n=24 for oral 1-Hydroxymidazolam + givinostat at day 7.'}, {'type': 'PRIMARY', 'title': 't1/2 for Dabigatran (Total and Free), Following Single Doses of the Parent Drug', 'denoms': [{'units': 'Participants', 'counts': [{'value': '26', 'groupId': 'OG000'}, {'value': '26', 'groupId': 'OG001'}, {'value': '26', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': 'Dabigatran Etexilate Alone (Day 1)', 'description': 'Dabigatran etexilate 75 mg, 1 hard capsule, was administered alone.'}, {'id': 'OG001', 'title': 'Dabigatran Etexilate Co-Administered With Givinostat (Day 6)', 'description': 'Dabigatran etexilate 75 mg, 1 hard capsule, was administered 1 hour after the planned morning time of givinostat. The Potential Inhibitory Effect on day 6 was assessed.'}, {'id': 'OG002', 'title': 'Dabigatran Etexilate Co-Administered With Givinostat (Day 17)', 'description': 'Dabigatran etexilate 75 mg, 1 hard capsule, was administered 1 hour after the planned morning time of givinostat administration. The Potential inducing Effect on day 17 was assessed.'}], 'classes': [{'title': 'total dabigatran', 'denoms': [{'units': 'Participants', 'counts': [{'value': '26', 'groupId': 'OG000'}, {'value': '26', 'groupId': 'OG001'}, {'value': '26', 'groupId': 'OG002'}]}], 'categories': [{'measurements': [{'value': '7.96', 'groupId': 'OG000', 'lowerLimit': '7.52', 'upperLimit': '8.42'}, {'value': '8.01', 'groupId': 'OG001', 'lowerLimit': '7.21', 'upperLimit': '8.90'}, {'value': '8.74', 'groupId': 'OG002', 'lowerLimit': '8.17', 'upperLimit': '9.36'}]}]}, {'title': 'free dabigatran', 'denoms': [{'units': 'Participants', 'counts': [{'value': '26', 'groupId': 'OG000'}, {'value': '26', 'groupId': 'OG001'}, {'value': '25', 'groupId': 'OG002'}]}], 'categories': [{'measurements': [{'value': '7.28', 'groupId': 'OG000', 'lowerLimit': '6.73', 'upperLimit': '7.89'}, {'value': '7.03', 'groupId': 'OG001', 'lowerLimit': '6.35', 'upperLimit': '7.77'}, {'value': '8.05', 'groupId': 'OG002', 'lowerLimit': '7.30', 'upperLimit': '8.88'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': 'In the turn of 72 hours after administration of dabigatran on day 1,6,17', 'description': 'Apparent terminal elimination half-life, calculated as ln(2)/λz. The t1/2 of total dabigatran and free dabigatran following Administration of Dabigatran Etexilate Alone (Day 1) and Co-Administration of Dabigatran Etexilate and Givinostat (Day 6 - Potential Inhibitory Effect, and Day 17 - Potential Inducing Effect).\n\nFifteen (15) blood samples were collected at pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours after the administration of dabigatran etexilate, on Days 1, 6 and 17, for the determination of total and free dabigatran plasma concentrations.', 'unitOfMeasure': 'hours', 'dispersionType': 'Full Range', 'reportingStatus': 'POSTED', 'populationDescription': 'PK population: Part 1 Pharmacokinetic Analysis Population includes all subjects enrolled in Part 1 of the study, who provided evaluable pharmacokinetic data for at least one IMP, without deviations affecting pharmacokinetic interpretation.'}, {'type': 'PRIMARY', 'title': 'AUC0-t of Midazolam, 1-hydroxymidazolam, Following Single Doses of Givinostat', 'denoms': [{'units': 'Participants', 'counts': [{'value': '26', 'groupId': 'OG000'}, {'value': '26', 'groupId': 'OG001'}, {'value': '26', 'groupId': 'OG002'}, {'value': '26', 'groupId': 'OG003'}, {'value': '26', 'groupId': 'OG004'}, {'value': '26', 'groupId': 'OG005'}]}], 'groups': [{'id': 'OG000', 'title': 'Midazolam IV Alone (Day 1)', 'description': 'A single dose of midazolam 1 mg i.v. was administered on Day 1. Midazolam (and dabigatran etexilate) was administered with the subjects in a semi-recumbent position. Subjects remained semirecumbent until at least 3 hours post-dose.'}, {'id': 'OG001', 'title': 'Midazolam IV Co-administered With Givinostat (Day 6)', 'description': 'Midazolam IV 1 mg/ml, single dose, was co-administered with givinostat (at Day 6) to study this latter potential inhibitory effect on midazolam.'}, {'id': 'OG002', 'title': 'Midazolam IV Co-administered With Givinostat (Day 17)', 'description': 'Midazolam IV 1 mg/ml, single dose, was co-administered with givinostat (at Day 17) to study this latter potential inducing effect on midazolam.'}, {'id': 'OG003', 'title': 'Oral Midazolam Alone (Day 2)', 'description': 'A single oral dose of midazolam 2.5 mg oral solution was administered alone.'}, {'id': 'OG004', 'title': 'Oral Midazolam Co-Administered With Givinostat (Day 7)', 'description': 'A single oral dose of midazolam 2.5 mg oral solution was administered on day 7, 1 hour after the planned morning time of givinostat administration. The potential Inhibitory Effect of midazolam was assessed (day 7)'}, {'id': 'OG005', 'title': 'Oral Midazolam Co-Administered With Givinostat (Day 18)', 'description': 'A single oral dose of midazolam 2.5 mg oral solution was administered on day 18, 1 hour after the planned morning time of givinostat administration. The potential inducing effect of midazolam was assessed (day 18)'}], 'classes': [{'title': 'Midazolam', 'categories': [{'measurements': [{'value': '44094.42', 'groupId': 'OG000', 'lowerLimit': '39998.55', 'upperLimit': '48609.70'}, {'value': '47333.50', 'groupId': 'OG001', 'lowerLimit': '43297.80', 'upperLimit': '51745.35'}, {'value': '53692.16', 'groupId': 'OG002', 'lowerLimit': '48609.52', 'upperLimit': '59306.23'}, {'value': '36483.20', 'groupId': 'OG003', 'lowerLimit': '31064.96', 'upperLimit': '42846.48'}, {'value': '50134.44', 'groupId': 'OG004', 'lowerLimit': '42444.64', 'upperLimit': '59217.42'}, {'value': '57559.53', 'groupId': 'OG005', 'lowerLimit': '49279.79', 'upperLimit': '67230.40'}]}]}, {'title': '1-hydroxymidazolam', 'categories': [{'measurements': [{'value': '5050.60', 'groupId': 'OG000', 'lowerLimit': '4441.81', 'upperLimit': '5742.83'}, {'value': '5362.65', 'groupId': 'OG001', 'lowerLimit': '4757.51', 'upperLimit': '6044.76'}, {'value': '6210.86', 'groupId': 'OG002', 'lowerLimit': '5374.62', 'upperLimit': '7177.22'}, {'value': '10871.00', 'groupId': 'OG003', 'lowerLimit': '9475.99', 'upperLimit': '12471.38'}, {'value': '14264.35', 'groupId': 'OG004', 'lowerLimit': '12357.51', 'upperLimit': '16465.42'}, {'value': '17208.29', 'groupId': 'OG005', 'lowerLimit': '14624.58', 'upperLimit': '20248.46'}]}]}], 'analyses': [{'groupIds': ['OG000', 'OG001'], 'paramType': 'ratio of the geometric LS means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '90', 'paramValue': '107.35', 'ciLowerLimit': '103.35', 'ciUpperLimit': '111.49', 'groupDescription': 'Midazolam: Potential Inhibitory Effect of Givinostat on the Pharmacokinetics of Midazolam IV - AUC0-t', 'nonInferiorityType': 'OTHER', 'nonInferiorityComment': 'GMR corresponds to the ratio of the Geometric LSmeans of Midazolam IV Co-Administered with Givinostat (Day 6) and the Geometric LSmeans of Midazolam of IV Alone (Day 1)'}, {'groupIds': ['OG000', 'OG001'], 'paramType': 'ratio of the Geometric LSmeans', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '90', 'paramValue': '106.18', 'ciLowerLimit': '100.84', 'ciUpperLimit': '111.80', 'groupDescription': '1-Hydroxymidazolam: Potential Inhibitory Effect of Givinostat on the Pharmacokinetics of Midazolam IV - AUC0-t', 'nonInferiorityType': 'OTHER', 'nonInferiorityComment': 'GMR corresponds to the ratio of the Geometric LSmeans of Midazolam IV Co-Administered with Givinostat (Day 6) and the Geometric LSmeans of Midazolam of IV Alone (Day 1)'}, {'groupIds': ['OG000', 'OG002'], 'paramType': 'ratio of the Geometric LSmeans', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '90', 'paramValue': '121.77', 'ciLowerLimit': '117.56', 'ciUpperLimit': '126.12', 'groupDescription': 'Midazolam: Potential Inducing Effect of Givinostat on the Pharmacokinetics of Midazolam IV - AUC0-t', 'nonInferiorityType': 'OTHER', 'nonInferiorityComment': 'GMR corresponds to the ratio of the Geometric LSmeans of Midazolam IV Co-Administered with Givinostat (Day 17) and the Geometric LSmeans of Midazolam of IV Alone (Day 1)'}, {'groupIds': ['OG000', 'OG002'], 'paramType': 'ratio of the Geometric LSmeans', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '90', 'paramValue': '122.97', 'ciLowerLimit': '115.08', 'ciUpperLimit': '131.41', 'groupDescription': '1-Hydroxymidazolam: Potential Inducing Effect of Givinostat on the Pharmacokinetics of Midazolam IV - AUC0-t', 'nonInferiorityType': 'OTHER', 'nonInferiorityComment': 'GMR corresponds to the ratio of the Geometric LSmeans of Midazolam IV Co-Administered with Givinostat (Day 17) and the Geometric LSmeans of Midazolam of IV Alone (Day 1)'}, {'groupIds': ['OG003', 'OG004'], 'paramType': 'ratio of the Geometric LSmeans', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '90', 'paramValue': '137.42', 'ciLowerLimit': '128.09', 'ciUpperLimit': '147.43', 'groupDescription': 'Midazolam: Potential Inhibitory Effect of Givinostat on the Pharmacokinetics of Oral Midazolam - AUC0-t', 'nonInferiorityType': 'OTHER', 'nonInferiorityComment': 'GMR corresponds to the ratio of the Geometric LSmeans of Oral Midazolam Co-Administered with Givinostat (Day 7) and the Geometric LSmeans of Oral Midazolam Alone (Day 2)'}, {'groupIds': ['OG003', 'OG004'], 'paramType': 'ratio of the Geometric LSmeans', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '90', 'paramValue': '131.21', 'ciLowerLimit': '122.47', 'ciUpperLimit': '140.59', 'groupDescription': '1-Hydroxymidazolam: Potential Inhibitory Effect of Givinostat on the Pharmacokinetics of Oral Midazolam - AUC0-t', 'nonInferiorityType': 'OTHER', 'nonInferiorityComment': 'GMR corresponds to the ratio of the Geometric LSmeans of Oral Midazolam Co-Administered with Givinostat (Day 7) and the Geometric LSmeans of Oral Midazolam Alone (Day 2)'}, {'groupIds': ['OG003', 'OG005'], 'paramType': 'ratio of the Geometric LSmeans', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '90', 'paramValue': '157.77', 'ciLowerLimit': '147.49', 'ciUpperLimit': '168.76', 'groupDescription': 'Midazolam: Potential Inducing Effect of Givinostat on the Pharmacokinetics of Oral Midazolam. - AUC0-t', 'nonInferiorityType': 'OTHER', 'nonInferiorityComment': 'GMR corresponds to the ratio of the Geometric LSmeans of Oral Midazolam Co-Administered with Givinostat (Day 18) and the Geometric LSmeans of Oral Midazolam Alone (Day 2)'}, {'groupIds': ['OG003', 'OG005'], 'paramType': 'ratio of the Geometric LSmeans', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '90', 'paramValue': '158.30', 'ciLowerLimit': '145.23', 'ciUpperLimit': '172.54', 'groupDescription': '1-Hydroxymidazolam: Potential Inducing Effect of Givinostat on the Pharmacokinetics of Oral Midazolam: - AUC0-t', 'nonInferiorityType': 'OTHER', 'nonInferiorityComment': 'GMR corresponds to the ratio of the Geometric LSmeans of Oral Midazolam Co-Administered with Givinostat (Day 18) and the Geometric LSmeans of Oral Midazolam Alone (Day 2)'}], 'paramType': 'MEDIAN', 'timeFrame': 'In the turn of 24 hours after IV midazolam, single dose, administered at day 1,6,17 or after oral midazolam, single dose, administered at days 2, 7 and 18.', 'description': 'AUC0-t =area under the curve from time zero to last sampling time with quantifiable concentrations. AUC0-t of midazolam and 1-hydroxymidazolam following Administration of Midazolam IV Alone (Day 1) and Co-Administration of Midazolam IV and Givinostat (Day 6 - Potential Inhibitory Effect, and Day 17 - Potential Inducing Effect) and following Oral Midazolam Alone (Day 2) and Co-Administration of Oral Midazolam and Givinostat (Day 7 - Potential Inhibitory Effect, and Day 18 - Potential Inducing Effect).\n\n13 blood samples were collected at pre-dose and at 2 minutes, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 9, 12 and 24 hours after the administration of IV midazolam, on Days 1, 6 and 17, to determine midazolam and 1-hydroxymidazolam plasma concentrations. 11 blood samples were collected at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 and 24 hours after the administration of oral midazolam, on Days 2, 7 and 18, to determine midazolam and 1-hydroxymidazolam plasma concentrations.', 'unitOfMeasure': 'pg.h/mL', 'dispersionType': 'Full Range', 'reportingStatus': 'POSTED', 'populationDescription': 'PK population: Part 1 Pharmacokinetic Analysis Population includes all subjects enrolled in Part 1 of the study, who provided evaluable pharmacokinetic data for at least one IMP,'}, {'type': 'PRIMARY', 'title': 'AUC0-t for Dabigatran (Total and Free), Following Single Doses of the Parent Drug', 'denoms': [{'units': 'Participants', 'counts': [{'value': '26', 'groupId': 'OG000'}, {'value': '26', 'groupId': 'OG001'}, {'value': '26', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': 'Dabigatran Etexilate Alone (Day 1)', 'description': 'Dabigatran etexilate 75 mg, 1 hard capsule, was administered alone.'}, {'id': 'OG001', 'title': 'Dabigatran Etexilate Co-Administered With Givinostat (Day 6)', 'description': 'Dabigatran etexilate 75 mg, 1 hard capsule, was administered 1 hour after the planned morning time of givinostat administration. The Potential Inhibitory Effect on day 6 was assessed.'}, {'id': 'OG002', 'title': 'Dabigatran Etexilate Co-Administered With Givinostat (Day 17)', 'description': 'Dabigatran etexilate 75 mg, 1 hard capsule, was administered 1 hour after the planned morning time of givinostat administration. The Potential inducing Effect on day 17 was assessed.'}], 'classes': [{'title': 'total dabigatran', 'categories': [{'measurements': [{'value': '552.25', 'groupId': 'OG000', 'lowerLimit': '424.19', 'upperLimit': '718.98'}, {'value': '386.05', 'groupId': 'OG001', 'lowerLimit': '299.12', 'upperLimit': '498.25'}, {'value': '386.23', 'groupId': 'OG002', 'lowerLimit': '306.46', 'upperLimit': '486.78'}]}]}, {'title': 'free dabigatran', 'categories': [{'measurements': [{'value': '460.16', 'groupId': 'OG000', 'lowerLimit': '341.52', 'upperLimit': '620.01'}, {'value': '341.01', 'groupId': 'OG001', 'lowerLimit': '268.24', 'upperLimit': '433.52'}, {'value': '332.71', 'groupId': 'OG002', 'lowerLimit': '268.91', 'upperLimit': '411.66'}]}]}], 'analyses': [{'groupIds': ['OG000', 'OG001'], 'paramType': 'ratio of the Geometric LSmeans', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '90', 'paramValue': '69.90', 'ciLowerLimit': '58.43', 'ciUpperLimit': '83.64', 'groupDescription': 'Total Dabigatran: Potential Inhibitory Effect of Givinostat on the Pharmacokinetics - AUC0-t', 'nonInferiorityType': 'OTHER', 'nonInferiorityComment': 'GMR corresponds to the ratio of the Geometric LSmeans of Dabigatran Etexilate Co-Administered with Givinostat (Day 6) and the Geometric LSmeans of Dabigatran Etexilate Alone (Day 1)'}, {'groupIds': ['OG000', 'OG001'], 'paramType': 'ratio of the Geometric LSmeans', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '90', 'paramValue': '71.43', 'ciLowerLimit': '58.67', 'ciUpperLimit': '86.98', 'groupDescription': 'Free Dabigatran: Potential Inhibitory Effect of Givinostat on the Pharmacokinetics of Dabigatran Etexilate - AUC0-t', 'nonInferiorityType': 'OTHER', 'nonInferiorityComment': 'GMR corresponds to the ratio of the Geometric LSmeans of Dabigatran Etexilate Co-Administered with Givinostat (Day 6) and the Geometric LSmeans of Dabigatran Etexilate Alone (Day 1)'}, {'groupIds': ['OG000', 'OG002'], 'paramType': 'ratio of the Geometric LSmeans', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '90', 'paramValue': '69.94', 'ciLowerLimit': '58.82', 'ciUpperLimit': '83.15', 'groupDescription': 'Total Dabigatran: Potential Inducing Effect of Givinostat on the Pharmacokinetics of Dabigatran Etexilate - AUC0-t', 'nonInferiorityType': 'OTHER', 'nonInferiorityComment': 'GMR corresponds to the ratio of the Geometric LSmeans of Dabigatran Etexilate Co-Administered with Givinostat (Day 17) and the Geometric LSmeans of Dabigatran Etexilate Alone (Day 1)'}, {'groupIds': ['OG000', 'OG002'], 'paramType': 'ratio of the Geometric LSmeans', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '90', 'paramValue': '72.30', 'ciLowerLimit': '59.92', 'ciUpperLimit': '87.25', 'groupDescription': 'Free Dabigatran: Potential Induction Effect of Givinostat on the Pharmacokinetics of Dabigatran Etexilate - AUC0-t', 'nonInferiorityType': 'OTHER', 'nonInferiorityComment': 'GMR corresponds to the ratio of the Geometric LSmeans of Dabigatran Etexilate Co-Administered with Givinostat (Day 17) and the Geometric Lsmeans of Dabigatran Etexilate Alone (Day 1)'}], 'paramType': 'MEDIAN', 'timeFrame': 'In the turn of 72 hours after administration of dabigatran on day 1,6,17', 'description': 'AUC0-t =area under the curve from time zero to last sampling time with quantifiable concentrations. AUC0-t of total dabigatran and free dabigatran following Administration of Dabigatran Etexilate Alone (Day 1) and Co-Administration of Dabigatran Etexilate and Givinostat (Day 6 - Potential Inhibitory Effect, and Day 17 - Potential Inducing Effect).\n\nFifteen (15) blood samples were collected at pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours after the administration of dabigatran etexilate, on Days 1, 6 and 17, for the determination of total and free dabigatran plasma concentrations.', 'unitOfMeasure': 'ng.h/mL', 'dispersionType': 'Full Range', 'reportingStatus': 'POSTED', 'populationDescription': 'PK population: Part 1 Pharmacokinetic Analysis Population includes all subjects enrolled in Part 1 of the study, who provided evaluable pharmacokinetic data for at least one IMP, without deviations affecting pharmacokinetic interpretation.'}, {'type': 'PRIMARY', 'title': 'AUC0-inf of Midazolam, 1-hydroxymidazolam, Following Single Doses of Givinostat', 'denoms': [{'units': 'Participants', 'counts': [{'value': '26', 'groupId': 'OG000'}, {'value': '26', 'groupId': 'OG001'}, {'value': '26', 'groupId': 'OG002'}, {'value': '26', 'groupId': 'OG003'}, {'value': '26', 'groupId': 'OG004'}, {'value': '26', 'groupId': 'OG005'}]}], 'groups': [{'id': 'OG000', 'title': 'Midazolam IV Alone (Day 1)', 'description': 'A single dose of midazolam 1 mg i.v. was administered.'}, {'id': 'OG001', 'title': 'Midazolam IV Co-administered With Givinostat (Day 6)', 'description': 'Midazolam IV 1 mg/ml, single dose, was co-administered with givinostat to study this latter potential inhibitory effect on midazolam.'}, {'id': 'OG002', 'title': 'Midazolam IV Co-administered With Givinostat (Day 17)', 'description': 'Midazolam IV 1 mg/ml, single dose, was co-administered with givinostat to study this latter potential inducing effect on midazolam.'}, {'id': 'OG003', 'title': 'Oral Midazolam Alone (Day 2)', 'description': 'A single oral dose of midazolam 2.5 mg oral solution was administered alone.'}, {'id': 'OG004', 'title': 'Oral Midazolam Co-Administered With Givinostat (Day 7)', 'description': 'A single oral dose of midazolam 2.5 mg oral solution was administered on day 7, 1 hour after the planned morning time of givinostat administration. The potential Inhibitory Effect of midazolam was assessed.'}, {'id': 'OG005', 'title': 'Oral Midazolam Co-Administered With Givinostat (Day 18)', 'description': 'A single oral dose of midazolam 2.5 mg oral solution was administered on day 18, 1 hour after the planned morning time of givinostat administration. The potential inducing effect of midazolam was assessed.'}], 'classes': [{'title': 'Midazolam', 'denoms': [{'units': 'Participants', 'counts': [{'value': '26', 'groupId': 'OG000'}, {'value': '26', 'groupId': 'OG001'}, {'value': '26', 'groupId': 'OG002'}, {'value': '25', 'groupId': 'OG003'}, {'value': '26', 'groupId': 'OG004'}, {'value': '25', 'groupId': 'OG005'}]}], 'categories': [{'measurements': [{'value': '46054.19', 'groupId': 'OG000', 'lowerLimit': '41834.50', 'upperLimit': '50699.50'}, {'value': '49532.66', 'groupId': 'OG001', 'lowerLimit': '45406.00', 'upperLimit': '54034.35'}, {'value': '57112.86', 'groupId': 'OG002', 'lowerLimit': '51342.91', 'upperLimit': '63531.25'}, {'value': '39037.54', 'groupId': 'OG003', 'lowerLimit': '33096.57', 'upperLimit': '46044.94'}, {'value': '53379.48', 'groupId': 'OG004', 'lowerLimit': '45107.58', 'upperLimit': '63168.29'}, {'value': '62904.03', 'groupId': 'OG005', 'lowerLimit': '52906.81', 'upperLimit': '74790.32'}]}]}, {'title': '1-Hydroxymidazolam', 'denoms': [{'units': 'Participants', 'counts': [{'value': '26', 'groupId': 'OG000'}, {'value': '25', 'groupId': 'OG001'}, {'value': '23', 'groupId': 'OG002'}, {'value': '26', 'groupId': 'OG003'}, {'value': '24', 'groupId': 'OG004'}, {'value': '25', 'groupId': 'OG005'}]}], 'categories': [{'measurements': [{'value': '5720.13', 'groupId': 'OG000', 'lowerLimit': '4981.56', 'upperLimit': '6568.21'}, {'value': '6404.39', 'groupId': 'OG001', 'lowerLimit': '5615.24', 'upperLimit': '7304.43'}, {'value': '7821.70', 'groupId': 'OG002', 'lowerLimit': '6736.26', 'upperLimit': '9082.04'}, {'value': '11914.16', 'groupId': 'OG003', 'lowerLimit': '10292.86', 'upperLimit': '13790.84'}, {'value': '15895.61', 'groupId': 'OG004', 'lowerLimit': '13769.86', 'upperLimit': '18349.51'}, {'value': '19199.79', 'groupId': 'OG005', 'lowerLimit': '16300.75', 'upperLimit': '22614.41'}]}]}], 'analyses': [{'groupIds': ['OG000', 'OG001'], 'paramType': 'ratio of the Geometric LSmeans', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '90', 'paramValue': '107.55', 'ciLowerLimit': '103.35', 'ciUpperLimit': '111.49', 'groupDescription': 'Midazolam: Potential Inhibitory Effect of Givinostat on the Pharmacokinetics of Midazolam IV: AUC0-inf', 'nonInferiorityType': 'OTHER', 'nonInferiorityComment': 'GMR corresponds to the ratio of the Geometric LSmeans of Midazolam IV Co-Administered with Givinostat (Day 6) and the Geometric LSmeans of Midazolam of IV Alone (Day 1)'}, {'groupIds': ['OG000', 'OG001'], 'paramType': 'ratio of the Geometric LSmeans', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '90', 'paramValue': '112.17', 'ciLowerLimit': '106.21', 'ciUpperLimit': '118.46', 'groupDescription': '1-Hydroxymidazolam: Potential Inhibitory Effect of Givinostat on the Pharmacokinetics of Midazolam IV - AUC0-inf', 'nonInferiorityType': 'OTHER', 'nonInferiorityComment': 'GMR corresponds to the ratio of the Geometric LSmeans of Midazolam IV Co-Administered with Givinostat (Day 6) and the Geometric LSmeans of Midazolam of IV Alone (Day 1)'}, {'groupIds': ['OG000', 'OG002'], 'paramType': 'ratio of the Geometric LSmeans', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '90', 'paramValue': '124.01', 'ciLowerLimit': '119.44', 'ciUpperLimit': '128.76', 'groupDescription': 'Midazolam: Potential Inducing Effect of Givinostat on the Pharmacokinetics of Midazolam IV - AUC0-inf', 'nonInferiorityType': 'OTHER', 'nonInferiorityComment': 'GMR corresponds to the ratio of the Geometric LSmeans of Midazolam IV Co-Administered with Givinostat (Day 17) and the Geometric LSmeans of Midazolam of IV Alone (Day 1)'}, {'groupIds': ['OG000', 'OG002'], 'paramType': 'ratio of the Geometric LSmeans', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '90', 'paramValue': '134.29', 'ciLowerLimit': '126.15', 'ciUpperLimit': '142.96', 'groupDescription': '1-Hydroxymidazolam: Potential Inducing Effect of Givinostat on the Pharmacokinetics of Midazolam IV. AUC0-inf', 'nonInferiorityType': 'OTHER', 'nonInferiorityComment': 'GMR corresponds to the ratio of the Geometric LSmeans of Midazolam IV Co-Administered with Givinostat (Day 17) and the Geometric LSmeans of Midazolam of IV Alone (Day 1)'}, {'groupIds': ['OG003', 'OG004'], 'paramType': 'ratio of the Geometric LSmeans', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '90', 'paramValue': '138.75', 'ciLowerLimit': '129.05', 'ciUpperLimit': '149.18', 'groupDescription': 'Midazolam: Potential Inhibitory Effect of Givinostat on the Pharmacokinetics of Oral Midazolam - AUC0-inf', 'nonInferiorityType': 'OTHER', 'nonInferiorityComment': 'GMR corresponds to the ratio of the Geometric LSmeans of Oral Midazolam Co-Administered with Givinostat (Day 7) and the Geometric LSmeans of Oral Midazolam Alone (Day 2)'}, {'groupIds': ['OG003', 'OG004'], 'paramType': 'GMR corresponds to the ratio of the Geom', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '90', 'paramValue': '134.18', 'ciLowerLimit': '124.19', 'ciUpperLimit': '144.97', 'groupDescription': '1-Hydroxymidazolam: Potential Inhibitory Effect of Givinostat on the Pharmacokinetics of Oral Midazolam: AUC0-inf', 'nonInferiorityType': 'OTHER'}, {'groupIds': ['OG003', 'OG005'], 'paramType': 'ratio of the Geometric LSmeans', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '90', 'paramValue': '162.76', 'ciLowerLimit': '151.13', 'ciUpperLimit': '175.28', 'groupDescription': 'Midazolam: Potential Inducing Effect of Givinostat on the Pharmacokinetics of Oral Midazolam: AUC0-inf', 'nonInferiorityType': 'OTHER', 'nonInferiorityComment': 'GMR corresponds to the ratio of the Geometric LSmeans of Oral Midazolam Co-Administered with Givinostat (Day 18) and the Geometric LSmeans of Oral Midazolam Alone (Day 2)'}, {'groupIds': ['OG003', 'OG005'], 'paramType': 'ratio of the Geometric LSmeans', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '90', 'paramValue': '161.20', 'ciLowerLimit': '147.80', 'ciUpperLimit': '175.82', 'groupDescription': '1-Hydroxymidazolam: Potential Inducing Effect of Givinostat on the Pharmacokinetics of Oral Midazolam - AUC0-inf', 'nonInferiorityType': 'OTHER', 'nonInferiorityComment': 'GMR corresponds to the ratio of the Geometric LSmeans of Oral Midazolam Co-Administered with Givinostat (Day 18) and the Geometric LSmeans of Oral Midazolam Alone (Day 2)'}], 'paramType': 'MEDIAN', 'timeFrame': 'In the turn of 24 hours after IV midazolam, single dose, administered at day 1,6,17 or after oral midazolam, single dose, administered at days 2, 7 and 18.', 'description': 'AUC0-inf=Total AUC extrapolated to infinity, calculated as AUC0-t + Clast/λz, where Clast is the last measurable concentration and λz is the apparent terminal elimination rate constant.\n\n13 blood samples were collected at pre-dose and at 2 minutes, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 9, 12 and 24 hours after the administration of IV midazolam, on Days 1, 6 and 17, to determine midazolam and 1-hydroxymidazolam plasma concentrations. 11 blood samples were collected at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 and 24 hours after the administration of oral midazolam, on Days 2, 7 and 18, to determine midazolam and 1-hydroxymidazolam plasma concentrations.', 'unitOfMeasure': 'pg.h/mL', 'dispersionType': 'Full Range', 'reportingStatus': 'POSTED', 'populationDescription': 'Pharmacokinetic Analysis includes all subjects enrolled in Part 1 who provided evaluable pk data for at least one IMP. These were:\n\nn=26 for (1-Hydroxy)midazolam IV alone, n=26 for Mid IV + givinostat (G) at days 6 and 17, for oral hydroxymid alone at day 2, oral Mid + G at day 7.\n\nn=25 for 1-Hydroxymid + G at day 6, oral mid alone at day 2, oral (1-Hydroxy)mid + G at day 18.\n\nn=24 for oral 1-Hydroxymid + G at day 7 n=23 for oral 1-hydroxymid + G at day 17'}, {'type': 'PRIMARY', 'title': 'AUC0-inf for Dabigatran (Total and Free), Following Single Doses of the Parent Drug', 'denoms': [{'units': 'Participants', 'counts': [{'value': '26', 'groupId': 'OG000'}, {'value': '26', 'groupId': 'OG001'}, {'value': '26', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': 'Dabigatran Etexilate Alone (Day 1)', 'description': 'Dabigatran etexilate 75 mg, 1 hard capsule, was administered alone.'}, {'id': 'OG001', 'title': 'Dabigatran Etexilate Co-Administered With Givinostat (Day 6)', 'description': 'Dabigatran etexilate 75 mg, 1 hard capsule, was administered 1 hour after the planned morning time of givinostat administration. The Potential Inhibitory Effect was assessed.'}, {'id': 'OG002', 'title': 'Dabigatran Etexilate Co-Administered With Givinostat (Day 17)', 'description': 'Dabigatran etexilate 75 mg, 1 hard capsule, was administered 1 hour after the planned morning time of givinostat administration. The Potential inducing Effect was assessed.'}], 'classes': [{'title': 'total dabigatran', 'denoms': [{'units': 'Participants', 'counts': [{'value': '26', 'groupId': 'OG000'}, {'value': '26', 'groupId': 'OG001'}, {'value': '26', 'groupId': 'OG002'}]}], 'categories': [{'measurements': [{'value': '563.09', 'groupId': 'OG000', 'lowerLimit': '436.43', 'upperLimit': '726.51'}, {'value': '393.93', 'groupId': 'OG001', 'lowerLimit': '306.01', 'upperLimit': '507.11'}, {'value': '396.25', 'groupId': 'OG002', 'lowerLimit': '315.23', 'upperLimit': '498.10'}]}]}, {'title': 'free dabigatran', 'denoms': [{'units': 'Participants', 'counts': [{'value': '26', 'groupId': 'OG000'}, {'value': '26', 'groupId': 'OG001'}, {'value': '25', 'groupId': 'OG002'}]}], 'categories': [{'measurements': [{'value': '467.79', 'groupId': 'OG000', 'lowerLimit': '349.48', 'upperLimit': '626.16'}, {'value': '347.56', 'groupId': 'OG001', 'lowerLimit': '273.95', 'upperLimit': '440.95'}, {'value': '347.73', 'groupId': 'OG002', 'lowerLimit': '280.67', 'upperLimit': '430.81'}]}]}], 'analyses': [{'groupIds': ['OG000', 'OG001'], 'paramType': 'ratio of the Geometric LSmeans', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '90', 'paramValue': '69.96', 'ciLowerLimit': '58.83', 'ciUpperLimit': '83.20', 'groupDescription': 'Total Dabigatran: Potential Inhibitory Effect of Givinostat on the Pharmacokinetics of Dabigatran Etexilate - AUC0-inf', 'nonInferiorityType': 'OTHER', 'nonInferiorityComment': 'GMR corresponds to the ratio of the Geometric LSmeans of Dabigatran Etexilate Co-Administered with Givinostat (Day 6) and the Geometric LSmeans of Dabigatran Etexilate Alone (Day 1)'}, {'groupIds': ['OG000', 'OG001'], 'paramType': 'ratio of the Geometric LSmeans', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '90', 'paramValue': '71.65', 'ciLowerLimit': '59.08', 'ciUpperLimit': '86.88', 'groupDescription': 'Free Dabigatran: Potential Inhibitory Effect of Givinostat on the Pharmacokinetics of Dabigatran Etexilate - AUC0-inf', 'nonInferiorityType': 'OTHER', 'nonInferiorityComment': 'GMR corresponds to the ratio of the Geometric LSmeans of Dabigatran Etexilate Co-Administered with Givinostat (Day 6) and the Geometric LSmeans of Dabigatran Etexilate Alone (Day 1)'}, {'groupIds': ['OG000', 'OG002'], 'paramType': 'ratio of the Geometric LSmeans', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '90', 'paramValue': '70.37', 'ciLowerLimit': '59.64', 'ciUpperLimit': '83.03', 'groupDescription': 'Total Dabigatran: Potential Inducing Effect of Givinostat on the Pharmacokinetics of Dabigatran Etexilate - AUC0-inf', 'nonInferiorityType': 'OTHER', 'nonInferiorityComment': 'GMR corresponds to the ratio of the Geometric LSmeans of Dabigatran Etexilate Co-Administered with Givinostat (Day 17) and the Geometric LSmeans of Dabigatran Etexilate Alone (Day 1)'}, {'groupIds': ['OG000', 'OG002'], 'paramType': 'ratio of the Geometric LSmeans', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '90', 'paramValue': '73.45', 'ciLowerLimit': '60.79', 'ciUpperLimit': '88.75', 'groupDescription': 'Free Dabigatran: Potential Induction Effect of Givinostat on the Pharmacokinetics of Dabigatran Etexilate. AUC0-inf', 'nonInferiorityType': 'OTHER', 'nonInferiorityComment': 'GMR corresponds to the ratio of the Geometric LSmeans of Dabigatran Etexilate Co-Administered with Givinostat (Day 17) and the Geometric Lsmeans of Dabigatran Etexilate Alone (Day 1)'}], 'paramType': 'MEDIAN', 'timeFrame': 'In the turn of 72 hours after administration of dabigatran on day 1,6,17', 'description': 'AUC0-inf = Total AUC extrapolated to infinity, calculated as AUC0-t + Clast/λz, where Clast is the last measurable concentration and λz is the apparent terminal elimination rate constant. AUC0-inf of total dabigatran and free dabigatran following Administration of Dabigatran Etexilate Alone (Day 1) and Co-Administration of Dabigatran Etexilate and Givinostat (Day 6 - Potential Inhibitory Effect, and Day 17 - Potential Inducing Effect).\n\nFifteen (15) blood samples were collected at pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours after the administration of dabigatran etexilate, on Days 1, 6 and 17, for the determination of total and free dabigatran plasma concentrations.', 'unitOfMeasure': 'ng.h/mL', 'dispersionType': 'Full Range', 'reportingStatus': 'POSTED', 'populationDescription': 'PK population: Part 1 Pharmacokinetic Analysis Population includes all subjects enrolled in Part 1 of the study, who provided evaluable pharmacokinetic data for at least one IMP, without deviations affecting pharmacokinetic interpretation.'}, {'type': 'PRIMARY', 'title': '%AUCextrap of Midazolam, 1-hydroxymidazolam, Following Single Doses of Givinostat', 'denoms': [{'units': 'Participants', 'counts': [{'value': '26', 'groupId': 'OG000'}, {'value': '26', 'groupId': 'OG001'}, {'value': '26', 'groupId': 'OG002'}, {'value': '26', 'groupId': 'OG003'}, {'value': '26', 'groupId': 'OG004'}, {'value': '26', 'groupId': 'OG005'}]}], 'groups': [{'id': 'OG000', 'title': 'Midazolam IV Alone (Day 1)', 'description': 'A single dose of midazolam 1 mg i.v. was administered.'}, {'id': 'OG001', 'title': 'Midazolam IV Co-administered With Givinostat (Day 6)', 'description': 'Midazolam IV 1 mg/ml, single dose, was co-administered with givinostat to study this latter potential inhibitory effect on midazolam.'}, {'id': 'OG002', 'title': 'Midazolam IV Co-administered With Givinostat (Day 17)', 'description': 'Midazolam IV 1 mg/ml, single dose, was co-administered with givinostat to study this latter potential inducing effect on midazolam.'}, {'id': 'OG003', 'title': 'Oral Midazolam Alone (Day 2)', 'description': 'A single oral dose of midazolam 2.5 mg oral solution was administered alone.'}, {'id': 'OG004', 'title': 'Oral Midazolam Co-Administered With Givinostat (Day 7)', 'description': 'A single oral dose of midazolam 2.5 mg oral solution was administered on day 7, 1 hour after the planned morning time of givinostat administration. The potential Inhibitory Effect of midazolam was assessed.'}, {'id': 'OG005', 'title': 'Oral Midazolam Co-Administered With Givinostat (Day 18)', 'description': 'A single oral dose of midazolam 2.5 mg oral solution was administered on day 18, 1 hour after the planned morning time of givinostat administration. The potential inducing effect of midazolam was assessed.'}], 'classes': [{'title': 'Midazolam', 'denoms': [{'units': 'Participants', 'counts': [{'value': '26', 'groupId': 'OG000'}, {'value': '26', 'groupId': 'OG001'}, {'value': '26', 'groupId': 'OG002'}, {'value': '25', 'groupId': 'OG003'}, {'value': '26', 'groupId': 'OG004'}, {'value': '25', 'groupId': 'OG005'}]}], 'categories': [{'measurements': [{'value': '3.87', 'groupId': 'OG000', 'lowerLimit': '3.23', 'upperLimit': '4.63'}, {'value': '3.96', 'groupId': 'OG001', 'lowerLimit': '3.27', 'upperLimit': '4.81'}, {'value': '5.12', 'groupId': 'OG002', 'lowerLimit': '4.07', 'upperLimit': '6.43'}, {'value': '5.02', 'groupId': 'OG003', 'lowerLimit': '4.28', 'upperLimit': '5.90'}, {'value': '5.33', 'groupId': 'OG004', 'lowerLimit': '4.31', 'upperLimit': '6.59'}, {'value': '5.79', 'groupId': 'OG005', 'lowerLimit': '4.46', 'upperLimit': '7.52'}]}]}, {'title': '1-Hydroxymidazolam', 'denoms': [{'units': 'Participants', 'counts': [{'value': '26', 'groupId': 'OG000'}, {'value': '25', 'groupId': 'OG001'}, {'value': '23', 'groupId': 'OG002'}, {'value': '26', 'groupId': 'OG003'}, {'value': '26', 'groupId': 'OG004'}, {'value': '26', 'groupId': 'OG005'}]}], 'categories': [{'measurements': [{'value': '9.72', 'groupId': 'OG000', 'lowerLimit': '7.55', 'upperLimit': '12.52'}, {'value': '13.20', 'groupId': 'OG001', 'lowerLimit': '10.09', 'upperLimit': '17.27'}, {'value': '15.97', 'groupId': 'OG002', 'lowerLimit': '12.14', 'upperLimit': '21.02'}, {'value': '6.95', 'groupId': 'OG003', 'lowerLimit': '5.18', 'upperLimit': '9.33'}, {'value': '8.42', 'groupId': 'OG004', 'lowerLimit': '6.62', 'upperLimit': '10.70'}, {'value': '8.80', 'groupId': 'OG005', 'lowerLimit': '7.42', 'upperLimit': '10.44'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': 'In the turn of 24 hours after IV midazolam, single dose, administered at day 1,6,17 or after oral midazolam, single dose, administered at days 2, 7 and 18.', 'description': 'Area under the curve or AUC is a pharmacokinetic statistic used to describe the total exposure to a drug. More specifically, it is the time-averaged concentration of drug circulating in the body fluid analyzed (normally plasma, blood or serum). Standard calculation of AUC involves using non-compartmental techniques to calculate the AUC from time 0 to the last measurable concentration. This is called AUC0-t and represents the observed exposure to a drug. The total AUC or AUC0-∞ is the area under the curve from time 0 extrapolated to infinite time.\n\n%AUCextrap = Percentage of AUC0-∞ due to extrapolation from the time of the last measurable concentration (tlast) to infinity, i.e., residual area, calculated as 100 ∙(AUC0-∞ - AUC0-t) / AUC0-∞.', 'unitOfMeasure': 'Percentage of AUC0-inf', 'dispersionType': 'Full Range', 'reportingStatus': 'POSTED', 'populationDescription': 'PK population: Part 1 Pharmacokinetic Analysis Population includes all subjects enrolled in Part 1 of the study, who provided evaluable pharmacokinetic data for at least one IMP,'}, {'type': 'PRIMARY', 'title': '%AUC0extrap (%) for Dabigatran (Total and Free), Following Single Doses of the Parent Drug', 'denoms': [{'units': 'Participants', 'counts': [{'value': '26', 'groupId': 'OG000'}, {'value': '26', 'groupId': 'OG001'}, {'value': '26', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': 'Dabigatran Etexilate Alone (Day 1)', 'description': 'Dabigatran etexilate 75 mg, 1 hard capsule, was administered alone.'}, {'id': 'OG001', 'title': 'Dabigatran Etexilate Co-Administered With Givinostat (Day 6)', 'description': 'Dabigatran etexilate 75 mg, 1 hard capsule, was administered 1 hour after the planned morning time of givinostat administration. The Potential Inhibitory Effect was assessed.'}, {'id': 'OG002', 'title': 'Dabigatran Etexilate Co-Administered With Givinostat (Day 17)', 'description': 'Dabigatran etexilate 75 mg, 1 hard capsule, was administered 1 hour after the planned morning time of givinostat administration. The potential inducing effect was assessed.'}], 'classes': [{'title': 'total dabigatran', 'denoms': [{'units': 'Participants', 'counts': [{'value': '26', 'groupId': 'OG000'}, {'value': '26', 'groupId': 'OG001'}, {'value': '26', 'groupId': 'OG002'}]}], 'categories': [{'measurements': [{'value': '1.37', 'groupId': 'OG000', 'lowerLimit': '1.04', 'upperLimit': '1.80'}, {'value': '1.79', 'groupId': 'OG001', 'lowerLimit': '1.50', 'upperLimit': '2.15'}, {'value': '2.23', 'groupId': 'OG002', 'lowerLimit': '1.84', 'upperLimit': '2.70'}]}]}, {'title': 'free dabigatran', 'denoms': [{'units': 'Participants', 'counts': [{'value': '26', 'groupId': 'OG000'}, {'value': '26', 'groupId': 'OG001'}, {'value': '25', 'groupId': 'OG002'}]}], 'categories': [{'measurements': [{'value': '1.27', 'groupId': 'OG000', 'lowerLimit': '1.00', 'upperLimit': '1.62'}, {'value': '1.69', 'groupId': 'OG001', 'lowerLimit': '1.39', 'upperLimit': '2.05'}, {'value': '2.02', 'groupId': 'OG002', 'lowerLimit': '1.58', 'upperLimit': '2.58'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': 'In the turn of 72 hours after administration of dabigatran on day 1,6,17', 'description': 'Area under the curve (AUC) is a pharmacokinetic statistic used to describe the total exposure to a drug. More specifically, it is the time-averaged concentration of drug circulating in the body fluid analyzed. The total AUC (AUC0-∞) is the area under the curve from time 0 extrapolated to infinite time.\n\n* AUC0extrap = Percentage of AUC0-∞ due to extrapolation from the time of the last measurable concentration (tlast) to infinity, i.e., residual area, calculated as 100 ∙(AUC0-∞ - AUC0-t) / AUC0-∞.\n* AUC0extrap of total dabigatran and free dabigatran following Administration of Dabigatran Etexilate Alone (Day 1) and Co-Administration of Dabigatran Etexilate and Givinostat (Day 6 - Potential Inhibitory Effect, and Day 17 - Potential Inducing Effect).\n\nFifteen (15) blood samples were collected at pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours after the administration of dabigatran etexilate, on Days 1, 6 and 17, for the determination of total and free dabigatra', 'unitOfMeasure': 'Percentage of AUC0-inf', 'dispersionType': 'Full Range', 'reportingStatus': 'POSTED', 'populationDescription': 'PK population: Part 1 Pharmacokinetic Analysis Population includes all subjects enrolled in Part 1 of the study, who provided evaluable pharmacokinetic data for at least one IMP, without deviations affecting pharmacokinetic interpretation.'}, {'type': 'PRIMARY', 'title': 'λz of Midazolam, 1-hydroxymidazolam, Following Single Doses of Givinostat', 'denoms': [{'units': 'Participants', 'counts': [{'value': '26', 'groupId': 'OG000'}, {'value': '26', 'groupId': 'OG001'}, {'value': '26', 'groupId': 'OG002'}, {'value': '26', 'groupId': 'OG003'}, {'value': '26', 'groupId': 'OG004'}, {'value': '26', 'groupId': 'OG005'}]}], 'groups': [{'id': 'OG000', 'title': 'Midazolam IV Alone (Day 1)', 'description': 'A single dose of midazolam 1 mg i.v. was administered.'}, {'id': 'OG001', 'title': 'Midazolam IV Co-administered With Givinostat (Day 6)', 'description': 'Midazolam IV 1 mg/ml, single dose, was co-administered with givinostat to study this latter potential inhibitory effect on midazolam.'}, {'id': 'OG002', 'title': 'Midazolam IV Co-administered With Givinostat (Day 17)', 'description': 'Midazolam IV 1 mg/ml, single dose, was co-administered with givinostat to study this latter potential inducing effect on midazolam.'}, {'id': 'OG003', 'title': 'Oral Midazolam Alone (Day 2)', 'description': 'A single oral dose of midazolam 2.5 mg oral solution was administered alone.'}, {'id': 'OG004', 'title': 'Oral Midazolam Co-Administered With Givinostat (Day 7)', 'description': 'A single oral dose of midazolam 2.5 mg oral solution was administered on day 7, 1 hour after the planned morning time of givinostat administration. The potential Inhibitory effect of midazolam was assessed.'}, {'id': 'OG005', 'title': 'Oral Midazolam Co-Administered With Givinostat (Day 18)', 'description': 'A single oral dose of midazolam 2.5 mg oral solution was administered on day 18, 1 hour after the planned morning time of givinostat administration. The potential inducing effect of midazolam was assessed.'}], 'classes': [{'title': 'Midazolam', 'denoms': [{'units': 'Participants', 'counts': [{'value': '26', 'groupId': 'OG000'}, {'value': '26', 'groupId': 'OG001'}, {'value': '26', 'groupId': 'OG002'}, {'value': '25', 'groupId': 'OG003'}, {'value': '26', 'groupId': 'OG004'}, {'value': '25', 'groupId': 'OG005'}]}], 'categories': [{'measurements': [{'value': '0.131', 'groupId': 'OG000', 'lowerLimit': '0.115', 'upperLimit': '0.151'}, {'value': '0.133', 'groupId': 'OG001', 'lowerLimit': '0.118', 'upperLimit': '0.150'}, {'value': '0.105', 'groupId': 'OG002', 'lowerLimit': '0.092', 'upperLimit': '0.119'}, {'value': '0.127', 'groupId': 'OG003', 'lowerLimit': '0.110', 'upperLimit': '0.146'}, {'value': '0.119', 'groupId': 'OG004', 'lowerLimit': '0.103', 'upperLimit': '0.136'}, {'value': '0.103', 'groupId': 'OG005', 'lowerLimit': '0.090', 'upperLimit': '0.118'}]}]}, {'title': '1-Hydroxymidazolam', 'denoms': [{'units': 'Participants', 'counts': [{'value': '26', 'groupId': 'OG000'}, {'value': '25', 'groupId': 'OG001'}, {'value': '23', 'groupId': 'OG002'}, {'value': '26', 'groupId': 'OG003'}, {'value': '24', 'groupId': 'OG004'}, {'value': '25', 'groupId': 'OG005'}]}], 'categories': [{'measurements': [{'value': '0.172', 'groupId': 'OG000', 'lowerLimit': '0.146', 'upperLimit': '0.203'}, {'value': '0.139', 'groupId': 'OG001', 'lowerLimit': '0.116', 'upperLimit': '0.165'}, {'value': '0.121', 'groupId': 'OG002', 'lowerLimit': '0.099', 'upperLimit': '0.148'}, {'value': '0.150', 'groupId': 'OG003', 'lowerLimit': '0.118', 'upperLimit': '0.191'}, {'value': '0.114', 'groupId': 'OG004', 'lowerLimit': '0.089', 'upperLimit': '0.146'}, {'value': '0.108', 'groupId': 'OG005', 'lowerLimit': '0.087', 'upperLimit': '0.134'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': 'In the turn of 24 hours after IV midazolam, single dose, administered at day 1,6,17 or after oral midazolam, single dose, administered at days 2, 7 and 18.', 'description': 'Apparent first order elimination rate constant associated with the terminal (log-linear) portion of the concentration versus time curve. The parameter is estimated by linear least square regression analysis using the last three (or more) non-zero concentrations.\n\n13 blood samples were collected at pre-dose and at 2 minutes, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 9, 12 and 24 hours after the administration of IV midazolam, on Days 1, 6 and 17, to determine midazolam and 1-hydroxymidazolam plasma concentrations. 11 blood samples were collected at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 and 24 hours after the administration of oral midazolam, on Days 2, 7 and 18, to determine midazolam and 1-hydroxymidazolam plasma concentrations.', 'unitOfMeasure': '1/h', 'dispersionType': 'Full Range', 'reportingStatus': 'POSTED', 'populationDescription': 'Pharmacokinetic Analysis includes all subjects enrolled in Part 1 who provided evaluable pk data for at least one IMP. These were:\n\nn=26 for (1-Hydroxy)midazolam IV alone, n=26 for Mid IV + givinostat (G) at days 6 and 17, for oral hydroxymid alone at day 2, oral Mid + G at day 7.\n\nn=25 for 1-Hydroxymid + G at day 6, oral mid alone at day 2, oral (1-Hydroxy)mid + G at day 18.\n\nn=24 for oral 1-Hydroxymid + G at day 7 n=23 for IV 1-hydroxymid + G at day 17'}, {'type': 'PRIMARY', 'title': 'λz of Dabigatran (Total and Free), Following Single Doses of Givinostat', 'denoms': [{'units': 'Participants', 'counts': [{'value': '26', 'groupId': 'OG000'}, {'value': '26', 'groupId': 'OG001'}, {'value': '26', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': 'Dabigatran Etexilate Alone (Day 1)', 'description': 'Dabigatran etexilate 75 mg, 1 hard capsule, was administered alone.'}, {'id': 'OG001', 'title': 'Dabigatran Etexilate Co-Administered With Givinostat (Day 6)', 'description': 'Dabigatran etexilate 75 mg, 1 hard capsule, was administered 1 hour after the planned morning time of givinostat administration. The potential inhibitory effect was assessed.'}, {'id': 'OG002', 'title': 'Dabigatran Etexilate Co-Administered With Givinostat (Day 17)', 'description': 'Dabigatran etexilate 75 mg, 1 hard capsule, was administered 1 hour after the planned morning time of givinostat administration. The potential inducing effect was assessed.'}], 'classes': [{'title': 'Total Dabigatran', 'denoms': [{'units': 'Participants', 'counts': [{'value': '26', 'groupId': 'OG000'}, {'value': '26', 'groupId': 'OG001'}, {'value': '26', 'groupId': 'OG002'}]}], 'categories': [{'measurements': [{'value': '0.087', 'groupId': 'OG000', 'lowerLimit': '0.082', 'upperLimit': '0.092'}, {'value': '0.087', 'groupId': 'OG001', 'lowerLimit': '0.078', 'upperLimit': '0.096'}, {'value': '0.079', 'groupId': 'OG002', 'lowerLimit': '0.074', 'upperLimit': '0.085'}]}]}, {'title': 'Free dabigatran', 'denoms': [{'units': 'Participants', 'counts': [{'value': '26', 'groupId': 'OG000'}, {'value': '26', 'groupId': 'OG001'}, {'value': '25', 'groupId': 'OG002'}]}], 'categories': [{'measurements': [{'value': '0.095', 'groupId': 'OG000', 'lowerLimit': '0.088', 'upperLimit': '0.103'}, {'value': '0.099', 'groupId': 'OG001', 'lowerLimit': '0.089', 'upperLimit': '0.109'}, {'value': '0.086', 'groupId': 'OG002', 'lowerLimit': '0.078', 'upperLimit': '0.095'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': 'In the turn of 24 hours after IV midazolam, single dose, administered at day 1,6,17 or after oral midazolam, single dose, administered at days 2, 7 and 18.', 'description': 'Apparent first order elimination rate constant associated with the terminal (log-linear) portion of the concentration versus time curve. The parameter is estimated by linear least square regression analysis using the last three (or more) non-zero concentrations.\n\nFifteen (15) blood samples were collected at pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours after the administration of dabigatran etexilate, on Days 1, 6 and 17, for the determination of total and free dabigatran plasma concentrations.', 'unitOfMeasure': '1/h', 'dispersionType': 'Full Range', 'reportingStatus': 'POSTED', 'populationDescription': 'PK population: Part 1 Pharmacokinetic Analysis Population includes all subjects enrolled in Part 1 of the study, who provided evaluable pharmacokinetic data for at least one IMP,'}, {'type': 'SECONDARY', 'title': 'Number of Adverse Events by Severity (Mild, Moderate, Severe)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '26', 'groupId': 'OG000'}, {'value': '26', 'groupId': 'OG001'}, {'value': '26', 'groupId': 'OG002'}, {'value': '26', 'groupId': 'OG003'}]}], 'groups': [{'id': 'OG000', 'title': 'Midazolam', 'description': 'Oral or IV, alone or in combination'}, {'id': 'OG001', 'title': 'Dabigatran', 'description': 'Dabigatran etexilate 75 mg oral hard capsules in combination with Midazolam'}, {'id': 'OG002', 'title': 'Givinostat', 'description': 'ITF2357/Givinostat\\* 10 mg/mL oral suspension'}, {'id': 'OG003', 'title': 'Total', 'description': '26 participants overall, despite the Investigational Products Dose and Mode of Administration'}], 'classes': [{'title': 'AE mild severity', 'categories': [{'measurements': [{'value': '28', 'groupId': 'OG000'}, {'value': '25', 'groupId': 'OG001'}, {'value': '74', 'groupId': 'OG002'}, {'value': '127', 'groupId': 'OG003'}]}]}, {'title': 'AE moderate severity', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}, {'value': '2', 'groupId': 'OG002'}, {'value': '2', 'groupId': 'OG003'}]}]}, {'title': 'AE severe', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}, {'value': '0', 'groupId': 'OG002'}, {'value': '0', 'groupId': 'OG003'}]}]}], 'paramType': 'NUMBER', 'timeFrame': 'Throughout the study and 10-14 days after the EoS (follow-up visit), i.e. up to date 30-34', 'description': 'An AE was considered as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily imply a causal relationship with this treatment. An AE can, therefore, be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.\n\nThe period of observation for the collection of medical occurrences extended from the time when the subject gave Informed Consent until the follow-up visit.', 'unitOfMeasure': 'number of TEAE', 'reportingStatus': 'POSTED', 'populationDescription': 'All subjects who receive at least one dose of an IMP in Part 1 of the study constitute the Part 1 Safety Analysis Population.'}, {'type': 'SECONDARY', 'title': 'Incidence of Patients With at Least One Adverse Events by Severity (Mild, Moderate, Severe)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '26', 'groupId': 'OG000'}, {'value': '26', 'groupId': 'OG001'}, {'value': '26', 'groupId': 'OG002'}, {'value': '26', 'groupId': 'OG003'}]}], 'groups': [{'id': 'OG000', 'title': 'Midazolam', 'description': 'Oral or IV, alone or in combination'}, {'id': 'OG001', 'title': 'Dabigatran', 'description': 'Dabigatran etexilate 75 mg oral hard capsules in combination with Midazolam'}, {'id': 'OG002', 'title': 'Givinostat', 'description': 'ITF2357/Givinostat\\* 10 mg/mL oral suspension'}, {'id': 'OG003', 'title': 'Total', 'description': '26 participants overall, despite the Investigational Products Dose and Mode of Administration'}], 'classes': [{'title': 'AE mild severity', 'categories': [{'measurements': [{'value': '26', 'groupId': 'OG000'}, {'value': '26', 'groupId': 'OG001'}, {'value': '26', 'groupId': 'OG002'}, {'value': '26', 'groupId': 'OG003'}]}]}, {'title': 'AE moderate severity', 'categories': [{'measurements': [{'value': '2', 'groupId': 'OG000'}, {'value': '2', 'groupId': 'OG001'}, {'value': '2', 'groupId': 'OG002'}, {'value': '2', 'groupId': 'OG003'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': 'During the study and 10-14 days after the EoS (follow-up visit), i.e. up to day 30-34', 'description': 'An AE was considered as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily imply a causal relationship with this treatment. An AE can, therefore, be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.\n\nThe period of observation for the collection of medical occurrences extended from the time when the subject gave Informed Consent until the follow-up visit.', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED', 'populationDescription': 'All subjects who receive at least one dose of an IMP in Part 1 of the study constitute the Part 1 Safety Analysis Population.'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'All Study Participants (SAF and PK Population)', 'description': 'Twenty-six (26) subjects (7 women and 19 men) were admitted to study Part 1:\n\n* single doses of midazolam 1 mg IV + dabigatran etexilate 75 mg were administered 1 hour after the planned morning time of givinostat administration on Days 1, 6 and 17.\n* a single oral dose of midazolam 2.5 mg oral solution was administered 1 hour after the planned morning time of givinostat administration on Days 2, 7 and 18, Please note that From Day 4 to Day 18, givinostat 50 mg as oral suspension was administered twice a day, in the morning and in the evening, while on Day 19 only the morning dose was administered.\n\nMidazolam and dabigatran etexilate were administered following an overnight fasting of at least 8 hours and subjects remained fasted until at least 3 hours post-dose and were administered with the subjects in a semi-recumbent position. Subjects remained semirecumbent until at least 3 hours post-dose. Oral midazolam and dabigatran etexilate were administered with 150 mL of water. No other fluids were allowed from 1 hour before midazolam and dabigatran dosing until 2 hours postdose.\n\nWater was provided ad libitum at all other times.'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '26'}]}, {'type': 'Day 1 - Midazolam (IV) 1 mg + Dabigatran 75 mg', 'comment': 'Potential Inhibitory Effect of Givinostat on Midazolam IV and on Dabigatran Analysis Population', 'achievements': [{'groupId': 'FG000', 'numSubjects': '26'}]}, {'type': 'Day 2 - Midazolam (Oral) 2.5 mg', 'comment': 'Potential inhibitory effect of Givinostat analysis population', 'achievements': [{'groupId': 'FG000', 'numSubjects': '26'}]}, {'type': 'Days 4-5 - Givinostat 50 mg b.i.d.', 'achievements': [{'groupId': 'FG000', 'numSubjects': '26'}]}, {'type': 'Day 6 - Midazolam (IV) 1 mg + Dabigatran 75 mg + Givinostat 50 mg b.i.d.', 'comment': 'Potential Inhibitory Effect of Givinostat on Midazolam IV and on Dabigatran Analysis Population', 'achievements': [{'groupId': 'FG000', 'numSubjects': '26'}]}, {'type': 'Day 7 - Midazolam (Oral) 2.5 mg + Givinostat 50 mg b.i.d.', 'comment': 'Potential Inhibitory Effect of Givinostat analysis population', 'achievements': [{'groupId': 'FG000', 'numSubjects': '26'}]}, {'type': 'Days 8-16 - Givinostat 50 mg b.i.d.', 'achievements': [{'groupId': 'FG000', 'numSubjects': '26'}]}, {'type': 'Day 17 - Midazolam (IV) 1 mg + Dabigatran 75 mg + Givinostat 50 mg b.i.d.', 'comment': 'Potential Inducing Effect of Givinostat on Midazolam IV and on Dabigatran Analysis Population.', 'achievements': [{'groupId': 'FG000', 'numSubjects': '26'}]}, {'type': 'Day 18 - Midazolam (Oral) 2.5 mg + Givinostat 50 mg b.i.d.', 'comment': 'Potential Inducing Effect of Givinostat on Oral Midazolam Analysis Population.', 'achievements': [{'groupId': 'FG000', 'numSubjects': '26'}]}, {'type': 'Day 19 - Givinostat 50 mg', 'achievements': [{'groupId': 'FG000', 'numSubjects': '26'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '26'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}]}]}], 'recruitmentDetails': 'Subjects were screened between Days -21 to -3 (both inclusive) of study part 1 to confirm that they met the subject selection criteria. Prior to any screening assessment, the Investigator (or an appropriate delegate) obtained informed consent from each subject in accordance with the procedures. 26 subjects were enrolled to study part 1. Please note that the overall figure n=104 is wrong; the system in fact automatically and inappropriately sums up the number of each IMP group.'}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '26', 'groupId': 'BG000'}]}], 'groups': [{'id': 'BG000', 'title': 'Number of Subjects Enrolled', 'description': 'Twenty-six (26) subjects (7 women and 19 men) were admitted to study Part 1.'}], 'measures': [{'title': 'Age, Categorical', 'classes': [{'categories': [{'title': '<=18 years', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Between 18 and 65 years', 'measurements': [{'value': '26', 'groupId': 'BG000'}]}, {'title': '>=65 years', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '34', 'spread': '8.2', 'groupId': 'BG000'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '7', 'groupId': 'BG000'}]}, {'title': 'Male', 'measurements': [{'value': '19', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Race (NIH/OMB)', 'classes': [{'categories': [{'title': 'American Indian or Alaska Native', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Asian', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Native Hawaiian or Other Pacific Islander', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Black or African American', 'measurements': [{'value': '1', 'groupId': 'BG000'}]}, {'title': 'White', 'measurements': [{'value': '22', 'groupId': 'BG000'}]}, {'title': 'More than one race', 'measurements': [{'value': '3', 'groupId': 'BG000'}]}, {'title': 'Unknown or Not Reported', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Region of Enrollment', 'classes': [{'title': 'Portugal', 'categories': [{'measurements': [{'value': '26', 'groupId': 'BG000'}]}]}], 'paramType': 'NUMBER', 'unitOfMeasure': 'participants'}], 'populationDescription': 'Pharmacokinetic Analysis Population:Twenty-six (26) subjects were enrolled in Part 1 of the study and provided evaluable pharmacokinetic data for at least one IMP, without deviations affecting pharmacokinetic interpretation.'}}, 'documentSection': {'largeDocumentModule': {'largeDocs': [{'date': '2021-11-29', 'size': 10287176, 'label': 'Study Protocol', 'hasIcf': False, 'hasSap': False, 'filename': 'Prot_000.pdf', 'typeAbbrev': 'Prot', 'uploadDate': '2023-04-11T13:40', 'hasProtocol': True}, {'date': '2022-03-24', 'size': 16366831, 'label': 'Statistical Analysis Plan', 'hasIcf': False, 'hasSap': True, 'filename': 'SAP_001.pdf', 'typeAbbrev': 'SAP', 'uploadDate': '2023-04-11T13:39', 'hasProtocol': False}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE', 'maskingDescription': 'The study was conducted as open label. Blinding procedures were not applicable'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SINGLE_GROUP', 'interventionModelDescription': 'An Open-label, Single-center trial in Healthy Subjects'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 26}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2022-03-21', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2024-12', 'completionDateStruct': {'date': '2022-05-24', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2024-12-23', 'studyFirstSubmitDate': '2022-06-09', 'resultsFirstSubmitDate': '2023-04-26', 'studyFirstSubmitQcDate': '2022-08-04', 'lastUpdatePostDateStruct': {'date': '2025-01-06', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2024-12-23', 'studyFirstPostDateStruct': {'date': '2022-08-08', 'type': 'ACTUAL'}, 'resultsFirstPostDateStruct': {'date': '2025-01-06', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2022-05-08', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Cmax for Midazolam, 1-hydroxymidazolam, Following Single Doses of the Parent Drug', 'timeFrame': 'In the turn of 24 hours after IV midazolam, single dose, administered at day 1,6,17 or after oral midazolam, single dose, administered at days 2, 7 and 18.', 'description': 'Maximum observed plasma concentration (Cmax) of midazolam and 1-hydroxymidazolam following Administration of Midazolam IV Alone (Day 1) and Co-Administration of Midazolam IV and Givinostat (Day 6 - Potential Inhibitory Effect, and Day 17 - Potential Inducing Effect) and following Administration of Oral Midazolam Alone (Day 2) and Co-Administration of Oral Midazolam and Givinostat (Day 7 - Potential Inhibitory Effect, and Day 18 - Potential Inducing Effect).\n\n13 blood samples were collected at pre-dose and at 2 minutes, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 9, 12 and 24 hours after the administration of IV midazolam, on Days 1, 6 and 17, to determine midazolam and 1-hydroxymidazolam plasma concentrations. 11 blood samples were collected at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 and 24 hours after the administration of oral midazolam, on Days 2, 7 and 18, to determine midazolam and 1-hydroxymidazolam plasma concentrations.'}, {'measure': 'Cmax for Dabigatran (Total and Free), Following Single Doses of the Parent Drug', 'timeFrame': 'In the turn of 72 hours after administration of dabigatran on day 1,6,17', 'description': 'Maximum observed plasma concentration (Cmax) of total dabigatran and free dabigatran following Administration of Dabigatran Etexilate Alone (Day 1) and Co-Administration of Dabigatran Etexilate and Givinostat (Day 6 - Potential Inhibitory Effect, and Day 17 - Potential Inducing Effect).\n\nFifteen (15) blood samples were collected in K2-EDTA collection tubes at pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours after the administration of dabigatran etexilate, on Days 1, 6 and 17, for the determination of total and free dabigatran plasma concentrations.'}, {'measure': 'Tmax for Midazolam, 1-hydroxymidazolam, Following Single Doses of the Parent Drug', 'timeFrame': 'In the turn of 24 hours after IV midazolam, single dose, administered at day 1,6,17 or after oral midazolam, single dose, administered at days 2, 7 and 18.', 'description': 'tmax =Time of occurrence of Cmax. 13 blood samples were collected at pre-dose and at 2 minutes, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 9, 12 and 24 hours after the administration of IV midazolam, on Days 1, 6 and 17, to determine midazolam and 1-hydroxymidazolam plasma concentrations. 11 blood samples were collected at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 and 24 hours after the administration of oral midazolam, on Days 2, 7 and 18, to determine midazolam and 1-hydroxymidazolam plasma concentrations.'}, {'measure': 'Tmax for Dabigatran (Total and Free), Following Single Doses of the Parent Drug', 'timeFrame': 'In the turn of 72 hours after administration of dabigatran on day 1,6,17', 'description': 'The time of occurrence of maximum observed concentration (tmax) of total dabigatran and free dabigatran following Administration of Dabigatran Etexilate Alone (Day 1) and Co-Administration of Dabigatran Etexilate and Givinostat (Day 6 - Potential Inhibitory Effect, and Day 17 - Potential Inducing Effect).\n\nFifteen (15) blood samples were collected at pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours after the administration of dabigatran etexilate, on Days 1, 6 and 17, for the determination of total and free dabigatran plasma concentrations.'}, {'measure': 't1/2 of Midazolam, 1-hydroxymidazolam, Following Single Doses of Givinostat', 'timeFrame': 'In the turn of 24 hours after IV midazolam, single dose, administered at day 1,6,17 or after oral midazolam, single dose, administered at days 2, 7 and 18.', 'description': 'T1/2 is the Apparent terminal elimination half-life, calculated as ln(2)/λz. t1/2 of midazolam and 1-hydroxymidazolam following Administration of Midazolam IV Alone (Day 1) and Co-Administration of Midazolam IV and Givinostat (Day 6 - Potential Inhibitory Effect, and Day 17 - Potential Inducing Effect) and following Administration of Oral Midazolam Alone (Day 2) and Co-Administration of Oral Midazolam and Givinostat (Day 7 - Potential Inhibitory Effect, and Day 18 - Potential Inducing Effect).\n\n13 blood samples were collected at pre-dose and at 2 minutes, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 9, 12 and 24 hours after the administration of IV midazolam, on Days 1, 6 and 17, to determine midazolam and 1-hydroxymidazolam plasma concentrations. 11 blood samples were collected at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 and 24 hours after the administration of oral midazolam, on Days 2, 7 and 18, to determine midazolam and 1-hydroxymidazolam plasma concentrations.'}, {'measure': 't1/2 for Dabigatran (Total and Free), Following Single Doses of the Parent Drug', 'timeFrame': 'In the turn of 72 hours after administration of dabigatran on day 1,6,17', 'description': 'Apparent terminal elimination half-life, calculated as ln(2)/λz. The t1/2 of total dabigatran and free dabigatran following Administration of Dabigatran Etexilate Alone (Day 1) and Co-Administration of Dabigatran Etexilate and Givinostat (Day 6 - Potential Inhibitory Effect, and Day 17 - Potential Inducing Effect).\n\nFifteen (15) blood samples were collected at pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours after the administration of dabigatran etexilate, on Days 1, 6 and 17, for the determination of total and free dabigatran plasma concentrations.'}, {'measure': 'AUC0-t of Midazolam, 1-hydroxymidazolam, Following Single Doses of Givinostat', 'timeFrame': 'In the turn of 24 hours after IV midazolam, single dose, administered at day 1,6,17 or after oral midazolam, single dose, administered at days 2, 7 and 18.', 'description': 'AUC0-t =area under the curve from time zero to last sampling time with quantifiable concentrations. AUC0-t of midazolam and 1-hydroxymidazolam following Administration of Midazolam IV Alone (Day 1) and Co-Administration of Midazolam IV and Givinostat (Day 6 - Potential Inhibitory Effect, and Day 17 - Potential Inducing Effect) and following Oral Midazolam Alone (Day 2) and Co-Administration of Oral Midazolam and Givinostat (Day 7 - Potential Inhibitory Effect, and Day 18 - Potential Inducing Effect).\n\n13 blood samples were collected at pre-dose and at 2 minutes, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 9, 12 and 24 hours after the administration of IV midazolam, on Days 1, 6 and 17, to determine midazolam and 1-hydroxymidazolam plasma concentrations. 11 blood samples were collected at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 and 24 hours after the administration of oral midazolam, on Days 2, 7 and 18, to determine midazolam and 1-hydroxymidazolam plasma concentrations.'}, {'measure': 'AUC0-t for Dabigatran (Total and Free), Following Single Doses of the Parent Drug', 'timeFrame': 'In the turn of 72 hours after administration of dabigatran on day 1,6,17', 'description': 'AUC0-t =area under the curve from time zero to last sampling time with quantifiable concentrations. AUC0-t of total dabigatran and free dabigatran following Administration of Dabigatran Etexilate Alone (Day 1) and Co-Administration of Dabigatran Etexilate and Givinostat (Day 6 - Potential Inhibitory Effect, and Day 17 - Potential Inducing Effect).\n\nFifteen (15) blood samples were collected at pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours after the administration of dabigatran etexilate, on Days 1, 6 and 17, for the determination of total and free dabigatran plasma concentrations.'}, {'measure': 'AUC0-inf of Midazolam, 1-hydroxymidazolam, Following Single Doses of Givinostat', 'timeFrame': 'In the turn of 24 hours after IV midazolam, single dose, administered at day 1,6,17 or after oral midazolam, single dose, administered at days 2, 7 and 18.', 'description': 'AUC0-inf=Total AUC extrapolated to infinity, calculated as AUC0-t + Clast/λz, where Clast is the last measurable concentration and λz is the apparent terminal elimination rate constant.\n\n13 blood samples were collected at pre-dose and at 2 minutes, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 9, 12 and 24 hours after the administration of IV midazolam, on Days 1, 6 and 17, to determine midazolam and 1-hydroxymidazolam plasma concentrations. 11 blood samples were collected at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 and 24 hours after the administration of oral midazolam, on Days 2, 7 and 18, to determine midazolam and 1-hydroxymidazolam plasma concentrations.'}, {'measure': 'AUC0-inf for Dabigatran (Total and Free), Following Single Doses of the Parent Drug', 'timeFrame': 'In the turn of 72 hours after administration of dabigatran on day 1,6,17', 'description': 'AUC0-inf = Total AUC extrapolated to infinity, calculated as AUC0-t + Clast/λz, where Clast is the last measurable concentration and λz is the apparent terminal elimination rate constant. AUC0-inf of total dabigatran and free dabigatran following Administration of Dabigatran Etexilate Alone (Day 1) and Co-Administration of Dabigatran Etexilate and Givinostat (Day 6 - Potential Inhibitory Effect, and Day 17 - Potential Inducing Effect).\n\nFifteen (15) blood samples were collected at pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours after the administration of dabigatran etexilate, on Days 1, 6 and 17, for the determination of total and free dabigatran plasma concentrations.'}, {'measure': '%AUCextrap of Midazolam, 1-hydroxymidazolam, Following Single Doses of Givinostat', 'timeFrame': 'In the turn of 24 hours after IV midazolam, single dose, administered at day 1,6,17 or after oral midazolam, single dose, administered at days 2, 7 and 18.', 'description': 'Area under the curve or AUC is a pharmacokinetic statistic used to describe the total exposure to a drug. More specifically, it is the time-averaged concentration of drug circulating in the body fluid analyzed (normally plasma, blood or serum). Standard calculation of AUC involves using non-compartmental techniques to calculate the AUC from time 0 to the last measurable concentration. This is called AUC0-t and represents the observed exposure to a drug. The total AUC or AUC0-∞ is the area under the curve from time 0 extrapolated to infinite time.\n\n%AUCextrap = Percentage of AUC0-∞ due to extrapolation from the time of the last measurable concentration (tlast) to infinity, i.e., residual area, calculated as 100 ∙(AUC0-∞ - AUC0-t) / AUC0-∞.'}, {'measure': '%AUC0extrap (%) for Dabigatran (Total and Free), Following Single Doses of the Parent Drug', 'timeFrame': 'In the turn of 72 hours after administration of dabigatran on day 1,6,17', 'description': 'Area under the curve (AUC) is a pharmacokinetic statistic used to describe the total exposure to a drug. More specifically, it is the time-averaged concentration of drug circulating in the body fluid analyzed. The total AUC (AUC0-∞) is the area under the curve from time 0 extrapolated to infinite time.\n\n* AUC0extrap = Percentage of AUC0-∞ due to extrapolation from the time of the last measurable concentration (tlast) to infinity, i.e., residual area, calculated as 100 ∙(AUC0-∞ - AUC0-t) / AUC0-∞.\n* AUC0extrap of total dabigatran and free dabigatran following Administration of Dabigatran Etexilate Alone (Day 1) and Co-Administration of Dabigatran Etexilate and Givinostat (Day 6 - Potential Inhibitory Effect, and Day 17 - Potential Inducing Effect).\n\nFifteen (15) blood samples were collected at pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours after the administration of dabigatran etexilate, on Days 1, 6 and 17, for the determination of total and free dabigatra'}, {'measure': 'λz of Midazolam, 1-hydroxymidazolam, Following Single Doses of Givinostat', 'timeFrame': 'In the turn of 24 hours after IV midazolam, single dose, administered at day 1,6,17 or after oral midazolam, single dose, administered at days 2, 7 and 18.', 'description': 'Apparent first order elimination rate constant associated with the terminal (log-linear) portion of the concentration versus time curve. The parameter is estimated by linear least square regression analysis using the last three (or more) non-zero concentrations.\n\n13 blood samples were collected at pre-dose and at 2 minutes, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 9, 12 and 24 hours after the administration of IV midazolam, on Days 1, 6 and 17, to determine midazolam and 1-hydroxymidazolam plasma concentrations. 11 blood samples were collected at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 and 24 hours after the administration of oral midazolam, on Days 2, 7 and 18, to determine midazolam and 1-hydroxymidazolam plasma concentrations.'}, {'measure': 'λz of Dabigatran (Total and Free), Following Single Doses of Givinostat', 'timeFrame': 'In the turn of 24 hours after IV midazolam, single dose, administered at day 1,6,17 or after oral midazolam, single dose, administered at days 2, 7 and 18.', 'description': 'Apparent first order elimination rate constant associated with the terminal (log-linear) portion of the concentration versus time curve. The parameter is estimated by linear least square regression analysis using the last three (or more) non-zero concentrations.\n\nFifteen (15) blood samples were collected at pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours after the administration of dabigatran etexilate, on Days 1, 6 and 17, for the determination of total and free dabigatran plasma concentrations.'}], 'secondaryOutcomes': [{'measure': 'Number of Adverse Events by Severity (Mild, Moderate, Severe)', 'timeFrame': 'Throughout the study and 10-14 days after the EoS (follow-up visit), i.e. up to date 30-34', 'description': 'An AE was considered as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily imply a causal relationship with this treatment. An AE can, therefore, be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.\n\nThe period of observation for the collection of medical occurrences extended from the time when the subject gave Informed Consent until the follow-up visit.'}, {'measure': 'Incidence of Patients With at Least One Adverse Events by Severity (Mild, Moderate, Severe)', 'timeFrame': 'During the study and 10-14 days after the EoS (follow-up visit), i.e. up to day 30-34', 'description': 'An AE was considered as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily imply a causal relationship with this treatment. An AE can, therefore, be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.\n\nThe period of observation for the collection of medical occurrences extended from the time when the subject gave Informed Consent until the follow-up visit.'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['PK', 'Pharmacokinetics', 'Givinostat', 'Midazolam', 'Dabigatran'], 'conditions': ['Drug-Drug Interaction', 'Heathy Volunteer']}, 'descriptionModule': {'briefSummary': 'Primary objective:\n\n1. To assess the potential inhibitory and inducing effect of oral givinostat on the single dose pharmacokinetics (PK) of intravenous or oral midazolam.\n2. To assess the potential inhibitory and inducing effect of oral givinostat on the single dose PK of oral dabigatran etexilate.\n\nSecondary objective:\n\nTo assess the safety and tolerability of concomitant administration of givinostat plus midazolam and dabigatran etexilate.', 'detailedDescription': 'This study was planned as a phase I, open-label, 3-part, fixed-sequence, nonrandomized study in healthy male and female subjects. The study evaluated the givinostat (ITF2357) potential drug-drug interaction (DDI) at level of CYP3A-mediated metabolism and P-glycoprotein (P-gp) transport with intravenous or oral midazolam and with oral dabigatran etexilate.\n\nMore precisely, the study aimed at assessing the potential (inhibitory or inducing) effect of givinostat on the PK of midazolam IV, on the PK of oral midazolam and on the PK of dabigatran etexilate.\n\nThe study lasted from Day 1 to Day 20. Subjects were confined from Day -1 to Day 20. On Days 6 and 17, single doses of 1 mg midazolam IV and 75 mg dabigatran etexilate, were administered 1 hour after the planned morning time of givinostat administration. On day 1, however, drugs were not administered 1h after gininostat.\n\nOn Days 7 and 18, a single oral dose of 2.5 mg midazolam oral solution was administered 1 hour after the planned morning time of givinostat administration.\n\nOn day 2, however, the drugs were not administered 1h after gininostat.\n\nFrom Day 4 to Day 18, givinostat 50 mg as oral suspension was administered twice a day, in the morning and in the evening.\n\nOn Day 19, only the morning dose was administered.\n\nThe following assessments were performed:\n\n* Blood collection for pharmacokinetic analysis on Days 1 to 4, 6 to 9 and 17 to 20.\n* Vital signs measurements (BP, PR and RR) on Days 1, 2, and 4 to 19.\n* 12-lead ECG on Days 3 to 19.\n* Blood collection for laboratory tests (hematology, biochemistry and coagulation on Days 4 and 9 and hematology on Days 6, 12, 15 and 18). Subjects were discharged from BlueClinical Phase I in the morning of Day 20 if allowed by the investigator based on their medical condition. The following procedures were performed:\n* Physical examination.\n* Collection of body weight.\n* Vital signs measurements (BP, PR, RR and body temperature).\n* 12-lead ECG.\n* Safety laboratory assessments (hematology, biochemistry, coagulation and urinalysis).\n* Serum pregnancy test for all female subjects. Subjects returned to the site 10 to 14 days after the end of study to undergo additional assessments as required per protocol.\n\nThe total duration of Part 1 for each subject was up to approximately 8 weeks from Screening to Follow-up visit, divided as follows:\n\n* Screening: up to 21 days\n* Treatment Period: Days 1 to 20\n* Safety follow-up visit: 12±2 days'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT'], 'maximumAge': '55 Years', 'minimumAge': '18 Years', 'healthyVolunteers': True, 'eligibilityCriteria': "Inclusion criteria\n\nA subject was considered eligible for the study if he/she fulfilled all the inclusion criteria:\n\n1. Subject's written informed consent obtained prior to any study-related procedure.\n2. Male or female subject, ≥18 and ≤55 years of age, at the time of signing the informed consent.\n3. Body mass index (BMI) of 18.5 to 32.0 kg/m2 inclusive, and body weight ≥55 kg and ≤100 kg for females and body weight ≥60 kg and ≤110 kg for males.\n4. Non-smoker or ex-smoker (i.e. someone who abstained from using tobaccoor nicotine-containing products for at least 3 months prior to Screening).\n5. No clinically relevant diseases.\n6. No major surgery within 4 weeks prior to dosing.\n7. No clinically relevant abnormalities on physical examination.\n8. No clinically relevant abnormalities on 12-lead ECG.\n9. No clinically relevant abnormalities on clinical laboratory tests.\n10. Negative test results for anti-Human Immunodeficiency virus 1 and 2 antibodies (anti-HIV-1Ab and anti-HIV-2Ab), Hepatitis B surface antigen (HBsAg) and anti-Hepatitis C virus antibodies (anti-HCVAb).\n11. Female subjects are eligible if they are of non-childbearing potential or agree to use a non-hormonal highly effective contraceptive method from 28 days prior to Screening until at least 90 days after the last study drug administration. Nonchildbearing potential female is defined as:\n\n 1. Menopausal, i.e. no menses for ≥ 12 months without an alternative medical cause other than menopause, and a high FSH level.\n 2. Pre-menopausal female with documented hysterectomy, bilateral salpingectomy and/or bilateral oophorectomy.\n\n A non-hormonal effective contraceptive method is defined as:\n 1. Intrauterine device.\n 2. Bilateral tubal occlusion.\n 3. Total abstinence of heterosexual intercourse, in accordance with the lifestyle of the subject.\n 4. Vasectomized partner, who has received medical assessment of the surgical success, or clinically diagnosed infertile partner.\n12. Male subjects who are sexually active with a female partner of childbearing potential (pregnant or non-pregnant) must use contraception (condom) from investigational product administration up to at least 90 days following the last study drug administration.\n13. Male subjects must ensure that his non-pregnant female partner of childbearing potential agrees to consistently and correctly use for the same period a highly effective method of contraception (see Section 8.5.3).\n14. Male subjects must be willing not to donate sperm until 90 days following the last study drug administration.\n15. Willingness and capability to comply with the requirements of the study and ability to understand the study procedures and the risks involved.\n\nExclusion Criteria\n\nA subject was excluded from the study if he/she fulfilled any of the exclusion criteria:\n\nAt Screening\n\n1. Previous use of givinostat.\n2. History of anaphylaxis reaction or clinically significant drug hypersensitivity reaction (e.g., angioedema, Stevens-Johnson syndrome, acute generalized exanthematous pustulosis, drug-induced hypersensitivity syndrome, druginduced neutropenia).\n3. Known history of hypersensitivity and/or allergic reactions to givinostat, histone deacetylases (HDAC) inhibitors or to any excipient in the formulation.\n4. History of sorbitol intolerance, sorbitol malabsorption or fructose intolerance.\n5. Any medical condition (e.g. gastrointestinal, renal or hepatic, including peptic ulcer, inflammatory bowel disease or pancreatitis) or surgical condition (e.g. cholecystectomy, gastrectomy) that may affect drug pharmacokinetics (absorption, distribution, metabolism or excretion) or subject safety.\n6. Systolic blood pressure lower than 90 or over 140 mmHg, diastolic blood pressure lower than 60 or over 90 mmHg, or pulse rate lower than 50 or over 100 bpm.\n7. QTcF ˃450 msec.\n8. Subjects with history of cardiac arrhythmias (documented), family history of sudden cardiac death or history of additional risk factors for torsades-depointes (e.g. heart failure, hypokalemia, long QT syndrome).\n9. Having an estimated glomerular filtration (eGFR) \\< 90 mL/min, based on creatinine clearance calculation by the Cockcroft-Gault formula and normalized to an average surface area of 1.73 m2.\n10. Any of the following abnormal laboratory test values:\n\n 1. Platelet count below the lower limit of the normal range (LLN)\n 2. Total white blood cells count below the LLN\n 3. Hemoglobin below the LLN\n 4. Triglycerides above the upper limit of normal range (ULN)\n 5. Potassium or magnesium below the LLN\n11. Positive urine alcohol, drugs-of-abuse or cotinine screen tests.\n12. Positive serum pregnancy test.\n13. If woman, she is breast-feeding.\n14. History of alcohol abuse within 1 year prior to screening or regular use of alcohol within 6 months prior to the screening visit (i.e. more than 14 units of alcohol per week for males or more than 7 units for females).\n15. History of drug abuse within 1 year prior to screening or use of soft drugs (such as marijuana) within 3 months prior to the screening visit or hard drugs \\[such as cocaine, phencyclidine (PCP), crack, opioid derivatives including heroin, and amphetamine derivatives\\] within 1 year prior to screening.\n16. Participation in any clinical trial within the previous 2 months.\n17. Participation in more than 2 clinical trials within the previous 12 months.\n18. Blood donation or significant blood loss (≥ 450 mL) due to any reason or had plasmapheresis within the previous 2 months.\n19. Veins unsuitable for intravenous puncture on either arm.\n20. Difficulty in swallowing capsules, tablets or suspensions.\n21. Any reason which, in the opinion of the Investigator, would prevent the subject from participating in the study.\n\n Exclusion Criteria:\n\n At Admission to Treatment Period\n22. Any clinically relevant abnormalities on clinical laboratory tests.\n23. Positive urine alcohol, drugs-of-abuse or cotinine screen tests.\n24. Positive urine pregnancy test.\n25. Positive or inconclusive SARS-CoV-2 test prior to admission.\n26. Use of prescription or non-prescription medicinal products within the previous 28 days or within 5-half-lives of the medicinal product, whichever is longer.\n27. Any reason which, in the opinion of the Investigator, would prevent the subject from participating in the study.\n\n For Part 1 subjects:\n\n At Screening\n28. Known history of hypersensitivity and/or allergic reactions to midazolam, other benzodiazepines, dabigatran etexilate or to any excipient of the formulations.\n29. Clinically relevant history of impaired respiratory function, obstructive sleep apnea, myasthenia gravis, respiratory arrest and/or cardiac arrest.\n30. History of glaucoma.\n31. Presence of respiratory failure.\n32. Presence of active clinically significant bleeding.\n33. Lesion or condition considered to pose a significant risk factor for major bleeding including, but not limited to: current or recent gastrointestinal ulceration, malignant neoplasms, recent brain or spinal injury, recent brain, spinal or ophthalmic surgery, recent intracranial hemorrhage, known or suspected esophageal varices, arteriovenous malformations, vascular aneurysms or major intraspinal or intracerebral vascular abnormalities.\n34. Presence of a medical condition requiring anticoagulant treatment.\n\n At Admission to Treatment Period\n35. Treatment with anticoagulants within 28 days or 5 drug half-lives, whichever was longer, before admission."}, 'identificationModule': {'nctId': 'NCT05492318', 'briefTitle': 'Perpetrator DDI Potential of Givinostat as Inhibitor and Inducer of CYP3A and P-gp Activity', 'organization': {'class': 'INDUSTRY', 'fullName': 'Italfarmaco'}, 'officialTitle': 'Open-label, Single-center Study in Healthy Subjects to Investigate the Effect of Oral Givinostat on Pharmacokinetics (PK) of Intravenous and Oral Midazolam and Oral Dabigatran Etexilate (PART 1)', 'orgStudyIdInfo': {'id': 'ITF/2357/55 - PART 1'}, 'secondaryIdInfos': [{'id': '2021-005756-11', 'type': 'EUDRACT_NUMBER'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Givinostat alone or combo with Midazolam IV and with oral Dabigatran, or combo with oral Midazolam', 'description': 'On Days 1, 6 and 17, single doses of midazolam 1 mg IV and dabigatran etexilate 75 mg were administered 1 hour after the planned (as per Day 4) morning time of givinostat administration. On Days 2, 7 and 18, a single oral dose of midazolam 2.5 mg oral solution was administered 1 hour after the planned (as per Day 4) morning time of givinostat administration. From Day 4 to Day 18, givinostat 50 mg as oral suspension was administered twice a day, in the morning and in the evening. On Day 19, only the morning dose was administered.', 'interventionNames': ['Drug: Givinostat 10 mg/mL', 'Drug: Midazolam 1mg/ml IV', 'Drug: Midazolam 2.5 mg oromucosal solution', 'Drug: Dabigatran etexilate 75 mg oral hard capsules']}], 'interventions': [{'name': 'Givinostat 10 mg/mL', 'type': 'DRUG', 'otherNames': ['ITF2357'], 'description': '10 mg/mL oral suspension. Givinostat 10 mg/ml oral suspension was administered once, in the morning, in Days 1, 2, 6, 7, 17 and 18), and twice a day (50 mg as oral suspension), in the morning and in the evening, from the Day 4 to Day 18. On Day 19, only the morning dose was administered.', 'armGroupLabels': ['Givinostat alone or combo with Midazolam IV and with oral Dabigatran, or combo with oral Midazolam']}, {'name': 'Midazolam 1mg/ml IV', 'type': 'DRUG', 'otherNames': ['Aurobindo®'], 'description': 'Midazolam 1 mg/ml, solution for intravenous administration. Midazolam 1mg/ml IV, single dose, was administered on Days 1, 6 and 17, 1 hour after the planned morning time of givinostat administration. Midazolam IV were administered with the subjects in a semi-recumbent position. Subjects remained semirecumbent until at least 3 hours post-dose.', 'armGroupLabels': ['Givinostat alone or combo with Midazolam IV and with oral Dabigatran, or combo with oral Midazolam']}, {'name': 'Midazolam 2.5 mg oromucosal solution', 'type': 'DRUG', 'otherNames': ['Buccolam®'], 'description': 'Dose: 2.5 mg oromucosal solution. Midazolam 2.5 mg single oral solution was administered on Days 2, 7 and 18, 1 hour after the planned morning time of givinostat administration.\n\nOral midazolam (and dabigatran etexilate) was administered following an overnight fasting of at least 8 hours and subjects remained fasted until at least 3 hours post-dose.\n\nOral midazolam (and dabigatran etexilate) was administered with 150 mL of water. Except for water given with the investigational products, no fluids were allowed from 1 hour before midazolam and dabigatran dosing until 2 hours postdose. Water was provided ad libitum at all other times. Midazolam (and dabigatran etexilate) were administered with the subjects in a semi-recumbent position. Subjects remained semirecumbent until at least 3 hours post-dose.', 'armGroupLabels': ['Givinostat alone or combo with Midazolam IV and with oral Dabigatran, or combo with oral Midazolam']}, {'name': 'Dabigatran etexilate 75 mg oral hard capsules', 'type': 'DRUG', 'otherNames': ['Pradaxa'], 'description': 'Dose: 75 mg; Dosage form: hard capsules On Days 1, 6 and 17, dabigatran etexilate 75 mg was administered (with midazolam 1mg IV) 1 hour after the planned morning time of givinostat administration.\n\nDabigatran etexilate (and midazolam) was administered following an overnight fasting of at least 8 hours and subjects remained fasted until at least 3 hours post-dose Oral dabigatran etexilate (and oral midazolam) was administered with 150 mL of water. Except for water given with the investigational products, no fluids were allowed from 1 hour before dabigatran (and midazolam) dosing until 2 hours postdose. Water was provided ad libitum at all other times. Dabigatran etexilate (and Midazolam) was administered with the subjects in a semi-recumbent position. Subjects remained semirecumbent until at least 3 hours post-dose.', 'armGroupLabels': ['Givinostat alone or combo with Midazolam IV and with oral Dabigatran, or combo with oral Midazolam']}]}, 'contactsLocationsModule': {'locations': [{'zip': '153 4250-449', 'city': 'Porto', 'country': 'Portugal', 'facility': 'Hospital da Prelada, 3rd Floor & East Wing 4th Floor Rua Sarmento de Beires', 'geoPoint': {'lat': 41.1485, 'lon': -8.61097}}], 'overallOfficials': [{'name': 'Marlene Fonseca, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Blueclinical, Ltd.'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Italfarmaco', 'class': 'INDUSTRY'}, 'responsibleParty': {'type': 'SPONSOR'}}}}