Ignite Creation Date:
2025-12-25 @ 3:46 AM
Ignite Modification Date:
2026-02-28 @ 11:20 AM
Study NCT ID:
NCT01523002
Status:
COMPLETED
Last Update Posted:
2023-12-14
First Post:
2012-01-27
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Drug Interaction Study of Pyronaridine-artesunate & Metoprolol, & Redosing Study of Pyronaridine-artesunate
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D008288', 'term': 'Malaria'}], 'ancestors': [{'id': 'D011528', 'term': 'Protozoan Infections'}, {'id': 'D010272', 'term': 'Parasitic Diseases'}, {'id': 'D007239', 'term': 'Infections'}, {'id': 'D000096724', 'term': 'Mosquito-Borne Diseases'}, {'id': 'D000079426', 'term': 'Vector Borne Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D008790', 'term': 'Metoprolol'}, {'id': 'C000712628', 'term': 'pyronaridine tetraphosphate, artesunate drug combination'}], 'ancestors': [{'id': 'D050198', 'term': 'Phenoxypropanolamines'}, {'id': 'D011412', 'term': 'Propanolamines'}, {'id': 'D000605', 'term': 'Amino Alcohols'}, {'id': 'D000438', 'term': 'Alcohols'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D020005', 'term': 'Propanols'}, {'id': 'D000588', 'term': 'Amines'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'duparcs@mmv.org', 'phone': '+41 22 555 0300', 'title': 'Stephan Duparc, MD, Chief Medical Officer', 'organization': 'Medicines for Malaria Venture (MMV)'}, 'certainAgreement': {'piSponsorEmployee': False, 'restrictiveAgreement': False}}, 'adverseEventsModule': {'timeFrame': 'Arm A: 140 days + follow up if necessary Arm B: 103 days + follow up if necessary', 'description': 'An adverse event is defined as any unfavourable and unintended sign, symptom, syndrome, or illness that developed or worsened during the period of observation in the clinical study.\n\nClinically relevant abnormal results of diagnostic procedures including abnormal laboratory findings which are considered by the Investigator to be detrimental should be recorded as adverse events whether or not they have a causal relationship with the study drug.', 'eventGroups': [{'id': 'EG000', 'title': 'Arm A: Metoprolol DDI and Pyronaridine-artesunate 90-day Redosing', 'description': 'Subjects will take 1 day of metoprolol followed by a 7 day wash out period; then 2 days of pyronaridine-artesunate followed by 1 day of pyronaridine-artesunate + metoprolol and then a 87 day follow-up period. Subjects will then receive pyronaridine-artesunate once daily for three days followed by a 40 day follow-up period and a study completion evaluation.', 'otherNumAtRisk': 26, 'deathsNumAtRisk': 26, 'otherNumAffected': 25, 'seriousNumAtRisk': 26, 'deathsNumAffected': 0, 'seriousNumAffected': 0}, {'id': 'EG001', 'title': 'Arm B: Pyronaridine-artesunate 60-day Redosing', 'description': 'Subjects will take pyronaridine-artesunate once daily for 3 days, followed by a 57 day follow-up period. Subjects will then take pyronaridine-artesunate once daily for 3 days followed by a 40 day follow-up period.', 'otherNumAtRisk': 30, 'deathsNumAtRisk': 30, 'otherNumAffected': 29, 'seriousNumAtRisk': 30, 'deathsNumAffected': 0, 'seriousNumAffected': 2}], 'otherEvents': [{'term': 'Diarrhoea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 66, 'numAffected': 20}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 58, 'numAffected': 18}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedRA'}, {'term': 'Nausea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 18, 'numAffected': 12}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 13, 'numAffected': 11}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedRA'}, {'term': 'Vomiting', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 5, 'numAffected': 5}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 12, 'numAffected': 9}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedRA'}, {'term': 'Abdominal pain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 10, 'numAffected': 6}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 10, 'numAffected': 6}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedRA'}, {'term': 'Abdominal pain discomfort', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 5, 'numAffected': 3}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 3, 'numAffected': 3}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedRA'}, {'term': 'Abdominal pain upper', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 5, 'numAffected': 4}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedRA'}, {'term': 'Flatulence', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 3, 'numAffected': 3}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 3, 'numAffected': 3}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedRA'}, {'term': 'Abdominal distension', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 2, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedRA'}, {'term': 'Constipation', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedRA'}, {'term': 'Alanine aminotransferase increased', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 17, 'numAffected': 13}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 22, 'numAffected': 16}], 'organSystem': 'Investigations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedRA'}, {'term': 'Aspartate aminotransferase increased', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 9, 'numAffected': 8}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 20, 'numAffected': 17}], 'organSystem': 'Investigations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedRA'}, {'term': 'Gamma-glutamyltransferase increased', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 7, 'numAffected': 5}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 17, 'numAffected': 14}], 'organSystem': 'Investigations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedRA'}, {'term': 'Neutrophil count decreased', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 5, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 7, 'numAffected': 3}], 'organSystem': 'Investigations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedRA'}, {'term': 'Blood alkaline phosphatase increased', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 3, 'numAffected': 3}], 'organSystem': 'Investigations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedRA'}, {'term': 'Blood bilirubin increased', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 3, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Investigations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedRA'}, {'term': 'Prothrombin time prolonged', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Investigations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedRA'}, {'term': 'White blood cell count decreased', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Investigations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedRA'}, {'term': 'Platelet count increased', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Investigations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedRA'}, {'term': 'Headache', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 33, 'numAffected': 15}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 24, 'numAffected': 16}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedRA'}, {'term': 'Dizziness', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 11, 'numAffected': 9}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 7, 'numAffected': 6}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedRA'}, {'term': 'Dizziness postural', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedRA'}, {'term': 'Paraesthesia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedRA'}, {'term': 'Tremor', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedRA'}, {'term': 'Fatigue', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 13, 'numAffected': 10}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 6, 'numAffected': 5}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedRA'}, {'term': 'Chills', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 2, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedRA'}, {'term': 'Malaise', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedRA'}, {'term': 'Pyrexia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedRA'}, {'term': 'Chest discomfort', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedRA'}, {'term': 'Feeling hot', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedRA'}, {'term': 'Inflammation', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedRA'}, {'term': 'Injection site pain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedRA'}, {'term': 'Vessel puncture site', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedRA'}, {'term': 'Swelling', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedRA'}, {'term': 'Back pain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 5, 'numAffected': 4}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 8, 'numAffected': 7}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedRA'}, {'term': 'Pain in extremity', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 6, 'numAffected': 6}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedRA'}, {'term': 'Arthralgia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedRA'}, {'term': 'Myalgia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedRA'}, {'term': 'Intervertebral disc', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedRA'}, {'term': 'Nasopharngitis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 3, 'numAffected': 3}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 6, 'numAffected': 6}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedRA'}, {'term': 'Rhinitis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedRA'}, {'term': 'Herpes simplex', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedRA'}, {'term': 'Cough', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 4, 'numAffected': 4}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedRA'}, {'term': 'Epistaxis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedRA'}, {'term': 'Oropharyngeal pain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedRA'}, {'term': 'Hyponatraemia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 3, 'numAffected': 3}], 'organSystem': 'Metabolism and nutrition disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedRA'}, {'term': 'Decreased appetite', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'Metabolism and nutrition disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedRA'}, {'term': 'Proteinuria', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 5, 'numAffected': 5}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 3, 'numAffected': 3}], 'organSystem': 'Renal and urinary disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedRA'}, {'term': 'Pruritus', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 2, 'numAffected': 1}], 'organSystem': 'Skin and subcutaneous tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedRA'}, {'term': 'Rash', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 2, 'numAffected': 1}], 'organSystem': 'Skin and subcutaneous tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedRA'}, {'term': 'Dry skin', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Skin and subcutaneous tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedRA'}, {'term': 'Rash papular', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Skin and subcutaneous tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedRA'}, {'term': 'Scratch', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Injury, poisoning and procedural complications', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedRA'}, {'term': 'Thermal burn', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Injury, poisoning and procedural complications', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedRA'}, {'term': 'Tooth fracture', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Injury, poisoning and procedural complications', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedRA'}, {'term': 'Hot flush', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Vascular disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedRA'}, {'term': 'Surgery', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Surgical and medical procedures', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedRA'}, {'term': 'Tooth repair', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Surgical and medical procedures', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedRA'}, {'term': 'Eye irritation', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Eye disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedRA'}, {'term': 'Insomnia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Psychiatric disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedRA'}, {'term': 'Metrorrhagia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Reproductive system and breast disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedRA'}], 'seriousEvents': [{'term': 'Exanthema (rash)', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 3, 'numAffected': 1}], 'organSystem': 'Skin and subcutaneous tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedRA'}, {'term': 'Discus hernia (intervertebral disc protrusion)', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 3, 'numAffected': 1}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedRA'}], 'frequencyThreshold': '0'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Arm A Pharmacokinetic Parameters of Metoprolol & α-hydroxymetoprolol: Area Under Curve (AUC)0-t, AUC0-∞', 'denoms': [{'units': 'Participants', 'counts': [{'value': '26', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Arm A: Metoprolol DDI and Pyronaridine-artesunate 90-day Redosing', 'description': 'Subjects will take 1 day of metoprolol followed by a 7 day wash out period; then 2 days of pyronaridine-artesunate followed by 1 day of pyronaridine-artesunate + metoprolol and then a 87 day follow-up period. Subjects will then receive pyronaridine-artesunate once daily for 3 days followed by a 40 day follow-up period.'}], 'classes': [{'title': 'Period 1 AUC0-t Metoprolol', 'denoms': [{'units': 'Participants', 'counts': [{'value': '26', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '685', 'spread': '91', 'groupId': 'OG000'}]}]}, {'title': 'Period 1 AUC0-∞ Metoprolol', 'denoms': [{'units': 'Participants', 'counts': [{'value': '26', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '746', 'spread': '89', 'groupId': 'OG000'}]}]}, {'title': 'Period 2 AUC0-t Metoprolol', 'denoms': [{'units': 'Participants', 'counts': [{'value': '22', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '895', 'spread': '77.0', 'groupId': 'OG000'}]}]}, {'title': 'Period 2 AUC0-∞ Metoprolol', 'denoms': [{'units': 'Participants', 'counts': [{'value': '22', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '958', 'spread': '77.3', 'groupId': 'OG000'}]}]}, {'title': 'Period 1 AUC0-t α-hydroxymetoprolol', 'denoms': [{'units': 'Participants', 'counts': [{'value': '26', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '707', 'spread': '51.6', 'groupId': 'OG000'}]}]}, {'title': 'Period 1 AUC0-∞ α-hydroxymetoprolol', 'denoms': [{'units': 'Participants', 'counts': [{'value': '26', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '804', 'spread': '41.9', 'groupId': 'OG000'}]}]}, {'title': 'Period 2 AUC0-t α-hydroxymetoprolol', 'denoms': [{'units': 'Participants', 'counts': [{'value': '22', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '601', 'spread': '72.2', 'groupId': 'OG000'}]}]}, {'title': 'Period 2 AUC0-∞ α-hydroxymetoprolol', 'denoms': [{'units': 'Participants', 'counts': [{'value': '22', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '739', 'spread': '49.5', 'groupId': 'OG000'}]}]}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': 'Plasma samples taken predose and following metoprolol dosing at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 and 24 hours postdose on Days 1 & 10', 'description': 'AUC0-t \\& AUC0-∞ of Metoprolol \\& α-hydroxymetoprolol for Period 1 (metoprolol alone) \\& Period 2 (pyronaridine-artesunate with metoprolol)\n\nAbbreviations: AUC = area under the concentration-time curve; AUC0-t = AUC from Hour 0 to the last quantifiable concentration time (LQCT), where LQCT is the time at which the last sample with a quantifiable concentration was drawn; AUC0-∞ = AUC from Hour 0 to infinity', 'unitOfMeasure': 'ng.h/ml', 'dispersionType': 'Geometric Coefficient of Variation', 'reportingStatus': 'POSTED', 'populationDescription': '26 participants analyzed for Period 1, 22 participants analyzed for Period 2 (22 participants reached D10 for data collection)'}, {'type': 'PRIMARY', 'title': 'Arm A Pharmacokinetics Parameters of Metoprolol & α-hydroxymetoprolol: Tmax', 'denoms': [{'units': 'Participants', 'counts': [{'value': '26', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Arm A: Metoprolol DDI and Pyronaridine-artesunate 90-day Redosing', 'description': 'Subjects will take 1 day of metoprolol followed by a 7 day wash out period; then 2 days of pyronaridine-artesunate followed by 1 day of pyronaridine-artesunate + metoprolol and then a 87 day follow-up period. Subjects will then receive pyronaridine-artesunate once daily for 3 days followed by a 40 day follow-up period.'}], 'classes': [{'title': 'Period 1 tmax Metoprolol', 'denoms': [{'units': 'Participants', 'counts': [{'value': '26', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '1.5', 'groupId': 'OG000', 'lowerLimit': '0.75', 'upperLimit': '3.00'}]}]}, {'title': 'Period 2 tmax Metoprolol', 'denoms': [{'units': 'Participants', 'counts': [{'value': '22', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '1.00', 'groupId': 'OG000', 'lowerLimit': '0.75', 'upperLimit': '2.02'}]}]}, {'title': 'Period 1 tmax α-hydroxymetoprolol', 'denoms': [{'units': 'Participants', 'counts': [{'value': '26', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '1.5', 'groupId': 'OG000', 'lowerLimit': '0.75', 'upperLimit': '8.00'}]}]}, {'title': 'Period 2 tmax α-hydroxymetoprolol', 'denoms': [{'units': 'Participants', 'counts': [{'value': '22', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '1.5', 'groupId': 'OG000', 'lowerLimit': '0.42', 'upperLimit': '6.00'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': 'Plasma samples taken predose and following metoprolol dosing at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 and 24 hours postdose on Days 1 & 10', 'description': 'tmax of Metoprolol \\& α-hydroxymetoprolol for Period 1 (metoprolol alone) \\& Period 2 (pyronaridine-artesunate with metoprolol)\n\nAbbreviations: tmax = time to maximum observed concentration.', 'unitOfMeasure': 'hours', 'dispersionType': 'Full Range', 'reportingStatus': 'POSTED', 'populationDescription': '26 participants analyzed for Period 1, 22 participants analyzed for Period 2 (22 participants reached D10 for data collection)'}, {'type': 'PRIMARY', 'title': 'Arm A Pharmacokinetics Parameters of Metoprolol & α-hydroxymetoprolol: t1/2', 'denoms': [{'units': 'Participants', 'counts': [{'value': '26', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Arm A: Metoprolol DDI and Pyronaridine-artesunate 90-day Redosing', 'description': 'Subjects will take 1 day of metoprolol followed by a 7 day wash out period; then 2 days of pyronaridine-artesunate followed by 1 day of pyronaridine-artesunate + metoprolol and then a 87 day follow-up period. Subjects will then receive pyronaridine-artesunate once daily for 3 days followed by a 40 day follow-up period.'}], 'classes': [{'title': 'Period 1 t1/2 Metoprolol', 'denoms': [{'units': 'Participants', 'counts': [{'value': '26', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '3.39', 'spread': '24.78', 'groupId': 'OG000'}]}]}, {'title': 'Period 2 t1/2 Metoprolol', 'denoms': [{'units': 'Participants', 'counts': [{'value': '22', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '3.28', 'spread': '30.3', 'groupId': 'OG000'}]}]}, {'title': 'Period 1 t1/2 α-hydroxymetoprolol', 'denoms': [{'units': 'Participants', 'counts': [{'value': '26', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '7.34', 'spread': '30.8', 'groupId': 'OG000'}]}]}, {'title': 'Period 2 t1/2 α-hydroxymetoprolol', 'denoms': [{'units': 'Participants', 'counts': [{'value': '22', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '7.55', 'spread': '29.3', 'groupId': 'OG000'}]}]}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': 'Plasma samples taken predose and following metoprolol dosing at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 and 24 hours postdose on Days 1 & 10', 'description': 't1/2 of Metoprolol \\& α-hydroxymetoprolol for Period 1 (metoprolol alone) \\& Period 2 (pyronaridine-artesunate with metoprolol)\n\nAbbreviations: t1/2 = apparent terminal phase half-life', 'unitOfMeasure': 'hours', 'dispersionType': 'Geometric Coefficient of Variation', 'reportingStatus': 'POSTED', 'populationDescription': '26 participants analyzed for Period 1, 22 participants analyzed for Period 2 (22 participants reached D10 for data collection)'}, {'type': 'PRIMARY', 'title': 'Arm A Pharmacokinetics Parameters of Metoprolol & α-hydroxymetoprolol: Cmax', 'denoms': [{'units': 'Participants', 'counts': [{'value': '26', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Arm A: Metoprolol DDI and Pyronaridine-artesunate 90-day Redosing', 'description': 'Subjects will take 1 day of metoprolol followed by a 7 day wash out period; then 2 days of pyronaridine-artesunate followed by 1 day of pyronaridine-artesunate + metoprolol and then a 87 day follow-up period. Subjects will then receive pyronaridine-artesunate once daily for 3 days followed by a 40 day follow-up period.'}], 'classes': [{'title': 'Period 1 Cmax Metoprolol', 'denoms': [{'units': 'Participants', 'counts': [{'value': '26', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '152.7', 'spread': '77.1', 'groupId': 'OG000'}]}]}, {'title': 'Period 2 Cmax Metoprolol', 'denoms': [{'units': 'Participants', 'counts': [{'value': '22', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '228.6', 'spread': '62.3', 'groupId': 'OG000'}]}]}, {'title': 'Period 1 Cmax α-hydroxymetoprolol', 'denoms': [{'units': 'Participants', 'counts': [{'value': '26', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '73.9', 'spread': '75.9', 'groupId': 'OG000'}]}]}, {'title': 'Period 2 Cmax α-hydroxymetoprolol', 'denoms': [{'units': 'Participants', 'counts': [{'value': '22', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '66.8', 'spread': '78.4', 'groupId': 'OG000'}]}]}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': 'Plasma samples taken predose and following metoprolol dosing at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 and 24 hours postdose on Days 1 & 10', 'description': 'Cmax of Metoprolol \\& α-hydroxymetoprolol for Period 1 (metoprolol alone) \\& Period 2 (pyronaridine-artesunate with metoprolol)\n\nAbbreviations: Cmax = maximum peak observed concentration', 'unitOfMeasure': 'hours', 'dispersionType': 'Geometric Coefficient of Variation', 'reportingStatus': 'POSTED', 'populationDescription': '26 participants analyzed for Period 1, 22 participants analyzed for Period 2 (22 participants reached D10 for data collection)'}, {'type': 'PRIMARY', 'title': 'World Health Organization (WHO) Treatment Emergent Adverse Events', 'denoms': [{'units': 'Participants', 'counts': [{'value': '26', 'groupId': 'OG000'}, {'value': '30', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Arm A: Metoprolol DDI and Pyronaridine-artesunate 90-day Redosing', 'description': 'Subjects will take 1 day of metoprolol followed by a 7 day wash out period; then 2 days of pyronaridine-artesunate followed by 1 day of pyronaridine-artesunate + metoprolol and then a 87 day follow-up period. Subjects will then receive pyronaridine-artesunate once daily for 3 days followed by a 40 day follow-up period.'}, {'id': 'OG001', 'title': 'Arm B: Pyronaridine-artesunate 60-day Redosing', 'description': 'Subjects will take pyronaridine-artesunate once daily for 3 days, followed by a 57 day follow-up period. Subjects will then take pyronaridine-artesunate once daily for 3 days followed by a 40 day follow-up period.'}], 'classes': [{'title': 'Grade 1 toxicity', 'categories': [{'measurements': [{'value': '25', 'groupId': 'OG000'}, {'value': '24', 'groupId': 'OG001'}]}]}, {'title': 'Grade 2 toxicity', 'categories': [{'measurements': [{'value': '12', 'groupId': 'OG000'}, {'value': '17', 'groupId': 'OG001'}]}]}, {'title': 'Grade 3 toxicity', 'categories': [{'measurements': [{'value': '2', 'groupId': 'OG000'}, {'value': '4', 'groupId': 'OG001'}]}]}, {'title': 'Grade 4 toxicity', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '2', 'groupId': 'OG001'}]}]}], 'paramType': 'NUMBER', 'timeFrame': '140 days', 'description': 'To assess the safety of redosing a 3-day regimen of pyronaridine-artesunate. Grade 1: mild adverse event Grade 2: moderate adverse event Grade 3: severe and undesirable adverse event Grade 4: life threatening adverse event Grade 5: fatal adverse event resulting in death', 'unitOfMeasure': 'participants', 'reportingStatus': 'POSTED'}, {'type': 'PRIMARY', 'title': 'Non-WHO Listed Treatment Emergent Adverse Events', 'denoms': [{'units': 'Participants', 'counts': [{'value': '26', 'groupId': 'OG000'}, {'value': '30', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Arm A: Metoprolol DDI and Pyronaridine-artesunate 90-day Redosing', 'description': 'Subjects will take 1 day of metoprolol followed by a 7 day wash out period; then 2 days of pyronaridine-artesunate followed by 1 day of pyronaridine-artesunate + metoprolol and then a 87 day follow-up period. Subjects will then receive pyronaridine-artesunate once daily for 3 days followed by a 40 day follow-up period.'}, {'id': 'OG001', 'title': 'Arm B: Pyronaridine-artesunate 60-day Redosing', 'description': 'Subjects will take pyronaridine-artesunate once daily for 3 days, followed by a 57 day follow-up period. Subjects will then take pyronaridine-artesunate once daily for 3 days followed by a 40 day follow-up period.'}], 'classes': [{'title': 'Mild', 'categories': [{'measurements': [{'value': '23', 'groupId': 'OG000'}, {'value': '21', 'groupId': 'OG001'}]}]}, {'title': 'Moderate', 'categories': [{'measurements': [{'value': '5', 'groupId': 'OG000'}, {'value': '14', 'groupId': 'OG001'}]}]}, {'title': 'Severe', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}, {'title': 'Life-threatening', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}], 'paramType': 'NUMBER', 'timeFrame': '140 days', 'description': 'To assess the safety of redosing a 3-day regimen of pyronaridine-artesunate', 'unitOfMeasure': 'participants', 'reportingStatus': 'POSTED'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Arm A: Metoprolol DDI and Pyronaridine-artesunate 90-day Redosing', 'description': 'Subjects will take 1 day of metoprolol followed by a 7 day wash out period; then 2 days of pyronaridine-artesunate followed by 1 day of pyronaridine-artesunate + metoprolol and then a 87 day follow-up period. Subjects will then receive pyronaridine-artesunate once daily for 3 days followed by a 40 day follow-up period.'}, {'id': 'FG001', 'title': 'Arm B: Pyronaridine-artesunate 60-day Redosing', 'description': 'Subjects will take pyronaridine-artesunate once daily for 3 days, followed by a 57 day follow-up period. Subjects will then take pyronaridine-artesunate once daily for 3 days followed by a 40 day follow-up period.'}], 'periods': [{'title': 'Period 1', 'milestones': [{'type': 'STARTED', 'comment': 'Arm A: metaprolol (Day 1) Arm B: pyronaridine-artesunate (Days 1, 2 \\& 3)', 'achievements': [{'groupId': 'FG000', 'numSubjects': '26'}, {'groupId': 'FG001', 'numSubjects': '30'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '24'}, {'groupId': 'FG001', 'numSubjects': '19'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '2'}, {'groupId': 'FG001', 'numSubjects': '11'}]}], 'dropWithdraws': [{'type': 'Withdrawal by Subject', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}, {'groupId': 'FG001', 'numSubjects': '3'}]}, {'type': 'Lost to Follow-up', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}, {'groupId': 'FG001', 'numSubjects': '0'}]}, {'type': 'Adverse Event', 'reasons': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '8'}]}]}, {'title': 'Period 2', 'milestones': [{'type': 'STARTED', 'comment': 'Arm A: pyronaridine-artesunate (Days 8 \\& 9); pyronaridine-artesunate and metoprolol (Day 10) Arm B: pyronaridine-artesunate (Days 61, 62 \\& 63)', 'achievements': [{'groupId': 'FG000', 'numSubjects': '24'}, {'groupId': 'FG001', 'numSubjects': '19'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '18'}, {'groupId': 'FG001', 'numSubjects': '13'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '6'}, {'groupId': 'FG001', 'numSubjects': '6'}]}], 'dropWithdraws': [{'type': 'Withdrawal by Subject', 'reasons': [{'groupId': 'FG000', 'numSubjects': '4'}, {'groupId': 'FG001', 'numSubjects': '1'}]}, {'type': 'Adverse Event', 'reasons': [{'groupId': 'FG000', 'numSubjects': '2'}, {'groupId': 'FG001', 'numSubjects': '5'}]}]}, {'title': 'Period 3', 'milestones': [{'type': 'STARTED', 'comment': 'Arm A: Pyronaridine-artesunate (Days 98, 99 \\& 100) Arm B: NA for study design', 'achievements': [{'groupId': 'FG000', 'numSubjects': '18'}, {'comment': 'Arm B did not participate in Period 3', 'groupId': 'FG001', 'numSubjects': '0'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '14'}, {'groupId': 'FG001', 'numSubjects': '0'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '4'}, {'groupId': 'FG001', 'numSubjects': '0'}]}], 'dropWithdraws': [{'type': 'Withdrawal by Subject', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}, {'groupId': 'FG001', 'numSubjects': '0'}]}, {'type': 'Adverse Event', 'reasons': [{'groupId': 'FG000', 'numSubjects': '3'}, {'groupId': 'FG001', 'numSubjects': '0'}]}]}]}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '26', 'groupId': 'BG000'}, {'value': '30', 'groupId': 'BG001'}, {'value': '56', 'groupId': 'BG002'}]}], 'groups': [{'id': 'BG000', 'title': 'Arm A: Metoprolol DDI and Pyronaridine-artesunate 90-day Re-dosing', 'description': 'Subjects will take 1 day of metoprolol followed by a 7 day wash out period; then 2 days of pyronaridine-artesunate followed by 1 day of pyronaridine-artesunate + metoprolol and then a 87 day follow-up period. Subjects will then receive pyronaridine-artesunate once daily for three days followed by a 40 day follow-up period and a study completion evaluation.\n\nMetoprolol and pyronaridine-artesunate: On Day 1, subjects will receive a single oral 100 mg dose of metoprolol tartrate. On Day 8 and Day 9, subjects will receive a once daily oral dose of pyronaridine-artesunate as follows:\n\n55 - \\< 65 kg: 3 tablets (180:60 mg pyronaridine:artesunate)\n\n≥ 65 kg: 4 tablets (180:60 mg pyronaridine:artesunate)\n\nOn Day 10, a 100 mg dose of metoprolol will be coadministered with pyronaridine-artesunate at the above dose.\n\nOn Days 98 - 100, subjects will receive pyronaridine-artesunate once daily at the same dose described above.'}, {'id': 'BG001', 'title': 'Arm B: Pyronaridine-artesunate 60-day Re-dosing', 'description': 'Subjects will take pyronaridine-artesunate once daily for 3 days, followed by a 57 day follow-up period. Subjects will then take pyronaridine-artesunate once daily for 3 days followed by a 40 day follow-up period.\n\npyronaridine:artesunate: In the first period, subjects will receive 3 days of pyronaridine-artesunate as follows: 55 - \\< 65 kg: 3 tablets (180:60 mg pyronaridine:artesunate)\n\n≥ 65 kg: 4 tablets (180:60 mg pyronaridine:artesunate) followed by a 57 day follow-up period. In the second period, subjects will receive 3 days of pyronaridine-artesunate at the dose described above.'}, {'id': 'BG002', 'title': 'Total', 'description': 'Total of all reporting groups'}], 'measures': [{'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '45', 'spread': '7.1', 'groupId': 'BG000'}, {'value': '42', 'spread': '9.4', 'groupId': 'BG001'}, {'value': '43', 'spread': '8.4', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '13', 'groupId': 'BG000'}, {'value': '14', 'groupId': 'BG001'}, {'value': '27', 'groupId': 'BG002'}]}, {'title': 'Male', 'measurements': [{'value': '13', 'groupId': 'BG000'}, {'value': '16', 'groupId': 'BG001'}, {'value': '29', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Race/Ethnicity, Customized', 'classes': [{'title': 'Caucasian', 'categories': [{'measurements': [{'value': '24', 'groupId': 'BG000'}, {'value': '30', 'groupId': 'BG001'}, {'value': '54', 'groupId': 'BG002'}]}]}, {'title': 'Black', 'categories': [{'measurements': [{'value': '1', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '1', 'groupId': 'BG002'}]}]}, {'title': 'Oriental/Asian', 'categories': [{'measurements': [{'value': '1', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '1', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Body weight', 'classes': [{'categories': [{'measurements': [{'value': '74.4', 'spread': '11.37', 'groupId': 'BG000'}, {'value': '69.8', 'spread': '10.15', 'groupId': 'BG001'}, {'value': '71.9', 'spread': '10.88', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'kg', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Height', 'classes': [{'categories': [{'measurements': [{'value': '171', 'spread': '8.2', 'groupId': 'BG000'}, {'value': '170', 'spread': '7.4', 'groupId': 'BG001'}, {'value': '171', 'spread': '7.8', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'cm', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'BMI', 'classes': [{'categories': [{'measurements': [{'value': '25.3', 'spread': '2.59', 'groupId': 'BG000'}, {'value': '24.1', 'spread': '2.67', 'groupId': 'BG001'}, {'value': '24.6', 'spread': '2.68', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'kg/m^2', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'CYP2D6 Phenotype', 'classes': [{'categories': [{'title': 'Poor metabolizer', 'measurements': [{'value': '1', 'groupId': 'BG000'}, {'value': '2', 'groupId': 'BG001'}, {'value': '3', 'groupId': 'BG002'}]}, {'title': 'Intermediate metabolizer', 'measurements': [{'value': '11', 'groupId': 'BG000'}, {'value': '13', 'groupId': 'BG001'}, {'value': '24', 'groupId': 'BG002'}]}, {'title': 'Extensive metabolizer', 'measurements': [{'value': '13', 'groupId': 'BG000'}, {'value': '14', 'groupId': 'BG001'}, {'value': '27', 'groupId': 'BG002'}]}, {'title': 'Ultra-Rapid metabolizer', 'measurements': [{'value': '1', 'groupId': 'BG000'}, {'value': '1', 'groupId': 'BG001'}, {'value': '2', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 56}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2012-01'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2023-12', 'completionDateStruct': {'date': '2012-10', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2023-12-12', 'studyFirstSubmitDate': '2012-01-27', 'resultsFirstSubmitDate': '2021-11-18', 'studyFirstSubmitQcDate': '2012-01-31', 'lastUpdatePostDateStruct': {'date': '2023-12-14', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2023-12-12', 'studyFirstPostDateStruct': {'date': '2012-02-01', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2023-12-14', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2012-07', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Arm A Pharmacokinetic Parameters of Metoprolol & α-hydroxymetoprolol: Area Under Curve (AUC)0-t, AUC0-∞', 'timeFrame': 'Plasma samples taken predose and following metoprolol dosing at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 and 24 hours postdose on Days 1 & 10', 'description': 'AUC0-t \\& AUC0-∞ of Metoprolol \\& α-hydroxymetoprolol for Period 1 (metoprolol alone) \\& Period 2 (pyronaridine-artesunate with metoprolol)\n\nAbbreviations: AUC = area under the concentration-time curve; AUC0-t = AUC from Hour 0 to the last quantifiable concentration time (LQCT), where LQCT is the time at which the last sample with a quantifiable concentration was drawn; AUC0-∞ = AUC from Hour 0 to infinity'}, {'measure': 'Arm A Pharmacokinetics Parameters of Metoprolol & α-hydroxymetoprolol: Tmax', 'timeFrame': 'Plasma samples taken predose and following metoprolol dosing at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 and 24 hours postdose on Days 1 & 10', 'description': 'tmax of Metoprolol \\& α-hydroxymetoprolol for Period 1 (metoprolol alone) \\& Period 2 (pyronaridine-artesunate with metoprolol)\n\nAbbreviations: tmax = time to maximum observed concentration.'}, {'measure': 'Arm A Pharmacokinetics Parameters of Metoprolol & α-hydroxymetoprolol: t1/2', 'timeFrame': 'Plasma samples taken predose and following metoprolol dosing at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 and 24 hours postdose on Days 1 & 10', 'description': 't1/2 of Metoprolol \\& α-hydroxymetoprolol for Period 1 (metoprolol alone) \\& Period 2 (pyronaridine-artesunate with metoprolol)\n\nAbbreviations: t1/2 = apparent terminal phase half-life'}, {'measure': 'Arm A Pharmacokinetics Parameters of Metoprolol & α-hydroxymetoprolol: Cmax', 'timeFrame': 'Plasma samples taken predose and following metoprolol dosing at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 and 24 hours postdose on Days 1 & 10', 'description': 'Cmax of Metoprolol \\& α-hydroxymetoprolol for Period 1 (metoprolol alone) \\& Period 2 (pyronaridine-artesunate with metoprolol)\n\nAbbreviations: Cmax = maximum peak observed concentration'}, {'measure': 'World Health Organization (WHO) Treatment Emergent Adverse Events', 'timeFrame': '140 days', 'description': 'To assess the safety of redosing a 3-day regimen of pyronaridine-artesunate. Grade 1: mild adverse event Grade 2: moderate adverse event Grade 3: severe and undesirable adverse event Grade 4: life threatening adverse event Grade 5: fatal adverse event resulting in death'}, {'measure': 'Non-WHO Listed Treatment Emergent Adverse Events', 'timeFrame': '140 days', 'description': 'To assess the safety of redosing a 3-day regimen of pyronaridine-artesunate'}]}, 'oversightModule': {'oversightHasDmc': True}, 'conditionsModule': {'keywords': ['pyronaridine artesunate (Pyramax)', 'artemisinin based combination therapy (ACT)', 'metoprolol', 'drug-drug interaction study', 'redosing study'], 'conditions': ['Malaria']}, 'descriptionModule': {'briefSummary': 'The primary objective of the drug-drug interaction study is to evaluate any drug interaction between the CYP2D6 substrate metoprolol and pyronaridine-artesunate in healthy volunteers.\n\nThe primary objective of the pyronaridine-artesunate redosing study is to determine the safety of redosing a 3-day regimen of pyronaridine-artesunate following 60 or 90 days in healthy volunteers.', 'detailedDescription': 'This was a phase I, open-label, randomised, 2-arm parallel group study in healthy subjects. The study population will include 44 healthy subjects (22 per treatment arm), comprising male and female adults (18-55 years) of any ethnic origin.\n\nSubjects will be randomised to either Arm A or Arm B. Arm A will evaluate pyronaridine-artesunate interference on metoprolol pharmacokinetics (PK) and the effect of a 90-day (±7 days) redosing interval on the safety profile of pyronaridine-artesunate. Arm B will evaluate the effect of a 60-day (±7 days) redosing interval on the safety profile of pyronaridine-artesunate.\n\nScreening will be performed in the 14-day period prior to the first dose. In Arm A, each subject will partake in 3 inpatients periods between: Days -1 to 2, Days 7 to 11, and Days 97 to 101, with dosing on Days 1, 8 to 10, and 98 to 100. In Arm B, each subject will partake in 2 inpatient periods: Days -1 to 4 and Days 60 to 64, with dosing on Days 1 to 3 and 61 to 63. Subjects will be considered to have completed the study at Day 140 (Arm A) or at Day 103 (Arm B).\n\nAny adverse event ongoing at the time of study completion will be followed until resolution unless no further change is expected according to the investigator.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT'], 'maximumAge': '55 Years', 'minimumAge': '18 Years', 'healthyVolunteers': True, 'eligibilityCriteria': "Inclusion Criteria:\n\n1. Male or female subjects between the ages of 18 and 55 years with a body weight between 50 and 90 kg and a body mass index calculated using Quetelet's Index - weight (kg)/height2 (m2) between 18.5-30.0\n2. Signed and dated a written informed consent form before undergoing any study related activities\n3. Medically normal subjects with no significant abnormal findings at the screening physical examination as evaluated by the investigator\n4. Strictly normal values of alanine aminotransferase, aspartate aminotransferase, and total bilirubin and normal or abnormal and clinically insignificant results of the other blood and urine laboratory parameters at screening.\n5. Female subjects of non-childbearing potential (i.e. physiologically incapable of becoming pregnant, including any female who was post-menopausal (i.e. one year without menses) or who has undergone sterilization (via hysterectomy or bilateral tubal ligation)\n6. Female subjects of childbearing potential with a negative urine pregnancy test at screening confirmed at Day -1 by a serum pregnancy test and who agreed to one of the following methods:\n\n * Double barrier method of contraception for 2 weeks before first study drug administration and throughout the entire study follow up period\n * Partner(s) who had undergone vasectomy and has been negative for sperm for at least 6 months\n7. The ability to understand the requirements of the study and willingness to comply with all study procedures\n\nExclusion Criteria:\n\n1. Known history or evidence of clinically significant disorders such as cardiovascular (including arrhythmia, acute corrected QT interval greater or equal to 450 milliseconds), respiratory (including active tuberculosis), hepatic, renal, gastrointestinal, immunological (including active HIV-AIDS), neurological (including auditory), endocrine, infectious, malignancy, psychiatric or other abnormality (including head trauma)\n2. Known history of hypersensitivity, allergic or adverse reactions to pyronaridine or artesunate or other artemisinins or metoprolol.\n3. Other contraindications to pyronaridine use\n4. Other contraindications to metoprolol use including second or third degree atrioventricular block, heart rate below 50 beats per minute, uncompensated heart failure or need for treatment with inotropic agents, clinically apparent hypotension, sinus bradycardia or sick sinus syndrome, peripheral arterial disease, pheochromocytoma, asthma, chronic obstructive pulmonary disease, depression and any other condition with in the opinion of the Investigator may be worsened by administration of metoprolol.\n5. Known active Hepatitis A IgM (HAV-IgM), Hepatitis B surface antigen (HBsAg) or Hepatitis C antibody (HCV Ab)\n6. Seropositive HIV antibody\n7. Previous participation in any clinical study with pyronaridine:artesunate (Pyramax)\n8. Presence or recent history (last two years) of tobacco abuse (≥10 cigarettes/day)\n9. Known or suspected alcohol abuse or illicit drug use 10 years before the study start or positive findings on urine drug screen\n10. Intake of alcoholic beverages within 72 hours before study drug administration or caffeine-containing food or beverages, such as coffee, tea, chocolate, or cola, 48 hours before study drug administration\n11. Gilbert's disease\n12. Administration of any systemic medication or herbal product within 14 days before the first dose of study drug. If the investigator considers that the specific product would not interfere with the safety of the subject or the objectives of the study, topical treatments as well as vitamins and mineral supplements not containing other substances are allowed until 4 days before each dose. Ibuprofen at doses of at most 1200 mg per day for no more than 3 consecutive days or 6 non-consecutive days is allowed until 24h before the first dose of study drug.\n13. Plasma donation 3 months before the study start\n14. Blood donation of 500 mL or more 3 months before the study start\n15. Participation in any clinical study in last 3 months"}, 'identificationModule': {'nctId': 'NCT01523002', 'briefTitle': 'Drug Interaction Study of Pyronaridine-artesunate & Metoprolol, & Redosing Study of Pyronaridine-artesunate', 'organization': {'class': 'OTHER', 'fullName': 'Medicines for Malaria Venture'}, 'officialTitle': 'Open-label, Drug Interaction Study of Pyronaridine-artesunate and Metoprolol in Healthy Volunteers and Pyronaridine-artesunate Redosing Study in Healthy Volunteers', 'orgStudyIdInfo': {'id': 'SP-C-014-11'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'ACTIVE_COMPARATOR', 'label': 'Arm A: metoprolol and pyronaridine-artesunate 90-day redosing', 'description': 'Subjects will take 1 day of metoprolol followed by a 7 day wash out period, then 2 days of pyronaridine-artesunate followed by 1 day of pyronaridine-artesunate + metoprolol, followed by a 87 day follow-up period. Subjects will then receive pyronaridine-artesunate once daily for 3 days followed by a 40 day follow-up period.', 'interventionNames': ['Drug: Metoprolol and pyronaridine-artesunate']}, {'type': 'ACTIVE_COMPARATOR', 'label': 'Arm B: pyronaridine-artesunate 60-day redosing', 'description': 'Subjects will take pyronaridine-artesunate once daily for 3 days, followed by a 57 day follow-up period. Subjects will then take pyronaridine-artesunate once daily for 3 days followed by a 40 day follow-up period.', 'interventionNames': ['Drug: pyronaridine-artesunate']}], 'interventions': [{'name': 'Metoprolol and pyronaridine-artesunate', 'type': 'DRUG', 'description': 'On Day 1, subjects will receive a single oral 100 mg dose of metoprolol tartrate. On Day 8 and Day 9, subjects will receive a once daily oral dose of pyronaridine-artesunate as follows:\n\n55 - \\< 65 kg: 3 tablets (180:60 mg pyronaridine:artesunate)\n\n≥ 65 kg: 4 tablets (180:60 mg pyronaridine:artesunate)\n\nOn Day 10, a 100 mg dose of metoprolol will be coadministered with pyronaridine-artesunate at the above dose.\n\nOn Days 98 - 100, subjects will receive pyronaridine-artesunate once daily at the same dose described above. Followed by a 40 day follow-up period.', 'armGroupLabels': ['Arm A: metoprolol and pyronaridine-artesunate 90-day redosing']}, {'name': 'pyronaridine-artesunate', 'type': 'DRUG', 'otherNames': ['Pyramax'], 'description': 'On Days 1 to 3, subjects will receive 3 days of pyronaridine-artesunate as follows:\n\n55 - \\< 65 kg: 3 tablets (180:60 mg pyronaridine:artesunate)\n\n≥ 65 kg: 4 tablets (180:60 mg pyronaridine:artesunate)\n\nOn Days 61 to 63, subjects will be redosed with a 3 day course of pyronaridine-artesunate at the above dose.\n\nFollowed by a 40 day follow-up period.', 'armGroupLabels': ['Arm B: pyronaridine-artesunate 60-day redosing']}]}, 'contactsLocationsModule': {'locations': [{'zip': '4123', 'city': 'Allschwil', 'state': 'Basel', 'country': 'Switzerland', 'facility': 'Covance Clinical Research Unit AG', 'geoPoint': {'lat': 47.55074, 'lon': 7.53599}}], 'overallOfficials': [{'name': 'Rolf Pokorny, MD, MSc', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Covance Research Unit AG'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Medicines for Malaria Venture', 'class': 'OTHER'}, 'collaborators': [{'name': 'Shin Poong Pharmaceuticals', 'class': 'INDUSTRY'}], 'responsibleParty': {'type': 'SPONSOR'}}}}