Ignite Creation Date:
2025-12-25 @ 4:27 AM
Ignite Modification Date:
2025-12-26 @ 3:31 AM
Study NCT ID:
NCT03548220
Status:
COMPLETED
Last Update Posted:
2022-05-24
First Post:
2018-05-24
Is NOT Gene Therapy:
False
Has Adverse Events:
True
Brief Title:
A Study to Evaluate Efficacy and Safety of AG-348 in Not Regularly Transfused Adult Participants With Pyruvate Kinase Deficiency (PKD)
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24', 'removedCountries': ['Poland', 'Portugal'], 'submissionTracking': {'firstMcpInfo': {'postDateStruct': {'date': '2021-11-08', 'type': 'ACTUAL'}}}}, 'conditionBrowseModule': {'meshes': [{'id': 'C564858', 'term': 'Pyruvate Kinase Deficiency of Red Cells'}, {'id': 'D000743', 'term': 'Anemia, Hemolytic'}], 'ancestors': [{'id': 'D000740', 'term': 'Anemia'}, {'id': 'D006402', 'term': 'Hematologic Diseases'}, {'id': 'D006425', 'term': 'Hemic and Lymphatic Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C000634504', 'term': 'mitapivat'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'medinfo@agios.com', 'phone': '833-228-8474', 'title': 'Medical Affairs', 'organization': 'Agios Pharmaceuticals, Inc.'}, 'certainAgreement': {'otherDetails': 'The information obtained from the clinical study will be used towards the development of AG-348 and may be disclosed to regulatory authority(ies), other Investigators, corporate partners, or consultants as required', 'restrictionType': 'OTHER', 'piSponsorEmployee': False, 'restrictiveAgreement': True}}, 'adverseEventsModule': {'timeFrame': 'From time of signing of informed consent form to end of study, including follow-up (up to Day 197)', 'description': 'The placebo arm includes AEs that occurred in participants who received at least 1 dose of AG-348 matching placebo during the study. As pre-specified in SAP, AEs that occurred in AG-348 arms for participants who received AG-348 treatment during the study are reported based on the fixed dose treatment received. The safety analysis set included all participants who received at least 1 dose of study treatment.', 'eventGroups': [{'id': 'EG000', 'title': 'Placebo Comparator: Placebo', 'description': 'Participants received a matching placebo to AG-348 tablets, for a period of 12 weeks as an optimized dose. This was followed by matching placebo further, for a period of 12 weeks as a fixed-dose.', 'otherNumAtRisk': 39, 'deathsNumAtRisk': 39, 'otherNumAffected': 35, 'seriousNumAtRisk': 39, 'deathsNumAffected': 0, 'seriousNumAffected': 2}, {'id': 'EG001', 'title': 'Experimental: AG-348, 5 mg', 'description': 'Participants received AG-348 tablets, 5 mg BID, administered orally, for 4 weeks as a starting dose, followed by two potential sequential dose level increases to 20 mg and 50 mg BID at Weeks 4 and 8 respectively as determined by the investigator based on safety and efficacy. The optimized dose for each participant was determined as 5 mg BID at Week 12, and participants then received that optimized dose for a period of 12 weeks as a fixed dose.', 'otherNumAtRisk': 2, 'deathsNumAtRisk': 2, 'otherNumAffected': 1, 'seriousNumAtRisk': 2, 'deathsNumAffected': 0, 'seriousNumAffected': 0}, {'id': 'EG002', 'title': 'Experimental: AG-348, 20 mg', 'description': 'Participants received AG-348 tablets, 5 mg BID, administered orally, for 4 weeks as a starting dose, followed by two potential sequential dose level increases to 20 mg and 50 mg BID at Weeks 4 and 8 respectively as determined by the investigator based on safety and efficacy. The optimized dose for each participant was determined as 20 mg BID at Week 12, and participants then received that optimized dose for a period of 12 weeks as a fixed dose.', 'otherNumAtRisk': 3, 'deathsNumAtRisk': 3, 'otherNumAffected': 3, 'seriousNumAtRisk': 3, 'deathsNumAffected': 0, 'seriousNumAffected': 1}, {'id': 'EG003', 'title': 'Experimental: AG-348, 50 mg', 'description': 'Participants received AG-348 tablets, 5 mg BID, administered orally, for 4 weeks as a starting dose, followed by two potential sequential dose level increases to 20 mg and 50 mg BID at Weeks 4 and 8 respectively as determined by the investigator based on safety and efficacy. The optimized dose for each participant was determined as 50 mg BID at Week 12, and participants then received that optimized dose for a period of 12 weeks as a fixed dose.', 'otherNumAtRisk': 35, 'deathsNumAtRisk': 35, 'otherNumAffected': 31, 'seriousNumAtRisk': 35, 'deathsNumAffected': 0, 'seriousNumAffected': 3}], 'otherEvents': [{'term': 'Nausea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 39, 'numAffected': 9}, {'groupId': 'EG001', 'numAtRisk': 2, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 3, 'numAffected': 2}, {'groupId': 'EG003', 'numAtRisk': 35, 'numAffected': 5}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Diarrhoea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 39, 'numAffected': 7}, {'groupId': 'EG001', 'numAtRisk': 2, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 3, 'numAffected': 2}, {'groupId': 'EG003', 'numAtRisk': 35, 'numAffected': 2}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Abdominal pain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 39, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 2, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 3, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 35, 'numAffected': 4}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Abdominal distension', 'stats': [{'groupId': 'EG000', 'numAtRisk': 39, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 2, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 3, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 35, 'numAffected': 2}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Constipation', 'stats': [{'groupId': 'EG000', 'numAtRisk': 39, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 2, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 3, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 35, 'numAffected': 2}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Dyspepsia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 39, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 2, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 3, 'numAffected': 1}, {'groupId': 'EG003', 'numAtRisk': 35, 'numAffected': 0}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Abdominal pain upper', 'stats': [{'groupId': 'EG000', 'numAtRisk': 39, 'numAffected': 3}, {'groupId': 'EG001', 'numAtRisk': 2, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 3, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 35, 'numAffected': 0}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Nasopharyngitis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 39, 'numAffected': 6}, {'groupId': 'EG001', 'numAtRisk': 2, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 3, 'numAffected': 2}, {'groupId': 'EG003', 'numAtRisk': 35, 'numAffected': 3}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Gastroenteritis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 39, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 2, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 3, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 35, 'numAffected': 2}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Urinary tract infection', 'stats': [{'groupId': 'EG000', 'numAtRisk': 39, 'numAffected': 3}, {'groupId': 'EG001', 'numAtRisk': 2, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 3, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 35, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Upper respiratory tract infection', 'stats': [{'groupId': 'EG000', 'numAtRisk': 39, 'numAffected': 4}, {'groupId': 'EG001', 'numAtRisk': 2, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 3, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 35, 'numAffected': 0}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Oral herpes', 'stats': [{'groupId': 'EG000', 'numAtRisk': 39, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 2, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 3, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 35, 'numAffected': 0}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Back pain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 39, 'numAffected': 3}, {'groupId': 'EG001', 'numAtRisk': 2, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 3, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 35, 'numAffected': 5}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Arthralgia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 39, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 2, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 3, 'numAffected': 2}, {'groupId': 'EG003', 'numAtRisk': 35, 'numAffected': 2}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Pain in extremity', 'stats': [{'groupId': 'EG000', 'numAtRisk': 39, 'numAffected': 3}, {'groupId': 'EG001', 'numAtRisk': 2, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 3, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 35, 'numAffected': 2}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Neck pain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 39, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 2, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 3, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 35, 'numAffected': 0}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Dyspnoea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 39, 'numAffected': 4}, {'groupId': 'EG001', 'numAtRisk': 2, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 3, 'numAffected': 1}, {'groupId': 'EG003', 'numAtRisk': 35, 'numAffected': 2}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Cough', 'stats': [{'groupId': 'EG000', 'numAtRisk': 39, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 2, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 3, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 35, 'numAffected': 3}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Oropharyngeal pain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 39, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 2, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 3, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 35, 'numAffected': 3}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Nasal congestion', 'stats': [{'groupId': 'EG000', 'numAtRisk': 39, 'numAffected': 3}, {'groupId': 'EG001', 'numAtRisk': 2, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 3, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 35, 'numAffected': 2}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Rhinitis allergic', 'stats': [{'groupId': 'EG000', 'numAtRisk': 39, 'numAffected': 3}, {'groupId': 'EG001', 'numAtRisk': 2, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 3, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 35, 'numAffected': 1}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Epistaxis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 39, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 2, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 3, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 35, 'numAffected': 1}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Fatigue', 'stats': [{'groupId': 'EG000', 'numAtRisk': 39, 'numAffected': 4}, {'groupId': 'EG001', 'numAtRisk': 2, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 3, 'numAffected': 1}, {'groupId': 'EG003', 'numAtRisk': 35, 'numAffected': 4}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Influenza like illness', 'stats': [{'groupId': 'EG000', 'numAtRisk': 39, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 2, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 3, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 35, 'numAffected': 2}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Pyrexia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 39, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 2, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 3, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 35, 'numAffected': 0}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Headache', 'stats': [{'groupId': 'EG000', 'numAtRisk': 39, 'numAffected': 13}, {'groupId': 'EG001', 'numAtRisk': 2, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 3, 'numAffected': 1}, {'groupId': 'EG003', 'numAtRisk': 35, 'numAffected': 5}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Dizziness', 'stats': [{'groupId': 'EG000', 'numAtRisk': 39, 'numAffected': 3}, {'groupId': 'EG001', 'numAtRisk': 2, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 3, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 35, 'numAffected': 4}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Presyncope', 'stats': [{'groupId': 'EG000', 'numAtRisk': 39, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 2, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 3, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 35, 'numAffected': 2}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Paraesthesia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 39, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 2, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 3, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 35, 'numAffected': 2}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Middle insomnia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 39, 'numAffected': 3}, {'groupId': 'EG001', 'numAtRisk': 2, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 3, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 35, 'numAffected': 3}], 'organSystem': 'Psychiatric disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Insomnia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 39, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 2, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 3, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 35, 'numAffected': 2}], 'organSystem': 'Psychiatric disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Initial insomnia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 39, 'numAffected': 4}, {'groupId': 'EG001', 'numAtRisk': 2, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 3, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 35, 'numAffected': 1}], 'organSystem': 'Psychiatric disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Stress', 'stats': [{'groupId': 'EG000', 'numAtRisk': 39, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 2, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 3, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 35, 'numAffected': 0}], 'organSystem': 'Psychiatric disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Dry skin', 'stats': [{'groupId': 'EG000', 'numAtRisk': 39, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 2, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 3, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 35, 'numAffected': 2}], 'organSystem': 'Skin and subcutaneous tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Rash', 'stats': [{'groupId': 'EG000', 'numAtRisk': 39, 'numAffected': 3}, {'groupId': 'EG001', 'numAtRisk': 2, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 3, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 35, 'numAffected': 0}], 'organSystem': 'Skin and subcutaneous tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Dermatitis acneiform', 'stats': [{'groupId': 'EG000', 'numAtRisk': 39, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 2, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 3, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 35, 'numAffected': 0}], 'organSystem': 'Skin and subcutaneous tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Breast discomfort', 'stats': [{'groupId': 'EG000', 'numAtRisk': 39, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 2, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 3, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 35, 'numAffected': 2}], 'organSystem': 'Reproductive system and breast disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Dysmenorrhoea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 39, 'numAffected': 3}, {'groupId': 'EG001', 'numAtRisk': 2, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 3, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 35, 'numAffected': 1}], 'organSystem': 'Reproductive system and breast disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Hot flush', 'stats': [{'groupId': 'EG000', 'numAtRisk': 39, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 2, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 3, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 35, 'numAffected': 3}], 'organSystem': 'Vascular disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Hypertension', 'stats': [{'groupId': 'EG000', 'numAtRisk': 39, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 2, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 3, 'numAffected': 1}, {'groupId': 'EG003', 'numAtRisk': 35, 'numAffected': 1}], 'organSystem': 'Vascular disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Contusion', 'stats': [{'groupId': 'EG000', 'numAtRisk': 39, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 2, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 3, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 35, 'numAffected': 2}], 'organSystem': 'Injury, poisoning and procedural complications', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Hypertriglyceridaemia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 39, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 2, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 3, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 35, 'numAffected': 3}], 'organSystem': 'Metabolism and nutrition disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Anaemia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 39, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 2, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 3, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 35, 'numAffected': 0}], 'organSystem': 'Blood and lymphatic system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Alanine aminotransferase increased', 'stats': [{'groupId': 'EG000', 'numAtRisk': 39, 'numAffected': 6}, {'groupId': 'EG001', 'numAtRisk': 2, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 3, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 35, 'numAffected': 1}], 'organSystem': 'Investigations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Aspartate aminotransferase increased', 'stats': [{'groupId': 'EG000', 'numAtRisk': 39, 'numAffected': 3}, {'groupId': 'EG001', 'numAtRisk': 2, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 3, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 35, 'numAffected': 1}], 'organSystem': 'Investigations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}], 'seriousEvents': [{'term': 'Gastroenteritis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 39, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 2, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 3, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 35, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Metapneumovirus infection', 'stats': [{'groupId': 'EG000', 'numAtRisk': 39, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 2, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 3, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 35, 'numAffected': 0}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Atrial fibrillation', 'stats': [{'groupId': 'EG000', 'numAtRisk': 39, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 2, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 3, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 35, 'numAffected': 1}], 'organSystem': 'Cardiac disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Rib fracture', 'stats': [{'groupId': 'EG000', 'numAtRisk': 39, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 2, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 3, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 35, 'numAffected': 1}], 'organSystem': 'Injury, poisoning and procedural complications', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Musculoskeletal pain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 39, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 2, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 3, 'numAffected': 1}, {'groupId': 'EG003', 'numAtRisk': 35, 'numAffected': 0}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Obstructive pancreatitis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 39, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 2, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 3, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 35, 'numAffected': 0}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}], 'frequencyThreshold': '5'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Percentage of Participants Achieving a Hemoglobin (Hb) Response (HR)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '40', 'groupId': 'OG000'}, {'value': '40', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Placebo Comparator: Placebo', 'description': 'Participants received matching placebo to AG-348 tablets, for a period of 12 weeks as an optimized dose. This was followed by matching placebo further, for a period of 12 weeks as a fixed-dose.'}, {'id': 'OG001', 'title': 'Experimental: AG-348', 'description': 'Participants received AG-348 tablets, 5 mg for 4 weeks followed by the respective optimized dose of 5 mg or 20 mg or 50 mg BID as determined by the investigator, administered orally, up to Weeks 8 and 12 respectively, as an optimized dose and continued to receive the same dose for a period of 12 weeks as a fixed-dose.'}], 'classes': [{'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '40.0', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '<0.0001', 'groupIds': ['OG000', 'OG001'], 'pValueComment': '2-sided p-value', 'statisticalMethod': 'Exact Cochran-Mantel-Haenszel', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'NUMBER', 'timeFrame': 'Baseline, Weeks 16, 20, 24', 'description': 'Hemoglobin response (HR) is defined as a ≥1.5 g/dL (0.93 mmol/L) increase in Hb concentration from baseline that is sustained at 2 or more scheduled assessments at Weeks 16, 20, and 24. The baseline Hb concentration is the average of all available Hb concentrations for a participant during the Screening Period up to the first dose of study treatment. As pre-specified in the protocol, the data for this outcome measure is summarized between the active arm vs the placebo arm (AG-348 5 mg, 20 mg and 50 mg arms are analyzed and reported together in comparison to Placebo).', 'unitOfMeasure': 'percentage of participants', 'reportingStatus': 'POSTED', 'populationDescription': 'Full analysis set included all participants who were randomized.'}, {'type': 'SECONDARY', 'title': 'Average Change From Baseline in Hb Concentration at Weeks 16, 20 and 24', 'denoms': [{'units': 'Participants', 'counts': [{'value': '40', 'groupId': 'OG000'}, {'value': '40', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Placebo Comparator: Placebo', 'description': 'Participants received matching placebo to AG-348 tablets, for a period of 12 weeks as an optimized dose. This was followed by matching placebo further, for a period of 12 weeks as a fixed dose.'}, {'id': 'OG001', 'title': 'Experimental: AG-348', 'description': 'Participants received AG-348 tablets, 5 mg for 4 weeks followed by the respective optimized dose of 5 mg or 20 mg or 50 mg BID as determined by the investigator, administered orally, up to Weeks 8 and 12 respectively, as an optimized dose and continued to receive the same dose for a period of 12 weeks as a fixed-dose.'}], 'classes': [{'categories': [{'measurements': [{'value': '-1.48', 'spread': '2.082', 'groupId': 'OG000'}, {'value': '16.73', 'spread': '2.075', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '<0.0001', 'groupIds': ['OG000', 'OG001'], 'paramType': 'LS Mean Difference', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '18.21', 'ciLowerLimit': '12.41', 'ciUpperLimit': '24.01', 'estimateComment': 'Standard error = 2.913', 'statisticalMethod': 'Mixed-effect Model Repeated Measure', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'Baseline, Weeks 16, 20, 24', 'description': 'This is the change in Hb concentration at Weeks 16, 20 and 24 compared to baseline. Data presented represents the value of the change from baseline averaged over Weeks 16, 20 and 24. Baseline was defined as the average of all screening assessments within 45 (42+3) days before randomization for participants randomized and not dosed or before start of study treatment for participants randomized and dosed. As pre-specified in the protocol, the data for this outcome measure is summarized between the active arm vs the placebo arm (AG-348 5 mg, 20 mg and 50 mg arms are analyzed and reported together in comparison to Placebo).', 'unitOfMeasure': 'grams per liter (g/L)', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Full analysis set included all participants who were randomized.'}, {'type': 'SECONDARY', 'title': 'Maximum Change From Baseline in Hb Concentration', 'denoms': [{'units': 'Participants', 'counts': [{'value': '39', 'groupId': 'OG000'}, {'value': '39', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Placebo Comparator: Placebo', 'description': 'Participants received matching placebo to AG-348 tablets, for a period of 12 weeks as an optimized dose. This was followed by matching placebo further, for a period of 12 weeks as a fixed dose.'}, {'id': 'OG001', 'title': 'Experimental: AG-348', 'description': 'Participants received AG-348 tablets, 5 mg for 4 weeks followed by the respective optimized dose of 5 mg or 20 mg or 50 mg BID as determined by the investigator, administered orally, up to Weeks 8 and 12 respectively, as an optimized dose and continued to receive the same dose for a period of 12 weeks as a fixed-dose.'}], 'classes': [{'categories': [{'measurements': [{'value': '4.76', 'spread': '4.217', 'groupId': 'OG000'}, {'value': '23.94', 'spread': '21.367', 'groupId': 'OG001'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'Baseline, up to Week 24', 'description': 'This is the maximum change from baseline in Hb concentration up to Week 24. As pre-specified in the protocol, the data for this outcome measure is summarized between the active arm vs the placebo arm (AG-348 5 mg, 20 mg and 50 mg arms are analyzed and reported together in comparison to Placebo).', 'unitOfMeasure': 'g/L', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'Full analysis set included all participants who were randomized. Overall number of participants analyzed is the number of participants evaluated for the outcome measure.'}, {'type': 'SECONDARY', 'title': 'Time to Achieve an Increase in Hb Concentration of 1.5 g/dL or More', 'denoms': [{'units': 'Participants', 'counts': [{'value': '0', 'groupId': 'OG000'}, {'value': '17', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Placebo Comparator: Placebo', 'description': 'Participants received matching placebo to AG-348 tablets, for a period of 12 weeks as an optimized dose. This was followed by matching placebo further, for a period of 12 weeks as a fixed dose.'}, {'id': 'OG001', 'title': 'Experimental: AG-348', 'description': 'Participants received AG-348 tablets, 5 mg for 4 weeks followed by the respective optimized dose of 5 mg or 20 mg or 50 mg BID as determined by the investigator, administered orally, up to Weeks 8 and 12 respectively, as an optimized dose and continued to receive the same dose for a period of 12 weeks as a fixed-dose.'}], 'classes': [{'categories': [{'measurements': [{'value': '7.66', 'spread': '4.050', 'groupId': 'OG001'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'Baseline, up to Week 24', 'description': 'This is the time taken to first achieve an increase of hemoglobin concentration of 1.5 g/dL or more from baseline. As pre-specified in the protocol, the data for this outcome measure is summarized between the active arm vs the placebo arm (AG-348 5 mg, 20 mg and 50 mg arms are analyzed and reported together in comparison to Placebo).', 'unitOfMeasure': 'weeks', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'Full analysis set included all participants who were randomized. Overall number of participants analyzed is the number of participants evaluated for the outcome measure.'}, {'type': 'SECONDARY', 'title': 'Average Change From Baseline in Indirect Bilirubin at Weeks 16, 20 and 24', 'denoms': [{'units': 'Participants', 'counts': [{'value': '39', 'groupId': 'OG000'}, {'value': '37', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Placebo Comparator: Placebo', 'description': 'Participants received matching placebo to AG-348 tablets, for a period of 12 weeks as an optimized dose. This was followed by matching placebo further, for a period of 12 weeks as a fixed dose.'}, {'id': 'OG001', 'title': 'Experimental: AG-348', 'description': 'Participants received AG-348 tablets, 5 mg for 4 weeks followed by the respective optimized dose of 5 mg or 20 mg or 50 mg BID as determined by the investigator, administered orally, up to Weeks 8 and 12 respectively, as an optimized dose and continued to receive the same dose for a period of 12 weeks as a fixed-dose.'}], 'classes': [{'categories': [{'measurements': [{'value': '5.10', 'spread': '4.061', 'groupId': 'OG000'}, {'value': '-21.16', 'spread': '4.228', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '<0.0001', 'groupIds': ['OG000', 'OG001'], 'paramType': 'LS Mean Difference', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-26.26', 'ciLowerLimit': '-37.82', 'ciUpperLimit': '-14.70', 'estimateComment': 'Standard error = 5.788', 'statisticalMethod': 'Mixed-effect Model Repeated Measure', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'Baseline, Weeks 16, 20, 24', 'description': 'The change from baseline in indirect bilirubin levels was summarized. Indirect bilirubin is a marker for hemolysis. Data presented represents the value of the change from baseline averaged over Weeks 16, 20 and 24. Baseline was defined as the average of all screening assessments within 45 (42+3) days before randomization for participants randomized and not dosed or before the start of study treatment for participants randomized and dosed. As pre-specified in the protocol, the data for this outcome measure is summarized between the active arm vs the placebo arm (AG-348 5 mg, 20 mg and 50 mg arms are analyzed and reported together in comparison to Placebo).', 'unitOfMeasure': 'micromoles per liter (μmol/L)', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Full analysis set included all participants who were randomized. Overall number of participants analyzed is the number of participants evaluated for the outcome measure.'}, {'type': 'SECONDARY', 'title': 'Average Change From Baseline in Lactic Acid Dehydrogenase (LDH) at Weeks 16, 20 and 24', 'denoms': [{'units': 'Participants', 'counts': [{'value': '40', 'groupId': 'OG000'}, {'value': '39', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Placebo Comparator: Placebo', 'description': 'Participants received matching placebo to AG-348 tablets, for a period of 12 weeks as an optimized dose. This was followed by matching placebo further, for a period of 12 weeks as a fixed dose.'}, {'id': 'OG001', 'title': 'Experimental: AG-348', 'description': 'Participants received AG-348 tablets, 5 mg for 4 weeks followed by the respective optimized dose of 5 mg or 20 mg or 50 mg BID as determined by the investigator, administered orally, up to Weeks 8 and 12 respectively, as an optimized dose and continued to receive the same dose for a period of 12 weeks as a fixed-dose.'}], 'classes': [{'categories': [{'measurements': [{'value': '-21.18', 'spread': '16.040', 'groupId': 'OG000'}, {'value': '-91.99', 'spread': '16.222', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.0027', 'groupIds': ['OG000', 'OG001'], 'paramType': 'LS Mean Difference', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-70.81', 'ciLowerLimit': '-115.88', 'ciUpperLimit': '-25.74', 'estimateComment': 'Standard error = 22.488', 'statisticalMethod': 'Mixed-effect Model Repeated Measure', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'Baseline, Weeks 16, 20, 24', 'description': 'The change from baseline in LDH levels was summarized. LDH is a marker for hemolysis. Data presented represents the value of the change from baseline averaged over Weeks 16, 20 and 24. Baseline was defined as the average of all screening assessments within 45 (42+3) days before randomization for participants randomized and not dosed or before the start of study treatment for participants randomized and dosed. As pre-specified in the protocol, the data for this outcome measure is summarized between the active arm vs the placebo arm (AG-348 5 mg, 20 mg and 50 mg arms are analyzed and reported together in comparison to Placebo).', 'unitOfMeasure': 'units per litre (U/L)', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Full analysis set included all participants who were randomized. Overall number of participants analyzed is the number of participants evaluated for the outcome measure.'}, {'type': 'SECONDARY', 'title': 'Average Change From Baseline in Haptoglobin at Weeks 16, 20 and 24', 'denoms': [{'units': 'Participants', 'counts': [{'value': '40', 'groupId': 'OG000'}, {'value': '40', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Placebo Comparator: Placebo', 'description': 'Participants received matching placebo to AG-348 tablets, for a period of 12 weeks as an optimized dose. This was followed by matching placebo further, for a period of 12 weeks as a fixed dose.'}, {'id': 'OG001', 'title': 'Experimental: AG-348', 'description': 'Participants received AG-348 tablets, 5 mg for 4 weeks followed by the respective optimized dose of 5 mg or 20 mg or 50 mg BID as determined by the investigator, administered orally, up to Weeks 8 and 12 respectively, as an optimized dose and continued to receive the same dose for a period of 12 weeks as a fixed-dose.'}], 'classes': [{'categories': [{'measurements': [{'value': '0.012', 'spread': '0.0412', 'groupId': 'OG000'}, {'value': '0.169', 'spread': '0.0408', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.0079', 'groupIds': ['OG000', 'OG001'], 'paramType': 'LS Mean Difference', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '0.158', 'ciLowerLimit': '0.043', 'ciUpperLimit': '0.273', 'estimateComment': 'Standard error = 0.0578', 'statisticalMethod': 'Mixed-effect Model Repeated Measure', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'Baseline, Weeks 16, 20, 24', 'description': 'The change from baseline in haptoglobin levels was summarized. Haptoglobin levels are markers for hemolysis. Data presented represents the value of the change from baseline averaged over Weeks 16, 20 and 24. Baseline was defined as the average of all screening assessments within 45 (42+3) days before randomization for participants randomized and not dosed or before the start of study treatment for participants randomized and dosed. As pre-specified in the protocol, the data for this outcome measure is summarized between the active arm vs the placebo arm (AG-348 5 mg, 20 mg and 50 mg arms are analyzed and reported together in comparison to Placebo).', 'unitOfMeasure': 'g/L', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Full analysis set included all participants who were randomized.'}, {'type': 'SECONDARY', 'title': 'Average Change From Baseline in Reticulocyte Percentages at Weeks 16, 20 and 24', 'denoms': [{'units': 'Participants', 'counts': [{'value': '40', 'groupId': 'OG000'}, {'value': '40', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Placebo Comparator: Placebo', 'description': 'Participants received matching placebo to AG-348 tablets, for a period of 12 weeks as an optimized dose. This was followed by matching placebo further, for a period of 12 weeks as a fixed dose.'}, {'id': 'OG001', 'title': 'Experimental: AG-348', 'description': 'Participants received AG-348 tablets, 5 mg for 4 weeks followed by the respective optimized dose of 5 mg or 20 mg or 50 mg BID as determined by the investigator, administered orally, up to Weeks 8 and 12 respectively, as an optimized dose and continued to receive the same dose for a period of 12 weeks as a fixed-dose.'}], 'classes': [{'categories': [{'measurements': [{'value': '0.0038', 'spread': '0.01390', 'groupId': 'OG000'}, {'value': '-0.0973', 'spread': '0.01401', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '<0.0001', 'groupIds': ['OG000', 'OG001'], 'paramType': 'LS Mean Difference', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-0.1011', 'ciLowerLimit': '-0.1391', 'ciUpperLimit': '-0.0632', 'estimateComment': 'Standard error = 0.01904', 'statisticalMethod': 'Mixed-effect Model Repeated Measure', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'Baseline, Weeks 16, 20, 24', 'description': 'The change from baseline in reticulocyte percentage was summarized. Reticulocyte levels are markers for hematopoietic activity. Data presented represents the value of the change from baseline averaged over Weeks 16, 20 and 24. Baseline was defined as the average of all screening assessments within 45 (42+3) days before randomization for participants randomized and not dosed or before the start of study treatment for participants randomized and dosed. As pre-specified in the protocol, the data for this outcome measure is summarized between the active arm vs the placebo arm (AG-348 5 mg, 20 mg and 50 mg arms are analyzed and reported together in comparison to Placebo).', 'unitOfMeasure': 'Reticulocyte percentages', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Full analysis set included all participants who were randomized.'}, {'type': 'SECONDARY', 'title': 'Change From Baseline in Pyruvate Kinase Deficiency Diary (PKDD) Score at Week 24', 'denoms': [{'units': 'Participants', 'counts': [{'value': '36', 'groupId': 'OG000'}, {'value': '37', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Placebo Comparator: Placebo', 'description': 'Participants received matching placebo to AG-348 tablets, for a period of 12 weeks as an optimized dose. This was followed by matching placebo further, for a period of 12 weeks as a fixed dose.'}, {'id': 'OG001', 'title': 'Experimental: AG-348', 'description': 'Participants received AG-348 tablets, 5 mg for 4 weeks followed by the respective optimized dose of 5 mg or 20 mg or 50 mg BID as determined by the investigator, administered orally, up to Weeks 8 and 12 respectively, as an optimized dose and continued to receive the same dose for a period of 12 weeks as a fixed-dose.'}], 'classes': [{'categories': [{'measurements': [{'value': '-2.05', 'spread': '0.976', 'groupId': 'OG000'}, {'value': '-5.16', 'spread': '0.955', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.0247', 'groupIds': ['OG000', 'OG001'], 'paramType': 'LS Mean Difference', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-3.11', 'ciLowerLimit': '-5.80', 'ciUpperLimit': '-0.41', 'estimateComment': 'Standard error = 1.352', 'statisticalMethod': 'Mixed-effect Model Repeated Measure', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'Baseline, Week 24', 'description': 'The PKDD is a 7-item patient reported outcome (PRO) measure of the core signs and symptoms associated with PK deficiency in adults. Participants rate their experience with symptoms of PK deficiency on the present day. The symptoms include those associated with tiredness, jaundice, bone pain, shortness of breath, and energy level. The score ranges from 25 to 76, with higher scores indicating a higher disease burden. The change from baseline in PKDD weekly scores was evaluated. A negative change from baseline indicates a lower disease burden. As pre-specified in the protocol, the data for this outcome measure is summarized between the active arm vs the placebo arm (AG-348 5 mg, 20 mg and 50 mg arms are analyzed and reported together in comparison to Placebo).', 'unitOfMeasure': 'score on a scale', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Full analysis set included all participants who were randomized. Overall number of participants analyzed is the number of participants evaluated for the outcome measure.'}, {'type': 'SECONDARY', 'title': 'Change From Baseline in Pyruvate Kinase Deficiency Impact Assessment (PKDIA) Score at Week 24', 'denoms': [{'units': 'Participants', 'counts': [{'value': '39', 'groupId': 'OG000'}, {'value': '39', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Placebo Comparator: Placebo', 'description': 'Participants received matching placebo to AG-348 tablets, for a period of 12 weeks as an optimized dose. This was followed by matching placebo further, for a period of 12 weeks as a fixed dose.'}, {'id': 'OG001', 'title': 'Experimental: AG-348', 'description': 'Participants received AG-348 tablets, 5 mg for 4 weeks followed by the respective optimized dose of 5 mg or 20 mg or 50 mg BID as determined by the investigator, administered orally, up to Weeks 8 and 12 respectively, as an optimized dose and continued to receive the same dose for a period of 12 weeks as a fixed-dose.'}], 'classes': [{'categories': [{'measurements': [{'value': '-1.39', 'spread': '1.157', 'groupId': 'OG000'}, {'value': '-4.65', 'spread': '1.123', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.0421', 'groupIds': ['OG000', 'OG001'], 'paramType': 'LS Mean Difference', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-3.25', 'ciLowerLimit': '-6.39', 'ciUpperLimit': '-0.12', 'estimateComment': 'Standard error = 1.574', 'statisticalMethod': 'Mixed-effect Model Repeated Measure', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'Baseline, Week 24', 'description': 'The PKDIA is a 12-item patient reported outcome (PRO) measure of the common impacts of PK deficiency on activities of daily living. Participants rate how PK deficiency has impacted aspects of daily living in the past 7 days, including impacts on relationships; perceived appearance; work performance; and leisure, social, mental, and physical activities. The score range is 30 to 76, with higher scores indicating a higher disease burden. The change from baseline in PKDIA scores was evaluated. A negative change from baseline indicates a lower disease burden. As pre-specified in the protocol, the data for this outcome measure is summarized between the active arm vs the placebo arm (AG-348 5 mg, 20 mg and 50 mg arms are analyzed and reported together in comparison to Placebo).', 'unitOfMeasure': 'score on a scale', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Full analysis set included all participants who were randomized. Overall number of participants analyzed is the number of participants evaluated for the outcome measure.'}, {'type': 'SECONDARY', 'title': 'Percentage of Participants With Adverse Events', 'denoms': [{'units': 'Participants', 'counts': [{'value': '39', 'groupId': 'OG000'}, {'value': '2', 'groupId': 'OG001'}, {'value': '3', 'groupId': 'OG002'}, {'value': '35', 'groupId': 'OG003'}]}], 'groups': [{'id': 'OG000', 'title': 'Placebo Comparator: Placebo', 'description': 'Participants received matching placebo to AG-348 tablets, for a period of 12 weeks as an optimized dose. This was followed by matching placebo further, for a period of 12 weeks as a fixed dose.'}, {'id': 'OG001', 'title': 'Experimental: AG-348 5 mg', 'description': 'Participants received AG-348 tablets, 5 mg BID, administered orally, for 4 weeks as a starting dose, followed by two potential sequential dose level increases to 20 mg and 50 mg BID at Weeks 4 and 8 respectively as determined by the investigator based on safety and efficacy. The optimized dose for each participant was determined as 5 mg BID at Week 12, and participants then received that optimized dose for a period of 12 weeks as a fixed dose'}, {'id': 'OG002', 'title': 'Experimental: AG-348 20 mg', 'description': 'Participants received AG-348 tablets, 5 mg BID, administered orally, for 4 weeks as a starting dose, followed by two potential sequential dose level increases to 20 mg and 50 mg BID at Weeks 4 and 8 respectively as determined by the investigator based on safety and efficacy. The optimized dose for each participant was determined as 20 mg BID at Week 12, and participants then received that optimized dose for a period of 12 weeks as a fixed dose.'}, {'id': 'OG003', 'title': 'Experimental: AG-348 50 mg', 'description': 'Participants received AG-348 tablets, 5 mg BID, administered orally, for 4 weeks as a starting dose, followed by two potential sequential dose level increases to 20 mg and 50 mg BID at Weeks 4 and 8 respectively as determined by the investigator based on safety and efficacy. The optimized dose for each participant was determined as 50 mg BID at Week 12, and participants then received that optimized dose for a period of 12 weeks as a fixed dose.'}], 'classes': [{'categories': [{'measurements': [{'value': '89.7', 'groupId': 'OG000'}, {'value': '50.0', 'groupId': 'OG001'}, {'value': '100', 'groupId': 'OG002'}, {'value': '88.6', 'groupId': 'OG003'}]}]}], 'paramType': 'NUMBER', 'timeFrame': 'From signing of informed consent form to the end of study, including follow-up (up to Day 197)', 'description': 'An AE is any untoward medical occurrence in a participant or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the study 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.', 'unitOfMeasure': 'percentage of participants', 'reportingStatus': 'POSTED', 'populationDescription': 'Safety analysis set included all participants who received at least 1 dose of study treatment.'}, {'type': 'SECONDARY', 'title': 'Area Under the Curve From Time 0 to the Last Quantifiable Concentration [AUC(0-last)] for AG-348 at Week 12', 'denoms': [{'units': 'Participants', 'counts': [{'value': '2', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}, {'value': '24', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': 'AG-348, 5mg', 'description': 'Participants received 5mg AG-348 tablets BID at Week 12.'}, {'id': 'OG001', 'title': 'AG-348, 20 mg', 'description': 'Participants received 20mg AG-348 tablets BID at Week 12.'}, {'id': 'OG002', 'title': 'AG-348, 50mg', 'description': 'Participants received 50mg AG-348 tablets BID at Week 12.'}], 'classes': [{'categories': [{'measurements': [{'value': '565.9', 'spread': 'NA', 'comment': 'Data was not reported due to small size of sample.', 'groupId': 'OG000'}, {'value': '1481.2', 'spread': '26.9', 'groupId': 'OG001'}, {'value': '2973.3', 'spread': '35.6', 'groupId': 'OG002'}]}]}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': 'Pre-dose, 30 minutes and 1, 2, 4 and 8 hours post-dose on Day 85 (Week 12)', 'unitOfMeasure': 'h*ng/mL', 'dispersionType': 'Geometric Coefficient of Variation', 'reportingStatus': 'POSTED', 'populationDescription': 'Pharmacokinetic analysis population consisted of all participants who were enrolled and received a dose of study medication (mitapivat) with at least 1 non-zero pharmacokinetic plasma concentration of mitapivat at the Week 12 visit. Overall number of participants analyzed is the number of participants evaluated for the outcome measure.'}, {'type': 'SECONDARY', 'title': 'Maximum Plasma Concentration (Cmax) for AG-348', 'denoms': [{'units': 'Participants', 'counts': [{'value': '2', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}, {'value': '26', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': 'AG-348, 5mg', 'description': 'Participants received 5mg AG-348 tablets BID at Week 12.'}, {'id': 'OG001', 'title': 'AG-348, 20 mg', 'description': 'Participants received 20mg AG-348 tablets BID at Week 12.'}, {'id': 'OG002', 'title': 'AG-348, 50mg', 'description': 'Participants received 50mg AG-348 tablets BID at Week 12.'}], 'classes': [{'categories': [{'measurements': [{'value': '156.9', 'spread': 'NA', 'comment': 'Data not reported due to small size of sample.', 'groupId': 'OG000'}, {'value': '373.1', 'spread': '13.6', 'groupId': 'OG001'}, {'value': '1033', 'spread': '31.2', 'groupId': 'OG002'}]}]}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': 'Pre-dose, 30 minutes and 1, 2, 4 and 8 hours post-dose on Day 85 (Week 12)', 'unitOfMeasure': 'Nanograms per milliliter (ng/mL)', 'dispersionType': 'Geometric Coefficient of Variation', 'reportingStatus': 'POSTED', 'populationDescription': 'Pharmacokinetic analysis population consisted of all participants who were enrolled and received a dose of study medication (mitapivat) with at least 1 non-zero pharmacokinetic plasma concentration of mitapivat at the Week 12 visit. Overall number of participants analyzed is the number of participants evaluated for the outcome measure.'}, {'type': 'SECONDARY', 'title': 'Time to Cmax (Tmax) for AG-348', 'denoms': [{'units': 'Participants', 'counts': [{'value': '2', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}, {'value': '26', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': 'AG-348, 5mg', 'description': 'Participants received 5mg AG-348 tablets BID at Week 12.'}, {'id': 'OG001', 'title': 'AG-348, 20mg', 'description': 'Participants received 20mg AG-348 tablets BID at Week 12.'}, {'id': 'OG002', 'title': 'AG-348, 50mg', 'description': 'Participants received 50mg AG-348 tablets BID at Week 12.'}], 'classes': [{'categories': [{'measurements': [{'value': '0.75', 'groupId': 'OG000', 'lowerLimit': '0.50', 'upperLimit': '1.00'}, {'value': '1.02', 'groupId': 'OG001', 'lowerLimit': '0.92', 'upperLimit': '2.17'}, {'value': '0.50', 'groupId': 'OG002', 'lowerLimit': '0.42', 'upperLimit': '1.92'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': 'Pre-dose, 30 minutes and 1, 2, 4 and 8 hours post-dose on Day 85 (Week 12)', 'unitOfMeasure': 'hours (h)', 'dispersionType': 'Full Range', 'reportingStatus': 'POSTED', 'populationDescription': 'Pharmacokinetic analysis population consisted of all participants who were enrolled and received a dose of study medication (mitapivat) with at least 1 non-zero pharmacokinetic plasma concentration of mitapivat at the Week 12 visit. Overall number of participants analyzed is the number of participants evaluated for the outcome measure.'}, {'type': 'SECONDARY', 'title': 'Time to Last Measurable Concentration (Tlast) for AG-348', 'denoms': [{'units': 'Participants', 'counts': [{'value': '2', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}, {'value': '24', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': 'AG-348, 5mg', 'description': 'Participants received 5mg AG-348 tablets BID at Week 12.'}, {'id': 'OG001', 'title': 'AG-348, 20mg', 'description': 'Participants received 20mg AG-348 tablets BID at Week 12.'}, {'id': 'OG002', 'title': 'AG-346, 50mg', 'description': 'Participants received 50mg AG-348 tablets BID at Week 12.'}], 'classes': [{'categories': [{'measurements': [{'value': '7.787', 'spread': 'NA', 'comment': 'Data not reported due to small size of sample.', 'groupId': 'OG000'}, {'value': '7.809', 'spread': '4.2', 'groupId': 'OG001'}, {'value': '7.162', 'spread': '28.0', 'groupId': 'OG002'}]}]}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': 'Pre-dose, 30 minutes and 1, 2, 4 and 8 hours post-dose on Day 85 (Week 12)', 'unitOfMeasure': 'hours (h)', 'dispersionType': 'Geometric Coefficient of Variation', 'reportingStatus': 'POSTED', 'populationDescription': 'Pharmacokinetic analysis population consisted of all participants who were enrolled and received a dose of study medication (mitapivat) with at least 1 non-zero pharmacokinetic plasma concentration of mitapivat at the Week 12 visit. Overall number of participants analyzed is the number of participants evaluated for the outcome measure.'}, {'type': 'SECONDARY', 'title': 'Exposure-Response Relationship of Adverse Event (Hot Flush) and AG-348 Concentration and Relevant AG-348 Pharmacokinetic Parameters', 'denoms': [{'units': 'Participants', 'counts': [{'value': '2', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}, {'value': '150', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': 'Experimental: AG-348 5 mg', 'description': 'Participants received AG-348 tablets, 5 mg BID, administered orally, for 4 weeks as a starting dose, participants continued to receive the same dose as determined by the investigator based on safety and efficacy up to Week 12, followed by the same optimized dose of 5 mg BID, for a period of 12 weeks as a fixed-dose.'}, {'id': 'OG001', 'title': 'Experimental: AG-348 20 mg', 'description': 'Participants received AG-348 tablets, starting dose of 5 mg BID for 4 weeks, the dose was uptitrated to 20 mg BID, administered orally, up to Week 12 as an optimized dose as determined by the investigator based on safety and efficacy, followed by the same optimized dose of 20 mg BID further for a period of 12 weeks as a fixed-dose.'}, {'id': 'OG002', 'title': 'Experimental: AG-348 50 mg', 'description': 'Participants received AG-348 tablets, starting dose of 5 mg BID for 4 weeks, the dose was uptitrated to 20 mg BID, administered orally, up to Week 8 followed by dose up titration to 50 mg BID up to Week 12 as an optimized dose, followed by the same optimized dose of 50 mg BID, as determined by the investigator based on safety and efficacy, further for a period of 12 weeks as a fixed-dose.'}], 'classes': [{'categories': [{'measurements': [{'value': '3.37', 'groupId': 'OG000', 'lowerLimit': '1.22', 'upperLimit': '7.35'}, {'value': '4.03', 'groupId': 'OG001', 'lowerLimit': '1.61', 'upperLimit': '8.36'}, {'value': '5.5', 'groupId': 'OG002', 'lowerLimit': '2.48', 'upperLimit': '10.5'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'From first dose of mitapivat to the end of study, including follow-up (up to Day 197)', 'description': 'Predicted probability of experiencing all grade hot flush at the doses of 5, 20, and 50 mg mitapivat BID based on exposure-response model.', 'unitOfMeasure': 'Percent probability', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED', 'populationDescription': 'Safety Set: Participants who were administered the study drug. Participants who received mitapivat in studies: study AG348-C-003 (NCT02476916): 52 participants; study AG348-C-006 (NCT03548220): 40 participants; study AG348-C-007 (NCT03559699): 27 participants; and study AG348-C-011 (NCT03853798): 36 participants, were pooled for the analysis of this outcome measure.'}, {'type': 'OTHER_PRE_SPECIFIED', 'title': 'Percentage of Participants With Adverse Events of Special Interest (AESI)', 'timeFrame': 'Through 4 weeks after last dose (approximately Week 31)', 'description': 'An AE is any untoward medical occurrence in a participant or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the study 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. An AESI can be serious or non-serious.', 'reportingStatus': 'NOT_POSTED', 'denomUnitsSelected': 'Participants'}, {'type': 'OTHER_PRE_SPECIFIED', 'title': 'Change From Baseline in Bone Mineral Density Z-Score at Week 24', 'timeFrame': 'Baseline, Week 24', 'reportingStatus': 'NOT_POSTED', 'denomUnitsSelected': 'Participants'}, {'type': 'OTHER_PRE_SPECIFIED', 'title': 'Change From Baseline in Bone Mineral Density T-Score at Week 24', 'timeFrame': 'Baseline, Week 24', 'reportingStatus': 'NOT_POSTED', 'denomUnitsSelected': 'Participants'}, {'type': 'SECONDARY', 'title': 'Exposure-Response Relationship Between Safety Parameters (Sex Hormone in Male Subjects) and AG-348 Concentration and Relevant AG-348 Pharmacokinetic Parameters', 'denoms': [{'units': 'Participants', 'counts': [{'value': '2', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}, {'value': '63', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': 'Experimental: AG-348 5 mg', 'description': 'Participants received AG-348 tablets, 5 mg BID, administered orally, for 4 weeks as a starting dose, participants continued to receive the same dose as determined by the investigator based on safety and efficacy up to Week 12, followed by the same optimized dose of 5 mg BID, for a period of 12 weeks as a fixed-dose.'}, {'id': 'OG001', 'title': 'Experimental: AG-348 20 mg', 'description': 'Participants received AG-348 tablets, starting dose of 5 mg BID for 4 weeks, the dose was uptitrated to 20 mg BID, administered orally, up to Week 12 as an optimized dose as determined by the investigator based on safety and efficacy, followed by the same optimized dose of 20 mg BID further for a period of 12 weeks as a fixed-dose.'}, {'id': 'OG002', 'title': 'Experimental: AG-348 50 mg', 'description': 'Participants received AG-348 tablets, starting dose of 5 mg BID for 4 weeks, the dose was uptitrated to 20 mg BID, administered orally, up to Week 8 followed by dose up titration to 50 mg BID up to Week 12 as an optimized dose, followed by the same optimized dose of 50 mg BID, as determined by the investigator based on safety and efficacy, further for a period of 12 weeks as a fixed-dose.'}], 'classes': [{'title': 'Total Testosterone', 'categories': [{'measurements': [{'value': '0.877', 'groupId': 'OG000', 'lowerLimit': '0.41', 'upperLimit': '1.43'}, {'value': '3.18', 'groupId': 'OG001', 'lowerLimit': '1.49', 'upperLimit': '5.4'}, {'value': '7.59', 'groupId': 'OG002', 'lowerLimit': '3.29', 'upperLimit': '13.7'}]}]}, {'title': 'Free Testosterone', 'categories': [{'measurements': [{'value': '6.01', 'groupId': 'OG000', 'lowerLimit': '1.66', 'upperLimit': '13.2'}, {'value': '14.1', 'groupId': 'OG001', 'lowerLimit': '4', 'upperLimit': '27.5'}, {'value': '26', 'groupId': 'OG002', 'lowerLimit': '7.14', 'upperLimit': '55.1'}]}]}, {'title': 'Estrone', 'categories': [{'measurements': [{'value': '-31.5', 'groupId': 'OG000', 'lowerLimit': '-51', 'upperLimit': '-21.1'}, {'value': '-56.5', 'groupId': 'OG001', 'lowerLimit': '-67.3', 'upperLimit': '-48.4'}, {'value': '-68.2', 'groupId': 'OG002', 'lowerLimit': '-74.5', 'upperLimit': '-62.6'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'Baseline, Week 24', 'description': 'Predicted percent change from baseline at Week 24 in the sex hormone measures (total testosterone, free testosterone, and estrone) at the doses of 5, 20, and 50 mg mitapivat BID in male participants.', 'unitOfMeasure': 'Percent change', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED', 'populationDescription': 'Safety Set: Participants who were administered the study drug. Male participants who received mitapivat in studies: study AG348-C-003 (NCT02476916): 32 participants; study AG348-C-006 (NCT03548220):15 participants; study AG348-C-007 (NCT03559699): 7 participants; and study AG348-C-011 (NCT03853798): 14 participants were pooled for analysis of this outcome measure.'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Placebo Comparator: Placebo', 'description': 'Participants received a matching placebo to AG-348 tablets, for a period of 12 weeks as an optimized dose. This was followed by matching placebo further, for a period of 12 weeks as a fixed-dose.'}, {'id': 'FG001', 'title': 'Experimental: AG-348 5 mg', 'description': 'Participants received AG-348 tablets, 5 milligrams (mg) twice daily (BID), administered orally, for 4 weeks as a starting dose, followed by two potential sequential dose level increases to 20 mg and 50 mg BID at Weeks 4 and 8 respectively as determined by the investigator based on safety and efficacy. The optimized dose for each participant was determined as 5 mg BID at Week 12, and participants then received that optimized dose for a period of 12 weeks as a fixed dose.'}, {'id': 'FG002', 'title': 'Experimental: AG-348, 20 mg', 'description': 'Participants received AG-348 tablets, 5 mg BID, administered orally, for 4 weeks as a starting dose, followed by two potential sequential dose level increases to 20 mg and 50 mg BID at Weeks 4 and 8 respectively as determined by the investigator based on safety and efficacy. The optimized dose for each participant was determined as 20 mg BID at Week 12, and participants then received that optimized dose for a period of 12 weeks as a fixed dose.'}, {'id': 'FG003', 'title': 'Experimental: AG-348, 50 mg', 'description': 'Participants received AG-348 tablets, 5 mg BID, administered orally, for 4 weeks as a starting dose, followed by two potential sequential dose level increases to 20 mg and 50 mg BID at Weeks 4 and 8 respectively as determined by the investigator based on safety and efficacy. The optimized dose for each participant was determined as 50 mg BID at Week 12, and participants then received that optimized dose for a period of 12 weeks as a fixed dose.'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '40'}, {'groupId': 'FG001', 'numSubjects': '2'}, {'groupId': 'FG002', 'numSubjects': '3'}, {'groupId': 'FG003', 'numSubjects': '35'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '39'}, {'groupId': 'FG001', 'numSubjects': '2'}, {'groupId': 'FG002', 'numSubjects': '3'}, {'groupId': 'FG003', 'numSubjects': '35'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '1'}, {'groupId': 'FG001', 'numSubjects': '0'}, {'groupId': 'FG002', 'numSubjects': '0'}, {'groupId': 'FG003', 'numSubjects': '0'}]}], 'dropWithdraws': [{'type': 'Lost to Follow-up', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}, {'groupId': 'FG001', 'numSubjects': '0'}, {'groupId': 'FG002', 'numSubjects': '0'}, {'groupId': 'FG003', 'numSubjects': '0'}]}]}], 'recruitmentDetails': 'A total of 80 participants were randomized in the study, which was conducted across multiple sites in 14 countries: Brazil, Canada, Denmark, France, Germany, Italy, Japan, Republic of Korea, Netherlands, Spain, Switzerland, Turkey, United Kingdom, and United States. The study was conducted from 9 August 2018 to 9 October 2020.', 'preAssignmentDetails': 'Screening was done for a period of 42 days after the participant provided the informed consent. Investigators determined if the participants met all the inclusion criteria and none of the exclusion criteria to receive AG-348 or placebo to determine the optimized dose to be received for 12 weeks as fixed-dose.'}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '40', 'groupId': 'BG000'}, {'value': '2', 'groupId': 'BG001'}, {'value': '3', 'groupId': 'BG002'}, {'value': '35', 'groupId': 'BG003'}, {'value': '80', 'groupId': 'BG004'}]}], 'groups': [{'id': 'BG000', 'title': 'Placebo Comparator: Placebo', 'description': 'Participants received a matching placebo to AG-348 tablets, for a period of 12 weeks as an optimized dose. This was followed by matching placebo further, for a period of 12 weeks as a fixed-dose.'}, {'id': 'BG001', 'title': 'Experimental: AG-348, 5 mg', 'description': 'Participants received AG-348 tablets, 5 mg BID, administered orally, for 4 weeks as a starting dose, followed by two potential sequential dose level increases to 20 mg and 50 mg BID at Weeks 4 and 8 respectively as determined by the investigator based on safety and efficacy. The optimized dose for each participant was determined as 5 mg BID at Week 12, and participants then received that optimized dose for a period of 12 weeks as a fixed dose.'}, {'id': 'BG002', 'title': 'Experimental: AG-348, 20 mg', 'description': 'Participants received AG-348 tablets, 5 mg BID, administered orally, for 4 weeks as a starting dose, followed by two potential sequential dose level increases to 20 mg and 50 mg BID at Weeks 4 and 8 respectively as determined by the investigator based on safety and efficacy. The optimized dose for each participant was determined as 20 mg BID at Week 12, and participants then received that optimized dose for a period of 12 weeks as a fixed dose.'}, {'id': 'BG003', 'title': 'Experimental: AG-348, 50 mg', 'description': 'Participants received AG-348 tablets, 5 mg BID, administered orally, for 4 weeks as a starting dose, followed by two potential sequential dose level increases to 20 mg and 50 mg BID at Weeks 4 and 8 respectively as determined by the investigator based on safety and efficacy. The optimized dose for each participant was determined as 50 mg BID at Week 12, and participants then received that optimized dose for a period of 12 weeks as a fixed dose.'}, {'id': 'BG004', 'title': 'Total', 'description': 'Total of all reporting groups'}], 'measures': [{'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '37.2', 'spread': '15.92', 'groupId': 'BG000'}, {'value': '21.5', 'spread': '4.95', 'groupId': 'BG001'}, {'value': '48.0', 'spread': '26.21', 'groupId': 'BG002'}, {'value': '35.8', 'spread': '14.07', 'groupId': 'BG003'}, {'value': '36.6', 'spread': '15.47', 'groupId': 'BG004'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '24', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '2', 'groupId': 'BG002'}, {'value': '22', 'groupId': 'BG003'}, {'value': '48', 'groupId': 'BG004'}]}, {'title': 'Male', 'measurements': [{'value': '16', 'groupId': 'BG000'}, {'value': '2', 'groupId': 'BG001'}, {'value': '1', 'groupId': 'BG002'}, {'value': '13', 'groupId': 'BG003'}, {'value': '32', 'groupId': 'BG004'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Ethnicity (NIH/OMB)', 'classes': [{'categories': [{'title': 'Hispanic or Latino', 'measurements': [{'value': '1', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}, {'value': '2', 'groupId': 'BG003'}, {'value': '3', 'groupId': 'BG004'}]}, {'title': 'Not Hispanic or Latino', 'measurements': [{'value': '34', 'groupId': 'BG000'}, {'value': '1', 'groupId': 'BG001'}, {'value': '2', 'groupId': 'BG002'}, {'value': '25', 'groupId': 'BG003'}, {'value': '62', 'groupId': 'BG004'}]}, {'title': 'Unknown or Not Reported', 'measurements': [{'value': '5', 'groupId': 'BG000'}, {'value': '1', 'groupId': 'BG001'}, {'value': '1', 'groupId': 'BG002'}, {'value': '8', 'groupId': 'BG003'}, {'value': '15', 'groupId': 'BG004'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Race (NIH/OMB)', 'classes': [{'categories': [{'title': 'American Indian or Alaska Native', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}, {'value': '0', 'groupId': 'BG003'}, {'value': '0', 'groupId': 'BG004'}]}, {'title': 'Asian', 'measurements': [{'value': '3', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}, {'value': '5', 'groupId': 'BG003'}, {'value': '8', 'groupId': 'BG004'}]}, {'title': 'Native Hawaiian or Other Pacific Islander', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}, {'value': '1', 'groupId': 'BG003'}, {'value': '1', 'groupId': 'BG004'}]}, {'title': 'Black or African American', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}, {'value': '0', 'groupId': 'BG003'}, {'value': '0', 'groupId': 'BG004'}]}, {'title': 'White', 'measurements': [{'value': '32', 'groupId': 'BG000'}, {'value': '2', 'groupId': 'BG001'}, {'value': '3', 'groupId': 'BG002'}, {'value': '23', 'groupId': 'BG003'}, {'value': '60', 'groupId': 'BG004'}]}, {'title': 'More than one race', 'measurements': [{'value': '1', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}, {'value': '0', 'groupId': 'BG003'}, {'value': '1', 'groupId': 'BG004'}]}, {'title': 'Unknown or Not Reported', 'measurements': [{'value': '4', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}, {'value': '6', 'groupId': 'BG003'}, {'value': '10', 'groupId': 'BG004'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}], 'populationDescription': 'Full analysis set included all participants who were randomized.'}}, 'documentSection': {'largeDocumentModule': {'largeDocs': [{'date': '2019-08-14', 'size': 994645, 'label': 'Study Protocol', 'hasIcf': False, 'hasSap': False, 'filename': 'Prot_000.pdf', 'typeAbbrev': 'Prot', 'uploadDate': '2021-10-08T10:45', 'hasProtocol': True}, {'date': '2020-06-30', 'size': 775123, 'label': 'Statistical Analysis Plan', 'hasIcf': False, 'hasSap': True, 'filename': 'SAP_002.pdf', 'typeAbbrev': 'SAP', 'uploadDate': '2021-12-23T11:13', 'hasProtocol': False}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE3'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'TRIPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR']}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 80}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2018-08-09', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2022-05', 'completionDateStruct': {'date': '2020-10-09', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2022-05-20', 'studyFirstSubmitDate': '2018-05-24', 'resultsFirstSubmitDate': '2021-10-08', 'studyFirstSubmitQcDate': '2018-06-05', 'lastUpdatePostDateStruct': {'date': '2022-05-24', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2022-05-20', 'studyFirstPostDateStruct': {'date': '2018-06-07', 'type': 'ACTUAL'}, 'resultsFirstPostDateStruct': {'date': '2022-05-24', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2020-10-09', 'type': 'ACTUAL'}}, 'outcomesModule': {'otherOutcomes': [{'measure': 'Percentage of Participants With Adverse Events of Special Interest (AESI)', 'timeFrame': 'Through 4 weeks after last dose (approximately Week 31)', 'description': 'An AE is any untoward medical occurrence in a participant or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the study 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. An AESI can be serious or non-serious.'}, {'measure': 'Change From Baseline in Bone Mineral Density Z-Score at Week 24', 'timeFrame': 'Baseline, Week 24'}, {'measure': 'Change From Baseline in Bone Mineral Density T-Score at Week 24', 'timeFrame': 'Baseline, Week 24'}], 'primaryOutcomes': [{'measure': 'Percentage of Participants Achieving a Hemoglobin (Hb) Response (HR)', 'timeFrame': 'Baseline, Weeks 16, 20, 24', 'description': 'Hemoglobin response (HR) is defined as a ≥1.5 g/dL (0.93 mmol/L) increase in Hb concentration from baseline that is sustained at 2 or more scheduled assessments at Weeks 16, 20, and 24. The baseline Hb concentration is the average of all available Hb concentrations for a participant during the Screening Period up to the first dose of study treatment. As pre-specified in the protocol, the data for this outcome measure is summarized between the active arm vs the placebo arm (AG-348 5 mg, 20 mg and 50 mg arms are analyzed and reported together in comparison to Placebo).'}], 'secondaryOutcomes': [{'measure': 'Average Change From Baseline in Hb Concentration at Weeks 16, 20 and 24', 'timeFrame': 'Baseline, Weeks 16, 20, 24', 'description': 'This is the change in Hb concentration at Weeks 16, 20 and 24 compared to baseline. Data presented represents the value of the change from baseline averaged over Weeks 16, 20 and 24. Baseline was defined as the average of all screening assessments within 45 (42+3) days before randomization for participants randomized and not dosed or before start of study treatment for participants randomized and dosed. As pre-specified in the protocol, the data for this outcome measure is summarized between the active arm vs the placebo arm (AG-348 5 mg, 20 mg and 50 mg arms are analyzed and reported together in comparison to Placebo).'}, {'measure': 'Maximum Change From Baseline in Hb Concentration', 'timeFrame': 'Baseline, up to Week 24', 'description': 'This is the maximum change from baseline in Hb concentration up to Week 24. As pre-specified in the protocol, the data for this outcome measure is summarized between the active arm vs the placebo arm (AG-348 5 mg, 20 mg and 50 mg arms are analyzed and reported together in comparison to Placebo).'}, {'measure': 'Time to Achieve an Increase in Hb Concentration of 1.5 g/dL or More', 'timeFrame': 'Baseline, up to Week 24', 'description': 'This is the time taken to first achieve an increase of hemoglobin concentration of 1.5 g/dL or more from baseline. As pre-specified in the protocol, the data for this outcome measure is summarized between the active arm vs the placebo arm (AG-348 5 mg, 20 mg and 50 mg arms are analyzed and reported together in comparison to Placebo).'}, {'measure': 'Average Change From Baseline in Indirect Bilirubin at Weeks 16, 20 and 24', 'timeFrame': 'Baseline, Weeks 16, 20, 24', 'description': 'The change from baseline in indirect bilirubin levels was summarized. Indirect bilirubin is a marker for hemolysis. Data presented represents the value of the change from baseline averaged over Weeks 16, 20 and 24. Baseline was defined as the average of all screening assessments within 45 (42+3) days before randomization for participants randomized and not dosed or before the start of study treatment for participants randomized and dosed. As pre-specified in the protocol, the data for this outcome measure is summarized between the active arm vs the placebo arm (AG-348 5 mg, 20 mg and 50 mg arms are analyzed and reported together in comparison to Placebo).'}, {'measure': 'Average Change From Baseline in Lactic Acid Dehydrogenase (LDH) at Weeks 16, 20 and 24', 'timeFrame': 'Baseline, Weeks 16, 20, 24', 'description': 'The change from baseline in LDH levels was summarized. LDH is a marker for hemolysis. Data presented represents the value of the change from baseline averaged over Weeks 16, 20 and 24. Baseline was defined as the average of all screening assessments within 45 (42+3) days before randomization for participants randomized and not dosed or before the start of study treatment for participants randomized and dosed. As pre-specified in the protocol, the data for this outcome measure is summarized between the active arm vs the placebo arm (AG-348 5 mg, 20 mg and 50 mg arms are analyzed and reported together in comparison to Placebo).'}, {'measure': 'Average Change From Baseline in Haptoglobin at Weeks 16, 20 and 24', 'timeFrame': 'Baseline, Weeks 16, 20, 24', 'description': 'The change from baseline in haptoglobin levels was summarized. Haptoglobin levels are markers for hemolysis. Data presented represents the value of the change from baseline averaged over Weeks 16, 20 and 24. Baseline was defined as the average of all screening assessments within 45 (42+3) days before randomization for participants randomized and not dosed or before the start of study treatment for participants randomized and dosed. As pre-specified in the protocol, the data for this outcome measure is summarized between the active arm vs the placebo arm (AG-348 5 mg, 20 mg and 50 mg arms are analyzed and reported together in comparison to Placebo).'}, {'measure': 'Average Change From Baseline in Reticulocyte Percentages at Weeks 16, 20 and 24', 'timeFrame': 'Baseline, Weeks 16, 20, 24', 'description': 'The change from baseline in reticulocyte percentage was summarized. Reticulocyte levels are markers for hematopoietic activity. Data presented represents the value of the change from baseline averaged over Weeks 16, 20 and 24. Baseline was defined as the average of all screening assessments within 45 (42+3) days before randomization for participants randomized and not dosed or before the start of study treatment for participants randomized and dosed. As pre-specified in the protocol, the data for this outcome measure is summarized between the active arm vs the placebo arm (AG-348 5 mg, 20 mg and 50 mg arms are analyzed and reported together in comparison to Placebo).'}, {'measure': 'Change From Baseline in Pyruvate Kinase Deficiency Diary (PKDD) Score at Week 24', 'timeFrame': 'Baseline, Week 24', 'description': 'The PKDD is a 7-item patient reported outcome (PRO) measure of the core signs and symptoms associated with PK deficiency in adults. Participants rate their experience with symptoms of PK deficiency on the present day. The symptoms include those associated with tiredness, jaundice, bone pain, shortness of breath, and energy level. The score ranges from 25 to 76, with higher scores indicating a higher disease burden. The change from baseline in PKDD weekly scores was evaluated. A negative change from baseline indicates a lower disease burden. As pre-specified in the protocol, the data for this outcome measure is summarized between the active arm vs the placebo arm (AG-348 5 mg, 20 mg and 50 mg arms are analyzed and reported together in comparison to Placebo).'}, {'measure': 'Change From Baseline in Pyruvate Kinase Deficiency Impact Assessment (PKDIA) Score at Week 24', 'timeFrame': 'Baseline, Week 24', 'description': 'The PKDIA is a 12-item patient reported outcome (PRO) measure of the common impacts of PK deficiency on activities of daily living. Participants rate how PK deficiency has impacted aspects of daily living in the past 7 days, including impacts on relationships; perceived appearance; work performance; and leisure, social, mental, and physical activities. The score range is 30 to 76, with higher scores indicating a higher disease burden. The change from baseline in PKDIA scores was evaluated. A negative change from baseline indicates a lower disease burden. As pre-specified in the protocol, the data for this outcome measure is summarized between the active arm vs the placebo arm (AG-348 5 mg, 20 mg and 50 mg arms are analyzed and reported together in comparison to Placebo).'}, {'measure': 'Percentage of Participants With Adverse Events', 'timeFrame': 'From signing of informed consent form to the end of study, including follow-up (up to Day 197)', 'description': 'An AE is any untoward medical occurrence in a participant or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the study 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.'}, {'measure': 'Area Under the Curve From Time 0 to the Last Quantifiable Concentration [AUC(0-last)] for AG-348 at Week 12', 'timeFrame': 'Pre-dose, 30 minutes and 1, 2, 4 and 8 hours post-dose on Day 85 (Week 12)'}, {'measure': 'Maximum Plasma Concentration (Cmax) for AG-348', 'timeFrame': 'Pre-dose, 30 minutes and 1, 2, 4 and 8 hours post-dose on Day 85 (Week 12)'}, {'measure': 'Time to Cmax (Tmax) for AG-348', 'timeFrame': 'Pre-dose, 30 minutes and 1, 2, 4 and 8 hours post-dose on Day 85 (Week 12)'}, {'measure': 'Time to Last Measurable Concentration (Tlast) for AG-348', 'timeFrame': 'Pre-dose, 30 minutes and 1, 2, 4 and 8 hours post-dose on Day 85 (Week 12)'}, {'measure': 'Exposure-Response Relationship of Adverse Event (Hot Flush) and AG-348 Concentration and Relevant AG-348 Pharmacokinetic Parameters', 'timeFrame': 'From first dose of mitapivat to the end of study, including follow-up (up to Day 197)', 'description': 'Predicted probability of experiencing all grade hot flush at the doses of 5, 20, and 50 mg mitapivat BID based on exposure-response model.'}, {'measure': 'Exposure-Response Relationship Between Safety Parameters (Sex Hormone in Male Subjects) and AG-348 Concentration and Relevant AG-348 Pharmacokinetic Parameters', 'timeFrame': 'Baseline, Week 24', 'description': 'Predicted percent change from baseline at Week 24 in the sex hormone measures (total testosterone, free testosterone, and estrone) at the doses of 5, 20, and 50 mg mitapivat BID in male participants.'}]}, 'oversightModule': {'oversightHasDmc': True, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['Pyruvate Kinase Deficiency', 'Anemia, Hemolytic']}, 'referencesModule': {'references': [{'pmid': '38330179', 'type': 'DERIVED', 'citation': 'van Beers EJ, Al-Samkari H, Grace RF, Barcellini W, Glenthoj A, DiBacco M, Wind-Rotolo M, Xu R, Beynon V, Patel P, Porter JB, Kuo KHM. Mitapivat improves ineffective erythropoiesis and iron overload in adult patients with pyruvate kinase deficiency. Blood Adv. 2024 May 28;8(10):2433-2441. doi: 10.1182/bloodadvances.2023011743.'}, {'pmid': '37943362', 'type': 'DERIVED', 'citation': 'Andrae DA, Grace RF, Jewett A, Foster B, Klaassen RJ, Salek S, Li J, Tai F, Boscoe AN, Zagadailov E. Psychometric validation of the Pyruvate Kinase Deficiency Diary and Pyruvate Kinase Deficiency Impact Assessment in adults in the phase 3 ACTIVATE trial. J Patient Rep Outcomes. 2023 Nov 9;7(1):112. doi: 10.1186/s41687-023-00650-3.'}, {'pmid': '36594181', 'type': 'DERIVED', 'citation': 'Al-Samkari H, Grace RF, Glenthoj A, Andres O, Barcellini W, Galacteros F, Kuo KHM, Layton DM, Morado Arias M, Viprakasit V, Dong Y, Tai F, Hawkins P, Gheuens S, Morales-Arias J, Gilroy KS, Porter JB, van Beers EJ. Early-onset reduced bone mineral density in patients with pyruvate kinase deficiency. Am J Hematol. 2023 Mar;98(3):E57-E60. doi: 10.1002/ajh.26830. Epub 2023 Jan 9. No abstract available.'}, {'pmid': '35417638', 'type': 'DERIVED', 'citation': 'Al-Samkari H, Galacteros F, Glenthoj A, Rothman JA, Andres O, Grace RF, Morado-Arias M, Layton DM, Onodera K, Verhovsek M, Barcellini W, Chonat S, Judge MP, Zagadailov E, Xu R, Hawkins P, Beynon V, Gheuens S, van Beers EJ; ACTIVATE Investigators. Mitapivat versus Placebo for Pyruvate Kinase Deficiency. N Engl J Med. 2022 Apr 14;386(15):1432-1442. doi: 10.1056/NEJMoa2116634.'}, {'pmid': '31974203', 'type': 'DERIVED', 'citation': 'Rab MAE, Van Oirschot BA, Kosinski PA, Hixon J, Johnson K, Chubukov V, Dang L, Pasterkamp G, Van Straaten S, Van Solinge WW, Van Beers EJ, Kung C, Van Wijk R. AG-348 (Mitapivat), an allosteric activator of red blood cell pyruvate kinase, increases enzymatic activity, protein stability, and ATP levels over a broad range of PKLR genotypes. Haematologica. 2021 Jan 1;106(1):238-249. doi: 10.3324/haematol.2019.238865.'}]}, 'descriptionModule': {'briefSummary': 'Study AG348-C-006 evaluated the efficacy and safety of orally administered AG-348 as compared with placebo in participants with pyruvate kinase (PK) deficiency, who were not regularly receiving blood transfusions. Participants were randomized 1:1 to receive either AG-348 or a matching placebo.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Informed consent;\n* Male or female, aged 18 years or older;\n* Documented clinical laboratory confirmation of pyruvate kinase (PK) deficiency, defined as documented presence of at least 2 mutant alleles in the PKLR gene, of which at least 1 is a missense mutation;\n* Hemoglobin (Hb) concentration less than or equal to 10.0 grams per deciliter (g/dL) regardless of gender (average of at least 2 Hb measurements \\[separated by a minimum of 7 days\\] during the Screening Period)\n* Considered not regularly transfused, defined as having had no more than 4 transfusion episodes in the 12-month period up to the first day of study treatment and no transfusions in the 3 months prior to the first day of study treatment;\n* Received at least 0.8 mg oral folic acid daily for at least 21 days prior to the first dose of study treatment, to be continued daily during study participation.\n* Adequate organ function;\n* Women of reproductive potential, have a negative serum pregnancy test;\n* For women of reproductive potential as well as men with partners who are women of reproductive potential, be abstinent as part of their usual lifestyle, or agree to use 2 forms of contraception, 1 of which must be considered highly effective, from the time of giving informed consent, during the study, and for 28 days following the last dose of study treatment for women and 90 days for men following the last dose of study treatment;\n* Willing to comply with all study procedures for the duration of the study;\n\nExclusion Criteria:\n\n* Homozygous for the R479H mutation or have 2 non-missense mutations, without the presence of another missense mutation, in the PKLR gene;\n* Significant medical condition that confers an unacceptable risk to participating in the study, and/or that could confound the interpretation of the study data;\n* Splenectomy scheduled during the study treatment period or have undergone splenectomy within 12 months prior to signing informed consent;\n* Currently enrolled in another therapeutic clinical trial involving ongoing therapy with any investigational or marketed product or placebo. Prior and subsequent participation in the PK Deficiency Natural History Study (NHS) (NCT02053480) or PK Deficiency Registry is permitted however, concurrent participation is not; participants enrolling in this current study will be expected to temporarily suspend participation in the NHS or Registry;\n* Exposure to any investigational drug, device, or procedure within 3 months prior to the first dose of study treatment;\n* Prior treatment with a pyruvate kinase activator;\n* Prior bone marrow or stem cell transplant;\n* Currently pregnant or breastfeeding;\n* History of major surgery within 6 months of signing informed consent;\n* Currently receiving medications that are strong inhibitors of cytochrome P450 (CYP)3A4, strong inducers of CYP3A4, strong inhibitors of P-glycoprotein (P-gp), or digoxin (a P-gp sensitive substrate medication) that have not been stopped for a duration of at least 5 days or a timeframe equivalent to 5 half-lives (whichever is longer) prior to the first dose of study treatment;\n* Currently receiving hematopoietic stimulating agents that have not been stopped for a duration of at least 28 days prior to the first dose of study treatment;\n* History of allergy to sulfonamides if characterized by acute hemolytic anemia, drug induced liver injury, anaphylaxis, rash of erythema multiforme type or Stevens-Johnson syndrome, cholestatic hepatitis, or other serious clinical manifestations;\n* History of allergy to AG-348 or its excipients;\n* Currently receiving anabolic steroids, including testosterone preparations, within 28 days prior to treatment.'}, 'identificationModule': {'nctId': 'NCT03548220', 'briefTitle': 'A Study to Evaluate Efficacy and Safety of AG-348 in Not Regularly Transfused Adult Participants With Pyruvate Kinase Deficiency (PKD)', 'organization': {'class': 'INDUSTRY', 'fullName': 'Agios Pharmaceuticals, Inc.'}, 'officialTitle': 'A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of AG-348 in Not Regularly Transfused Adult Subjects With Pyruvate Kinase Deficiency', 'orgStudyIdInfo': {'id': 'AG348-C-006'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'PLACEBO_COMPARATOR', 'label': 'Placebo', 'description': 'Participants received a matching placebo to AG-348 tablets, for a period of 12 weeks as an optimized dose. This was followed by matching placebo further, for a period of 12 weeks as a fixed-dose.', 'interventionNames': ['Drug: Placebo']}, {'type': 'EXPERIMENTAL', 'label': 'AG-348, 5 mg', 'description': 'Participants received AG-348 tablets, 5 milligrams (mg) twice daily (BID), administered orally, for 4 weeks as a starting dose, followed by two potential sequential dose level increases to 20 mg and 50 mg BID at Weeks 4 and 8 respectively as determined by the investigator based on safety and efficacy. The optimized dose for each participant was determined as 5 mg BID at Week 12, and participants then received that optimized dose for a period of 12 weeks as a fixed dose.', 'interventionNames': ['Drug: AG-348']}, {'type': 'EXPERIMENTAL', 'label': 'AG-348, 20 mg', 'description': 'Participants received AG-348 tablets, 5 mg BID, administered orally, for 4 weeks as a starting dose, followed by two potential sequential dose level increases to 20 mg and 50 mg BID at Weeks 4 and 8 respectively as determined by the investigator based on safety and efficacy. The optimized dose for each participant was determined as 20 mg BID at Week 12, and participants then received that optimized dose for a period of 12 weeks as a fixed dose.', 'interventionNames': ['Drug: AG-348']}, {'type': 'EXPERIMENTAL', 'label': 'AG-348, 50 mg', 'description': 'Participants received AG-348 tablets, 5 mg BID, administered orally, for 4 weeks as a starting dose, followed by two potential sequential dose level increases to 20 mg and 50 mg BID at Weeks 4 and 8 respectively as determined by the investigator based on safety and efficacy. The optimized dose for each participant was determined as 50 mg BID at Week 12, and participants then received that optimized dose for a period of 12 weeks as a fixed dose.', 'interventionNames': ['Drug: AG-348']}], 'interventions': [{'name': 'Placebo', 'type': 'DRUG', 'description': 'Placebo matching AG-348 tablets, administered to maintain the blind.', 'armGroupLabels': ['Placebo']}, {'name': 'AG-348', 'type': 'DRUG', 'description': 'AG-348 tablets.', 'armGroupLabels': ['AG-348, 20 mg', 'AG-348, 5 mg', 'AG-348, 50 mg']}]}, 'contactsLocationsModule': {'locations': [{'zip': '72205', 'city': 'Little Rock', 'state': 'Arkansas', 'country': 'United States', 'facility': 'University of Arkansas for Medical Sciences', 'geoPoint': {'lat': 34.74648, 'lon': -92.28959}}, {'zip': '30322', 'city': 'Atlanta', 'state': 'Georgia', 'country': 'United States', 'facility': 'Emory University', 'geoPoint': {'lat': 33.749, 'lon': -84.38798}}, {'zip': '46260', 'city': 'Indianapolis', 'state': 'Indiana', 'country': 'United States', 'facility': 'Indiana Hemophilia and Thrombosis Center', 'geoPoint': {'lat': 39.76838, 'lon': -86.15804}}, {'zip': '02114', 'city': 'Boston', 'state': 'Massachusetts', 'country': 'United States', 'facility': 'Massachusetts General Hospital', 'geoPoint': {'lat': 42.35843, 'lon': -71.05977}}, {'zip': '02115', 'city': 'Boston', 'state': 'Massachusetts', 'country': 'United States', 'facility': "The Children's Hospital Corporation d/b/a Boston's Children Hospital", 'geoPoint': {'lat': 42.35843, 'lon': -71.05977}}, {'zip': '48304', 'city': 'Detroit', 'state': 'Michigan', 'country': 'United States', 'facility': "Wayne State University School of Medicine, Children's Hospital of Michigan", 'geoPoint': {'lat': 42.33143, 'lon': -83.04575}}, {'zip': '27705', 'city': 'Durham', 'state': 'North Carolina', 'country': 'United States', 'facility': 'Duke University', 'geoPoint': {'lat': 35.99403, 'lon': -78.89862}}, {'zip': '27858', 'city': 'Greenville', 'state': 'North Carolina', 'country': 'United States', 'facility': 'East Carolina University', 'geoPoint': {'lat': 35.61266, 'lon': -77.36635}}, {'zip': '45229', 'city': 'Cincinnati', 'state': 'Ohio', 'country': 'United States', 'facility': "Cincinnati Children's Hospital Medical Center", 'geoPoint': {'lat': 39.12711, 'lon': -84.51439}}, {'zip': '77030', 'city': 'Houston', 'state': 'Texas', 'country': 'United States', 'facility': 'Houston Methodist Research Institute', 'geoPoint': {'lat': 29.76328, 'lon': -95.36327}}, {'zip': '84112', 'city': 'Salt Lake City', 'state': 'Utah', 'country': 'United States', 'facility': "Primary Children's Hospital Univ. of Utah", 'geoPoint': {'lat': 40.76078, 'lon': -111.89105}}, {'zip': '98109', 'city': 'Seattle', 'state': 'Washington', 'country': 'United States', 'facility': 'Seattle Cancer Care Alliance', 'geoPoint': {'lat': 47.60621, 'lon': -122.33207}}, {'city': 'São Paulo', 'country': 'Brazil', 'facility': 'Hospital Central da Faculdade de Medicina USP Cidade Universitaria', 'geoPoint': {'lat': -23.5475, 'lon': -46.63611}}, {'zip': 'L8S 4LB', 'city': 'Hamilton', 'country': 'Canada', 'facility': 'McMaster University - Health Sciences Centre', 'geoPoint': {'lat': 43.25011, 'lon': -79.84963}}, {'zip': 'M5G 2C4', 'city': 'Toronto', 'country': 'Canada', 'facility': 'Toronto General Hospital, University Health Network', 'geoPoint': {'lat': 43.70643, 'lon': -79.39864}}, {'city': 'Prague', 'country': 'Czechia', 'facility': 'Institute of Hematology and Blood Transfusion', 'geoPoint': {'lat': 50.08804, 'lon': 14.42076}}, {'zip': '2730', 'city': 'Herlev', 'country': 'Denmark', 'facility': 'University of Copenhagen, Herlev Hospital', 'geoPoint': {'lat': 55.72366, 'lon': 12.43998}}, {'zip': '80054', 'city': 'Amiens', 'country': 'France', 'facility': 'CHU Amiens Picardie', 'geoPoint': {'lat': 49.9, 'lon': 2.3}}, {'city': 'Bordeaux', 'country': 'France', 'facility': 'Hopital Saint-Andre', 'geoPoint': {'lat': 44.84124, 'lon': -0.58046}}, {'zip': '94010', 'city': 'Créteil', 'country': 'France', 'facility': 'Hôpital Henri-Mondor', 'geoPoint': {'lat': 48.79266, 'lon': 2.46569}}, {'zip': '13385', 'city': 'Marseille', 'country': 'France', 'facility': 'Hôpital de la Timone', 'geoPoint': {'lat': 43.29695, 'lon': 5.38107}}, {'city': 'Toulouse', 'country': 'France', 'facility': 'Institut Claudius Regaud', 'geoPoint': {'lat': 43.60426, 'lon': 1.44367}}, {'city': 'Berlin', 'country': 'Germany', 'facility': 'Charite University Medicine', 'geoPoint': {'lat': 52.52437, 'lon': 13.41053}}, {'zip': '97080', 'city': 'Würzburg', 'country': 'Germany', 'facility': 'Universitätsklinikum Würzburg', 'geoPoint': {'lat': 49.79391, 'lon': 9.95121}}, {'zip': '16128', 'city': 'Genova', 'country': 'Italy', 'facility': 'Ospedale Galliera', 'geoPoint': {'lat': 45.21604, 'lon': 11.87211}}, {'zip': '20122', 'city': 'Milan', 'country': 'Italy', 'facility': "Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico", 'geoPoint': {'lat': 42.78235, 'lon': 12.59836}}, {'zip': '80138', 'city': 'Napoli', 'country': 'Italy', 'facility': 'AOU Policlinico, Università della Campania "Luigi Vanvitelli"', 'geoPoint': {'lat': 40.87618, 'lon': 14.5195}}, {'city': 'Sendai', 'state': 'Miyagi', 'country': 'Japan', 'facility': 'Tohoku University Hospital', 'geoPoint': {'lat': 38.26667, 'lon': 140.86667}}, {'city': 'Kyoto', 'country': 'Japan', 'facility': 'Kyoto Katsura Hospital', 'geoPoint': {'lat': 35.02107, 'lon': 135.75385}}, {'city': 'Mie', 'country': 'Japan', 'facility': 'Agios Investigative Site', 'geoPoint': {'lat': 32.96667, 'lon': 131.58333}}, {'zip': '534-0021', 'city': 'Osaka', 'country': 'Japan', 'facility': 'Osaka City General Hospital', 'geoPoint': {'lat': 34.69379, 'lon': 135.50107}}, {'city': 'Osaka', 'country': 'Japan', 'facility': 'Kansai Medical University, Department of Pediatrics, Hirakata Hospital', 'geoPoint': {'lat': 34.69379, 'lon': 135.50107}}, {'city': 'Tokyo', 'country': 'Japan', 'facility': 'Toho University Omori Medical Center', 'geoPoint': {'lat': 35.6895, 'lon': 139.69171}}, {'zip': '3584', 'city': 'Utrecht', 'country': 'Netherlands', 'facility': 'Universitair Medisch Centrum Utrecht', 'geoPoint': {'lat': 52.09083, 'lon': 5.12222}}, {'zip': '42415', 'city': 'Daegu 705-703', 'country': 'South Korea', 'facility': 'Yeungnam University Hospital'}, {'zip': '08035', 'city': 'Barcelona', 'country': 'Spain', 'facility': "Hospital U. Vall d'Hebron Servicio de Hematología Clínica", 'geoPoint': {'lat': 41.38879, 'lon': 2.15899}}, {'zip': '30120', 'city': 'El Palmar', 'country': 'Spain', 'facility': 'Hospital Clinico Universitario Virgen de la Arricaxa', 'geoPoint': {'lat': 39.31305, 'lon': -0.3174}}, {'zip': '28046', 'city': 'Madrid', 'country': 'Spain', 'facility': 'Hospital Universitario La Paz', 'geoPoint': {'lat': 40.4165, 'lon': -3.70256}}, {'zip': '1011', 'city': 'Lausanne', 'country': 'Switzerland', 'facility': 'Centre Hospitalier Universitaire Vaudois (CHUV)', 'geoPoint': {'lat': 46.516, 'lon': 6.63282}}, {'zip': '10700', 'city': 'Bangkok', 'country': 'Thailand', 'facility': 'Department of Paediatrics and Thalassaemia Center, Faculty of Medicine Siriraj', 'geoPoint': {'lat': 13.75398, 'lon': 100.50144}}, {'city': 'Ankara', 'country': 'Turkey (Türkiye)', 'facility': 'Hacettepe University', 'geoPoint': {'lat': 39.91987, 'lon': 32.85427}}, {'zip': '94609', 'city': 'Cambridge', 'country': 'United Kingdom', 'facility': "Addenbrooke's Hospital", 'geoPoint': {'lat': 52.2, 'lon': 0.11667}}, {'zip': 'L7 8XP', 'city': 'Liverpool', 'country': 'United Kingdom', 'facility': 'The Royal Liverpool and Broadgreen University', 'geoPoint': {'lat': 53.41058, 'lon': -2.97794}}, {'zip': 'W12 0NN', 'city': 'London', 'country': 'United Kingdom', 'facility': 'Imperial College Healthcare NHS Trust, Hammersmith Hospital', 'geoPoint': {'lat': 51.50853, 'lon': -0.12574}}, {'zip': 'W12 0NN', 'city': 'London', 'country': 'United Kingdom', 'facility': 'University College London', 'geoPoint': {'lat': 51.50853, 'lon': -0.12574}}, {'zip': 'M13 9WL', 'city': 'Manchester', 'country': 'United Kingdom', 'facility': 'Manchester Royal Infirmary', 'geoPoint': {'lat': 53.48095, 'lon': -2.23743}}], 'overallOfficials': [{'name': 'Medical Affairs', 'role': 'STUDY_CHAIR', 'affiliation': 'Agios Pharmaceuticals, Inc.'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Agios Pharmaceuticals, Inc.', 'class': 'INDUSTRY'}, 'responsibleParty': {'type': 'SPONSOR'}}}}