Extension Study of AG-348 in Adult Participants With Pyru... | NCT03853798 | Trialant
NCT03853798
Sponsor
Agios Pharmaceuticals, Inc.
Status
Completed
Last Update Posted
Nov 18, 2025Actual
Enrollment
90Actual
Phase
Phase 3
Conditions
Pyruvate Kinase Deficiency
Interventions
Mitapivat
Countries
United States
Brazil
Canada
Denmark
France
Germany
Ireland
Italy
Japan
Netherlands
South Korea
Spain
Switzerland
Thailand
Turkey (Türkiye)
United Kingdom
Protocol Section
Identification Module
NCT ID
NCT03853798
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
AG348-C-011
Secondary IDs
ID
Type
Description
Link
2018-003459-39
EudraCT Number
Brief Title
Extension Study of AG-348 in Adult Participants With Pyruvate Kinase Deficiency Previously Enrolled in AG-348-006 or AG348-C-007
Official Title
An Open-Label, Multicenter, Extension Study of AG-348 in Adult Subjects With Pyruvate Kinase Deficiency Previously Enrolled in AG-348 Studies
Acronym
Not provided
Organization
Agios Pharmaceuticals, Inc.INDUSTRY
Status Module
Record Verification Date
Nov 2025
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Mar 21, 2019Actual
Primary Completion Date
Jul 3, 2024Actual
Completion Date
Jul 3, 2024Actual
First Submitted Date
Feb 22, 2019
First Submission Date that Met QC Criteria
Feb 22, 2019
First Posted Date
Feb 26, 2019Actual
Results Waived
Not provided
Results First Submitted Date
Jul 2, 2025
Results First Submitted that Met QC Criteria
Nov 4, 2025
Results First Posted Date
Nov 18, 2025Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
Nov 4, 2025
Last Update Posted Date
Nov 18, 2025Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
Agios Pharmaceuticals, Inc.INDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
No
Is FDA Regulated Drug
Yes
Is FDA Regulated Device
No
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
Brief Summary
This is an open-label, multicenter, extension study to evaluate the long-term safety, tolerability, and efficacy of treatment with mitapivat in participants who were previously enrolled in Study AG348-C-006 or Study AG348-C-007.
Detailed Description
Not provided
Conditions Module
Conditions
Pyruvate Kinase Deficiency
Keywords
Not provided
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 3
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
90Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Cohort 1
Experimental
Participants who received placebo in Study AG348-C-006 and met the eligibility criteria of this extension study were enrolled to receive mitapivat 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 at Week 12, and participants then received that optimized dose for a period of 12 weeks (Weeks 13-24) as a fixed dose and from Week 25 to Week 193, until study withdrawal, or the study was closed.
Drug: Mitapivat
Cohort 2
Experimental
Participants who received mitapivat at a dose of 5 mg, 20 mg, or 50 mg, BID, in the fixed dose period of Study AG348-C-006 and met the eligibility criteria of this extension study continued to receive the same mitapivat dose up to Week 193 or until study withdrawal, or the study was closed.
Drug: Mitapivat
Cohort 3
Experimental
Participants who received mitapivat at a dose of 5 mg, 20 mg, or 50 mg, BID, in the fixed dose period of Study AG348-C-007 and met the eligibility criteria of this extension study continued to receive the same mitapivat dose up to Week 193 or until study withdrawal, or the study was closed.
Drug: Mitapivat
Interventions
Name
Type
Description
Arm Group Labels
Other Names
Mitapivat
Drug
Tablets
Cohort 1
Cohort 2
Cohort 3
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
All Cohorts: Number of Participants With at Least One Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Related TEAEs and TEAEs With Severity Greater Than or Equal to Grade 3
A clinical adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the study drug. TEAEs are AEs with an initial onset date during the on-treatment period or worsening from baseline and include both serious and non-serious TEAEs. Severity of AEs was evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE; Version 4.03): grade 1: mild; grade 2: moderate; grade 3: severe or medically significant but not immediately life-threatening; grade 4: life threatening or disabling; grade 5: death related to AE.
Up to 197 weeks
All Cohorts: Number of Participants With TEAEs Leading to Dose Reduction, Treatment Interruption and Treatment Discontinuation
A clinical AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the study drug. TEAEs are AEs with an initial onset date during the on-treatment period or worsening from baseline and include both serious and non-serious TEAEs. Number of participants with TEAEs leading to dose reduction, treatment interruption and treatment discontinuation are reported.
Up to 197 weeks
All Cohorts: Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters Reported as Grade Greater Than or Equal to (≥)3 TEAEs
Clinical laboratory assessments including hematology, clinical chemistry, triglycerides, urate, coagulation, urinalysis, and liver function tests were performed in the study. Clinically significant treatment-emergent laboratory abnormalities were graded according to the NCI CTCAE; Version 4.03: grade 1: mild; grade 2: moderate; grade 3: severe or medically significant but not immediately life-threatening; grade 4: life threatening or disabling; grade 5: death related to AE. Clinical significance was determined based on the judgment of the Investigator.
Secondary Outcomes
Measure
Description
Time Frame
Cohort 1: Percentage of Participants Who Achieved a Hemoglobin (Hb) Response
The Hb response was defined as a greater than or equal to (≥)1.5 grams per deciliter (g/dL) (0.93 millimoles per liter [mmol/L]) increase in Hb concentration from baseline that is sustained at 2 or more scheduled assessments, excluding those within 2 months (61 days) of transfusion. The baseline value for cohort 1 participants was the average of all available measurements from the central laboratory within 45 (42+3) days before start of study treatment in study AG348-C-011, excluding values within 61 days after a transfusion, or the baseline value from study AG348-C-006 if no assessment is available.
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Inclusion Criteria:
Be willing and able to comply with study visits and procedures.
Have signed written informed consent prior to participating in this extension study.
Have completed either antecedent study AG348-C-006 or AG348-C-007 through the Part 2 Week 24 Visit.
Cohorts 2 and 3: Have demonstrated clinical benefit from mitapivat treatment in the antecedent study, in the opinion of the Investigator.
For women of reproductive potential, have a negative pregnancy test during screening of this extension study.
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 drug for women and 90 days following the last dose of study drug for men.
Exclusion Criteria:
Have a significant medical condition (including clinically significant laboratory abnormality) that developed during his/her antecedent AG- 348 study that confers an unacceptable risk to participating in this extension study, that could confound the interpretation of the study data, and/or that compromises the ability of the participant to complete study visits and procedures.
Are currently pregnant or breastfeeding.
Have a splenectomy scheduled during the study treatment period.
Meet the withdrawal criteria of his/her antecedent mitapivat study during screening of this extension study.
Are currently receiving medications that are strong inhibitors of cytochrome P450 (CYP)3A4 that have not been stopped for a duration of at least 5 days or a time frame equivalent to 5 half-lives (whichever is longer) before start of study drug; or strong inducers of CYP3A4 that have not been stopped for a duration of at least 28 days or a time frame equivalent to 5 half-lives (whichever is longer) before start of study drug on this extension study.
Have received anabolic steroids, including testosterone preparations, within 28 days prior to start of study drug on this extension study.
Have received hematopoietic stimulating agents (eg, erythropoietins, granulocyte colony stimulating factors, thrombopoietins) within 28 days prior to start of study drug on this extension study.
Have exposure to any investigational drug other than mitapivat, device, or procedure within 3 months prior to start of study drug on this extension study.
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.
A total of 90 participants who had completed Study AG348-C-006 (NCT03548220) or AG348-C-007 (NCT03559699), were enrolled in this extension study to receive mitapivat treatment. Participants were assigned to Cohorts 1, 2 or 3 depending on the previous treatment received in the antecedent studies.
Recruitment Details
Participants were enrolled at 42 investigative sites in Denmark, France, Italy, Spain, Germany, United Kingdom, Netherlands, Ireland, Switzerland, United States, Canada, Japan, Korea, Thailand, Brazil and Turkey from 21 March 2019 to 03 July 2024.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
Cohort 1: 5 mg
Participants who received placebo in Study AG348-C-006 and met the eligibility criteria of this extension study were enrolled to receive mitapivat 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, which was followed for a period of 12 weeks (Weeks 13-24) as a fixed dose and then from Week 25 to Week 193, until study withdrawal, or the study was closed.
Periods
Title
Milestones
Reasons Not Completed
Overall Study
Type
Comment
Milestone Data
STARTED
Baseline Characteristics Module
Baseline Analysis Population Description
Outcome Measures Module
Outcome Measures
Adverse Events Module
Frequency Threshold
5
More Info Module
Limitations and Caveats
Not provided
Annotation Section
No data available
No data is available for this block.
Document Section
Large Document Module
Document Has No Statistical Analysis Plan (SAP)
Not provided
Uploaded Document Information
Type
Includes Protocol
Includes SAP
Includes ICF
Document Label
Document Date
Document Uploaded Date
Document File Name
Prot
Yes
No
No
Study Protocol
Jul 19, 2022
Jul 1, 2025
Derived Section
Miscellaneous Info Module
Version Holder
Jul 10, 2026
Removed Countries
Czechia
Portugal
Submission Tracking
Estimated Results First Submitted Date
Not provided
Condition Browse Module
MeSH Terms
Intervention Browse Module
MeSH Terms
Non-Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
Not provided
Primary Purpose
Treatment
Observational Model
Not provided
Time Perspective
Not provided
Masking Info
Masking
None (Open Label)
Masking Description
Not provided
Who Masked
Not provided
AG-348
AG-348 sulfate hydrate
Mitapivat sulfate
Up to 197 weeks
All Cohorts: Number of Participants With Clinically Significant Abnormalities in Vital Signs Measurements and Physical Examinations Reported as TEAEs
Vital signs and physical examinations including height, weight, body mass index (BMI), systolic blood pressure, diastolic blood pressure, pulse rate, temperature were assessed. Number of participants who experienced clinically significant abnormalities in vital signs and physical examinations as TEAEs were reported. Clinical significance was determined based on the judgment of the Investigator.
Up to 197 weeks
All Cohorts: Number of Participants With Clinically Significant Abnormalities in Bone Mineral Density (BMD)
BMD was measured by dual-energy X-ray absorptiometry (DXA) scans during the study. Number of participants with clinically significant abnormalities were reported. Clinical significance was determined based on the judgment of the Investigator.
Up to 192 weeks
All Cohorts: Change From Baseline in Adjusted Spine T-score
T-score of adjusted spine were assessed by DXA scans. The T-score is the number of standard deviations that bone density is above or below the average. A score of ≥ -1 indicates normal bone density; score between < -1 and > -2.5 indicates a sign of osteopenia (bone density below normal), and score of ≤ -2.5 indicates a sign of osteoporosis.
Baseline, Week 192
All Cohorts: Change From Baseline in Adjusted Spine Z-score
The Z-score is a statistical measure to describe whether a value was above or below the standard. A Z-score of 0 is equal to the standard. Lower numbers indicate values lower than the standard and higher numbers indicate values higher than the standard.
Baseline, Week 192
All Cohorts: Change From Baseline in Femoral Total T-score
T-score of femoral total were assessed by DXA scans. The T-score is the number of standard deviations that bone density is above or below the average. A score of ≥ -1 indicates normal bone density; score between < -1 and > -2.5 indicates a sign of osteopenia (bone density below normal), and score of ≤ -2.5 indicates a sign of osteoporosis.
Baseline, Week 192
All Cohorts: Change From Baseline in Femoral Total Z-score
The Z-score is a statistical measure to describe whether a value was above or below the standard. A Z-score of 0 is equal to the standard. Lower numbers indicate values lower than the standard and higher numbers indicate values higher than the standard.
Baseline, Week 192
All Cohorts: Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters Reported as TEAEs
The following ECG parameters including RR, PR, heart rate-corrected QT interval using the Fridericia's formula (QRS), QT, and QTc were assessed during the study. Number of Participants with clinically significant abnormalities in ECG parameters as TEAEs were reported. Clinical significance was determined based on the judgment of the Investigator.
Up to 197 weeks
Baseline up to Week 24
Cohort 1: Average Change From Baseline in Hb Concentration at Weeks 16, 20, and 24
The baseline value for participants was the average of all available measurements from the central laboratory within 45 (42+3) days before start of study treatment in study AG348-C-011, excluding values within 61 days after a transfusion, or the baseline value from study AG348-C-006 if no assessment is available. The mean of average change from baseline in Hb concentration across Weeks 16, 20 and 24 is reported.
Baseline, Weeks 16, 20, and 24
Cohort 1: Area Under the Plasma Concentration-Time Curve From Time Zero to 8-hours Post-dose (AUC0-8) of Mitapivat
Pre-dose, 0.5, 1, 2, 4, and 8 hours post-dose at Week 12
Cohort 1: Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUC0-last) of Mitapivat
Pre-dose, 0.5, 1, 2, 4, and 8 hours post-dose at Week 12
Cohort 1: Maximum Observed Plasma Concentration (Cmax) of Mitapivat
Pre-dose, 0.5, 1, 2, 4, and 8 hours post-dose at Week 12
Cohort 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Mitapivat
Pre-dose, 0.5, 1, 2, 4, and 8 hours post-dose at Week 12
Cohort 1: Time of Last Quantifiable Concentration (Tlast) of Mitapivat
Pre-dose, 0.5, 1, 2, 4, and 8 hours post-dose at Week 12
Cohort 1: Plasma Concentration (Ctrough) at the End of a Dosing Interval of Mitapivat
Pre-dose, 0.5, 1, 2, 4, and 8 hours post-dose at Week 12
Cohort 1: Exposure-response (E-R) Relationship Between Safety Parameters and Mitapivat Concentration and Relevant Mitapivat Pharmacokinetic Parameters
First dose to up to 24 weeks
Cohorts 1 and 2: Change From Baseline in Hb Concentration
The baseline value for cohort 1 participant was the average of all available measurements from the central laboratory within 45 (42+3) days before start of study treatment in study AG348-C-011, excluding values within 61 days after a transfusion, or the baseline value from study AG348-C-006 if no assessment was available. The baseline value for cohort 2 was from Study AG348-C-006.
Baseline, Week 192
Cohorts 1 and 2: Change From Baseline in Indirect Bilirubin
The baseline value for cohort 1 participant was the average of all available measurements from the central laboratory within 45 (42+3) days before start of study treatment in study AG348-C-011, excluding values within 61 days after a transfusion, or the baseline value from study AG348-C-006 if no assessment is available. The baseline value for cohort 2 was from Study AG348-C-006.
Baseline, Week 192
Cohorts 1 and 2: Change From Baseline in Lactate Dehydrogenase (LDH)
The baseline value for cohort 1 participant was the average of all available measurements from the central laboratory within 45 (42+3) days before start of study treatment in study AG348-C-011, excluding values within 61 days after a transfusion, or the baseline value from study AG348-C-006 if no assessment was available. The baseline value for cohort 2 was from Study AG348-C-006.
Baseline, Week 192
Cohorts 1 and 2: Change From Baseline in Haptoglobin Levels
The baseline value for Cohort 1 participant was the average of all available measurements from the central laboratory within 45 (42+3) days before start of study treatment in study AG348-C-011, excluding values within 61 days after a transfusion, or the baseline value from study AG348-C-006 if no assessment was available. The baseline value for Cohort 2 was from Study AG348-C-006.
Baseline, Week 192
Cohorts 1 and 2: Change From Baseline in Reticulocytes/Erythrocytes Ratio
The baseline value for Cohort 1 participants was the average of all available measurements from the central laboratory within 45 (42+3) days before start of study treatment in study AG348-C-011, excluding values within 61 days after a transfusion, or the baseline value from study AG348-C-006 if no assessment was available. The baseline value for Cohort 2 was from Study AG348-C-006.
Baseline, Week 192
Cohort 3: Change From Baseline in Number of Transfusion Episodes
Number of transfusions at baseline was determined based on the transfusion data during the 52 weeks before informed consent for Cohort 3. Number of on-study transfusions was based on transfusions collected up to the end of the fixed dose period and standardized to 52 weeks. The change from baseline in number of transfusions was summarized for Cohort 3.
Baseline, Week 192
Cohort 3: Change From Baseline in Number of Red Blood Cell (RBC) Units Transfused
Annualized total number of RBC units transfused (units/52-week) during the study, including data up to end of study (EOS), was the total number of RBC units transfused during the entire study*52 / [(date of EOS - date of start of study treatment + 1)/7]. Number of RBC units were determined based on the transfusion data during the 52 weeks before informed consent of the antecedent study for Cohort 3. Number of on-study RBC units was based on transfusion data collected up to the end of the fixed dose period and standardized to 52 weeks.
Baseline, Week 192
All Cohorts: Change From Baseline in Health-Related Quality of Life (HRQoL) Patient-Reported Outcome (PRO) Scores: Pyruvate Kinase Deficiency Diary (PKDD)
The PKDD is a validated, daily 7-item PRO instrument with a recall period of 24 hours that measures the core signs and symptoms associated with pyruvate kinase deficiency in adults. The symptoms include tiredness, jaundice, bone pain, shortness of breath, and energy level. PKDD daily scores were calculated based on the participant's response to the PKDD questionnaire. Score ranges from 25 to 76, with higher scores indicating more severe symptoms and a higher disease burden. The change from baseline in weekly mean scores was summarized. A negative change from baseline indicates a lower disease burden. Baseline of weekly mean score was defined as average of daily scores collected within 7 days before start of study treatment (mitapivat). For Cohort 1, last measurement before the start of study treatment in AG348-C-011 was used as baseline; if baseline was missing, then baseline value from AG348-C-006 was used. For Cohorts 2 & 3 baseline values from -006 and-007, respectively, were used.
Baseline, Week 24
All Cohorts: Change From Baseline in HRQoL PRO Scores: Pyruvate Kinase Deficiency Impact Assessment (PKDIA)
PKDIA is a 12-item PRO measure of common impacts of PK deficiency on activities of daily living. Participants rated how PK deficiency has impacted aspects of daily living in past 7 days, including impacts on relationships & leisure and social, mental, and physical activities. PKDIA score at each visit was based on 8 items that were retained after in-trial psychometric validation and calculated at each visit based on participant's response to PKDIA questionnaire. Score ranges from 30 to 76, with higher scores indicating higher disease burden. Negative change from baseline indicates lower disease burden. Baseline was defined as the last complete assessment (with no missing item in response) before start of study treatment. For Cohort 1, last measurement before start of study treatment in AG348-C-011 was used as baseline; if baseline was missing, then baseline value from AG348-C-006 was used. For Cohorts 2 and 3, the baseline values from 006 and 007, respectively, were used.
Institut Universitaire du Cancer de Toulouse - Oncopole
Toulouse
31100
France
Charite - UB - CVK - Medizinische Klinik
Berlin
10117
Germany
Universitätsklinik Würzburg
Würzburg
97080
Germany
St James's Hospital
Dublin
Ireland
Ospedale Galliera
Genova
16128
Italy
Osp Maggiore Policlinico Milano
Milan
20122
Italy
AORN Cardarelli
Naples
00165
Italy
Università della Campania "Luigi Vanvitelli"
Naples
80318
Italy
Mie University Hospital
Tsu
Mie-ken
514-8507
Japan
Tohoku University Hospital
Sendai
Miyagi
980-8574
Japan
Kyoto Katsura Hospital
Kyoto
615-8256
Japan
Kansai Medical University, Dep. of Pediatrics, Hirakata Hospital
Osaka
573-1010
Japan
Toho University Omori Medical Center
Tokyo
8541
Japan
Van Creveldkliniek
Utrecht
3508 GA
Netherlands
Yeungnam University Hospital
Daegu
705-703
South Korea
Hospital. U. Vall d'Hebron
Barcelona
08035
Spain
Hospital Universitario La Paz
Madrid
28046
Spain
Htal ClÃnico Universitario Virgen de la Arrixaca.
Murcia
30120
Spain
Centre Hospitalier Universitaire Vaudois (CHUV)
Vaud (Lausanne)
1011
Switzerland
Faculty of Medicine Siriraj Hospital
Bangkok
10700
Thailand
Hacettepe University Faculty of Medicine
Ankara
06100
Turkey (Türkiye)
Addenbrooke's Hospital
Cambridge
CB2 0QQ
United Kingdom
Imperial College Healthcare NHS Trust
London
W2 INY
United Kingdom
University College London
London
WC1E 6BT
United Kingdom
Derived
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.
FG001
Cohort 1: 20 mg
Participants who received placebo in Study AG348-C-006 and met the eligibility criteria of this extension study were enrolled to receive mitapivat 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, which was followed for a period of 12 weeks (Weeks 13-24) as a fixed dose and then from Week 25 to Week 193, until study withdrawal, or the study was closed.
FG002
Cohort 1: 50 mg
Participants who received placebo in Study AG348-C-006 and met the eligibility criteria of this extension study were enrolled to receive mitapivat 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, which was followed for a period of 12 weeks (Weeks 13-24) as a fixed dose and then from Week 25 to Week 193, until study withdrawal, or the study was closed.
FG003
Cohort 2: 5 mg
Participants who received mitapivat at a dose of 5 mg, BID, in the fixed dose period of Study AG348-C-006 and met the eligibility criteria of this extension study continued to receive the same mitapivat dose up to Week 193 or until study withdrawal, or the study was closed.
FG004
Cohort 2: 20 mg
Participants who received mitapivat at a dose of 20 mg, BID, in the fixed dose period of Study AG348-C-006 and met the eligibility criteria of this extension study continued to receive the same mitapivat dose up to Week 193 or until study withdrawal, or the study was closed.
FG005
Cohort 2: 50 mg
Participants who received mitapivat at a dose of 50 mg, BID, in the fixed dose period of Study AG348-C-006 and met the eligibility criteria of this extension study continued to receive the same mitapivat dose up to Week 193 or until study withdrawal, or the study was closed.
FG006
Cohort 3: 5 mg
Participants who received mitapivat at a dose of 5 mg, BID, in the fixed dose period of Study AG348-C-007 and met the eligibility criteria of this extension study continued to receive the same mitapivat dose up to Week 193 or until study withdrawal, or the study was closed.
FG007
Cohort 3: 20 mg
Participants who received mitapivat at a dose of 20 mg, BID, in the fixed dose period of Study AG348-C-007 and met the eligibility criteria of this extension study continued to receive the same mitapivat dose up to Week 193 or until study withdrawal, or the study was closed.
FG008
Cohort 3: 50 mg
Participants who received mitapivat at a dose of 50 mg, BID, in the fixed dose period of Study AG348-C-007 and met the eligibility criteria of this extension study continued to receive the same mitapivat dose up to Week 193 or until study withdrawal, or the study was closed.
FG0001 subjects
FG0011 subjects
FG00236 subjects
FG0032 subjects
FG0043 subjects
FG00530 subjects
FG0060 subjects
FG0071 subjects
FG00816 subjects
COMPLETED
FG0000 subjects
FG0010 subjects
FG00225 subjects
FG0032 subjects
FG0043 subjects
FG00522 subjects
FG0060 subjects
FG0071 subjects
FG00810 subjects
NOT COMPLETED
FG0001 subjects
FG0011 subjects
FG00211 subjects
FG0030 subjects
FG0040 subjects
FG0058 subjects
FG0060 subjects
FG0070 subjects
FG0086 subjects
Type
Comment
Reasons
Death
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0051 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
Adverse Event
FG0000 subjects
FG0010 subjects
FG0022 subjects
FG0030 subjects
FG004
Withdrawal by Subject
FG0000 subjects
FG0011 subjects
FG0024 subjects
FG0030 subjects
FG004
Physician Decision
FG0001 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Lack of Efficacy
FG0000 subjects
FG0010 subjects
FG0022 subjects
FG0030 subjects
FG004
Approved Drug Available for Indication
FG0000 subjects
FG0010 subjects
FG0021 subjects
FG0030 subjects
FG004
Other un-specified
FG0000 subjects
FG0010 subjects
FG0022 subjects
FG0030 subjects
FG004
Full Analysis Set (FAS) included all participants who received at least 1 dose of study treatment. Due to limited number of participants with optimal dose of 5 mg or 20 mg in antecedent studies AG348-C-006 (NCT03548220) and AG348-C-007 (NCT03559699), it was pre-specified in the statistical analysis plan (SAP) to report data for baseline characteristics by Cohort.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Cohort 1
Participants who received placebo in Study AG348-C-006 and met the eligibility criteria of this extension study were enrolled to receive mitapivat 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 at Week 12, and participants then received that optimized dose for a period of 12 weeks (Weeks 13-24) as a fixed dose and from Week 25 to Week 193, until study withdrawal, or the study was closed.
BG001
Cohort 2
Participants who received mitapivat at a dose of 5 mg, 20 mg, or 50 mg, BID, in the fixed dose period of Study AG348-C-006 and met the eligibility criteria of this extension study continued to receive the same mitapivat dose up to Week 193 or until study withdrawal, or the study was closed.
BG002
Cohort 3
Participants who received mitapivat at a dose of 5 mg, 20 mg, or 50 mg, BID, in the fixed dose period of Study AG348-C-007 and met the eligibility criteria of this extension study continued to receive the same mitapivat dose up to Week 193 or until study withdrawal, or the study was closed.
BG003
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG00038
BG00135
BG00217
BG00390
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Continuous
Mean
Standard Deviation
Years
Title
Denominators
Categories
ParticipantsBG00038
ParticipantsBG00135
ParticipantsBG00217
ParticipantsBG003
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
ParticipantsBG00038
ParticipantsBG00135
ParticipantsBG002
Ethnicity (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
ParticipantsBG00038
ParticipantsBG00135
ParticipantsBG002
Race/Ethnicity, Customized
Count of Participants
Participants
Title
Denominators
Categories
White
ParticipantsBG00038
ParticipantsBG00135
ParticipantsBG002
Femoral Total: T-score
The T-score is the number of standard deviations that bone density is above or below the average. A score of greater than or equal to (≥) -1 indicates normal bone density, a score less than (<) -1 and greater than (>) -2.5 indicates a sign of osteopenia (bone density below normal), and a score less than or equal to (≤) -2.5 indicates a sign of osteoporosis. The baseline is the last assessment before start of study treatment (mitapivat).
Number analyzed is the number of participants that were evaluable for analysis at the baseline.
Mean
Standard Deviation
T-score
Title
Denominators
Categories
ParticipantsBG00038
ParticipantsBG001
Femoral Total: Z-score
The Z-score is a statistical measure to describe whether a value was above or below the standard. A Z-score of 0 is equal to the standard. Lower numbers indicate values lower than the standard and higher numbers indicate values higher than the standard. The baseline is the last assessment before start of study treatment (mitapivat).
Number analyzed is the number of participants that were evaluable for analysis at the baseline.
Mean
Standard Deviation
Z-score
Title
Denominators
Categories
ParticipantsBG00038
ParticipantsBG001
Adjusted Spine: T-Score
The T-score is the number of standard deviations that bone density is above or below the average. A score of ≥ -1 indicates normal bone density; score between < -1 and > -2.5 indicates a sign of osteopenia (bone density below normal), and score of ≤ -2.5 indicates a sign of osteoporosis. The baseline is the last assessment before start of study treatment (mitapivat).
Number analyzed is the number of participants that were evaluable for analysis at the baseline.
Mean
Standard Deviation
T-score
Title
Denominators
Categories
ParticipantsBG00038
ParticipantsBG001
Adjusted Spine: Z-score
The Z-score is a statistical measure to describe whether a value was above or below the standard. A Z-score of 0 is equal to the standard. Lower numbers indicate values lower than the standard and higher numbers indicate values higher than the standard. The baseline is the last assessment before start of study treatment (mitapivat).
Number analyzed is the number of participants that were evaluable for analysis at the baseline.
Mean
Standard Deviation
Z-score
Title
Denominators
Categories
ParticipantsBG00038
ParticipantsBG001
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
All Cohorts: Number of Participants With at Least One Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Related TEAEs and TEAEs With Severity Greater Than or Equal to Grade 3
A clinical adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the study drug. TEAEs are AEs with an initial onset date during the on-treatment period or worsening from baseline and include both serious and non-serious TEAEs. Severity of AEs was evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE; Version 4.03): grade 1: mild; grade 2: moderate; grade 3: severe or medically significant but not immediately life-threatening; grade 4: life threatening or disabling; grade 5: death related to AE.
The safety analysis set included all participants who received at least 1 dose of study treatment. Due to limited number of participants with optimal dose of 5 mg or 20 mg in antecedent studies AG348-C-006 (NCT03548220) and AG348-C-007 (NCT03559699), it was pre-specified in the SAP to report data for this outcome measure (OM) by Cohort.
Posted
Count of Participants
Participants
Up to 197 weeks
ID
Title
Description
OG000
Cohort 1
Participants who received placebo in Study AG348-C-006 and met the eligibility criteria of this extension study were enrolled to receive mitapivat 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 at Week 12, and participants then received that optimized dose for a period of 12 weeks (Weeks 13-24) as a fixed dose and from Week 25 to Week 193, until study withdrawal, or the study was closed.
OG001
Cohort 2
Participants who received mitapivat at a dose of 5 mg, 20 mg, or 50 mg, BID, in the fixed dose period of Study AG348-C-006 and met the eligibility criteria of this extension study continued to receive the same mitapivat dose up to Week 193 or until study withdrawal, or the study was closed.
OG002
Cohort 3
Participants who received mitapivat at a dose of 5 mg, 20 mg, or 50 mg, BID, in the fixed dose period of Study AG348-C-007 and met the eligibility criteria of this extension study continued to receive the same mitapivat dose up to Week 193 or until study withdrawal, or the study was closed.
Units
Counts
Participants
OG00038
OG00135
OG00217
Title
Denominators
Categories
Participants with TEAEs
Title
Measurements
OG00037
OG00133
OG00215
Participants with Serious TEAEs
Primary
All Cohorts: Number of Participants With TEAEs Leading to Dose Reduction, Treatment Interruption and Treatment Discontinuation
A clinical AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the study drug. TEAEs are AEs with an initial onset date during the on-treatment period or worsening from baseline and include both serious and non-serious TEAEs. Number of participants with TEAEs leading to dose reduction, treatment interruption and treatment discontinuation are reported.
The safety analysis set included all participants who received at least 1 dose of study treatment. Due to limited number of participants with optimal dose of 5 mg or 20 mg in antecedent studies AG348-C-006 (NCT03548220) and AG348-C-007 (NCT03559699), it was pre-specified in the SAP to report data for this OM by Cohort.
Posted
Count of Participants
Participants
Up to 197 weeks
ID
Title
Description
OG000
Cohort 1
Participants who received placebo in Study AG348-C-006 and met the eligibility criteria of this extension study were enrolled to receive mitapivat 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 at Week 12, and participants then received that optimized dose for a period of 12 weeks (Weeks 13-24) as a fixed dose and from Week 25 to Week 193, until study withdrawal, or the study was closed.
Primary
All Cohorts: Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters Reported as Grade Greater Than or Equal to (≥)3 TEAEs
Clinical laboratory assessments including hematology, clinical chemistry, triglycerides, urate, coagulation, urinalysis, and liver function tests were performed in the study. Clinically significant treatment-emergent laboratory abnormalities were graded according to the NCI CTCAE; Version 4.03: grade 1: mild; grade 2: moderate; grade 3: severe or medically significant but not immediately life-threatening; grade 4: life threatening or disabling; grade 5: death related to AE. Clinical significance was determined based on the judgment of the Investigator.
The safety analysis set included all participants who received at least 1 dose of study treatment. Due to limited number of participants with optimal dose of 5 mg or 20 mg in antecedent studies AG348-C-006 (NCT03548220) and AG348-C-007 (NCT03559699), it was pre-specified in the SAP to report data for this OM by Cohort.
Posted
Count of Participants
Participants
Up to 197 weeks
ID
Title
Description
OG000
Cohort 1
Participants who received placebo in Study AG348-C-006 and met the eligibility criteria of this extension study were enrolled to receive mitapivat 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 at Week 12, and participants then received that optimized dose for a period of 12 weeks (Weeks 13-24) as a fixed dose and from Week 25 to Week 193, until study withdrawal, or the study was closed.
Primary
All Cohorts: Number of Participants With Clinically Significant Abnormalities in Vital Signs Measurements and Physical Examinations Reported as TEAEs
Vital signs and physical examinations including height, weight, body mass index (BMI), systolic blood pressure, diastolic blood pressure, pulse rate, temperature were assessed. Number of participants who experienced clinically significant abnormalities in vital signs and physical examinations as TEAEs were reported. Clinical significance was determined based on the judgment of the Investigator.
The safety analysis set included all participants who received at least 1 dose of study treatment. Due to limited number of participants with optimal dose of 5 mg or 20 mg in antecedent studies AG348-C-006 (NCT03548220) and AG348-C-007 (NCT03559699), it was pre-specified in the SAP to report data for this OM by Cohort.
Posted
Count of Participants
Participants
Up to 197 weeks
ID
Title
Description
OG000
Cohort 1
Participants who received placebo in Study AG348-C-006 and met the eligibility criteria of this extension study were enrolled to receive mitapivat 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 at Week 12, and participants then received that optimized dose for a period of 12 weeks (Weeks 13-24) as a fixed dose and from Week 25 to Week 193, until study withdrawal, or the study was closed.
Primary
All Cohorts: Number of Participants With Clinically Significant Abnormalities in Bone Mineral Density (BMD)
BMD was measured by dual-energy X-ray absorptiometry (DXA) scans during the study. Number of participants with clinically significant abnormalities were reported. Clinical significance was determined based on the judgment of the Investigator.
The safety analysis set included all participants who received at least 1 dose of study treatment. Due to limited number of participants with optimal dose of 5 mg or 20 mg in antecedent studies AG348-C-006 (NCT03548220) and AG348-C-007 (NCT03559699), it was pre-specified in the SAP to report data for this OM by Cohort.
Posted
Count of Participants
Participants
Up to 192 weeks
ID
Title
Description
OG000
Cohort 1
Participants who received placebo in Study AG348-C-006 and met the eligibility criteria of this extension study were enrolled to receive mitapivat 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 at Week 12, and participants then received that optimized dose for a period of 12 weeks (Weeks 13-24) as a fixed dose and from Week 25 to Week 193, until study withdrawal, or the study was closed.
OG001
Cohort 2
Participants who received mitapivat at a dose of 5 mg, 20 mg, or 50 mg, BID, in the fixed dose period of Study AG348-C-006 and met the eligibility criteria of this extension study continued to receive the same mitapivat dose up to Week 193 or until study withdrawal, or the study was closed.
Primary
All Cohorts: Change From Baseline in Adjusted Spine T-score
T-score of adjusted spine were assessed by DXA scans. The T-score is the number of standard deviations that bone density is above or below the average. A score of ≥ -1 indicates normal bone density; score between < -1 and > -2.5 indicates a sign of osteopenia (bone density below normal), and score of ≤ -2.5 indicates a sign of osteoporosis.
The safety analysis set included all participants who received at least 1 dose of study treatment. Here, overall number of participants analyzed indicates the number of participants who were evaluable for this OM. Due to limited number of participants with optimal dose of 5 mg or 20 mg in antecedent studies AG348-C-006 (NCT03548220) and AG348-C-007 (NCT03559699), it was pre-specified in the SAP to report data for this OM by Cohort.
Posted
Mean
Standard Deviation
T-score
Baseline, Week 192
ID
Title
Description
OG000
Cohort 1
Participants who received placebo in Study AG348-C-006 and met the eligibility criteria of this extension study were enrolled to receive mitapivat 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 at Week 12, and participants then received that optimized dose for a period of 12 weeks (Weeks 13-24) as a fixed dose and from Week 25 to Week 193, until study withdrawal, or the study was closed.
OG001
Primary
All Cohorts: Change From Baseline in Adjusted Spine Z-score
The Z-score is a statistical measure to describe whether a value was above or below the standard. A Z-score of 0 is equal to the standard. Lower numbers indicate values lower than the standard and higher numbers indicate values higher than the standard.
The safety analysis set included all participants who received at least 1 dose of study treatment. Here, overall number of participants analyzed indicates the number of participants who were evaluable for this OM. Due to limited number of participants with optimal dose of 5 mg or 20 mg in antecedent studies AG348-C-006 (NCT03548220) and AG348-C-007 (NCT03559699), it was pre-specified in the SAP to report data for this OM by Cohort.
Posted
Mean
Standard Deviation
Z-score
Baseline, Week 192
ID
Title
Description
OG000
Cohort 1
Participants who received placebo in Study AG348-C-006 and met the eligibility criteria of this extension study were enrolled to receive mitapivat 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 at Week 12, and participants then received that optimized dose for a period of 12 weeks (Weeks 13-24) as a fixed dose and from Week 25 to Week 193, until study withdrawal, or the study was closed.
OG001
Cohort 2
Primary
All Cohorts: Change From Baseline in Femoral Total T-score
T-score of femoral total were assessed by DXA scans. The T-score is the number of standard deviations that bone density is above or below the average. A score of ≥ -1 indicates normal bone density; score between < -1 and > -2.5 indicates a sign of osteopenia (bone density below normal), and score of ≤ -2.5 indicates a sign of osteoporosis.
The safety analysis set included all participants who received at least 1 dose of study treatment. Here, overall number of participants analyzed indicates the number of participants who were evaluable for this OM. Due to limited number of participants with optimal dose of 5 mg or 20 mg in antecedent studies AG348-C-006 (NCT03548220) and AG348-C-007 (NCT03559699), it was pre-specified in the SAP to report data for this OM by Cohort.
Posted
Mean
Standard Deviation
T-score
Baseline, Week 192
ID
Title
Description
OG000
Cohort 1
Participants who received placebo in Study AG348-C-006 and met the eligibility criteria of this extension study were enrolled to receive mitapivat 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 at Week 12, and participants then received that optimized dose for a period of 12 weeks (Weeks 13-24) as a fixed dose and from Week 25 to Week 193, until study withdrawal, or the study was closed.
OG001
Primary
All Cohorts: Change From Baseline in Femoral Total Z-score
The Z-score is a statistical measure to describe whether a value was above or below the standard. A Z-score of 0 is equal to the standard. Lower numbers indicate values lower than the standard and higher numbers indicate values higher than the standard.
The safety analysis set included all participants who received at least 1 dose of study treatment. Here, overall number of participants analyzed indicates the number of participants who were evaluable for this OM. Due to limited number of participants with optimal dose of 5 mg or 20 mg in antecedent studies AG348-C-006 (NCT03548220) and AG348-C-007 (NCT03559699), it was pre-specified in the SAP to report data for this OM by Cohort.
Posted
Mean
Standard Deviation
Z- score
Baseline, Week 192
ID
Title
Description
OG000
Cohort 1
Participants who received placebo in Study AG348-C-006 and met the eligibility criteria of this extension study were enrolled to receive mitapivat 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 at Week 12, and participants then received that optimized dose for a period of 12 weeks (Weeks 13-24) as a fixed dose and from Week 25 to Week 193, until study withdrawal, or the study was closed.
OG001
Cohort 2
Primary
All Cohorts: Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters Reported as TEAEs
The following ECG parameters including RR, PR, heart rate-corrected QT interval using the Fridericia's formula (QRS), QT, and QTc were assessed during the study. Number of Participants with clinically significant abnormalities in ECG parameters as TEAEs were reported. Clinical significance was determined based on the judgment of the Investigator.
The safety analysis set included all participants who received at least 1 dose of study treatment. Due to limited number of participants with optimal dose of 5 mg or 20 mg in antecedent studies AG348-C-006 (NCT03548220) and AG348-C-007 (NCT03559699), it was pre-specified in the SAP to report data for this OM by Cohort.
Posted
Count of Participants
Participants
Up to 197 weeks
ID
Title
Description
OG000
Cohort 1
Participants who received placebo in Study AG348-C-006 and met the eligibility criteria of this extension study were enrolled to receive mitapivat 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 at Week 12, and participants then received that optimized dose for a period of 12 weeks (Weeks 13-24) as a fixed dose and from Week 25 to Week 193, until study withdrawal, or the study was closed.
OG001
Cohort 2
Secondary
Cohort 1: Percentage of Participants Who Achieved a Hemoglobin (Hb) Response
The Hb response was defined as a greater than or equal to (≥)1.5 grams per deciliter (g/dL) (0.93 millimoles per liter [mmol/L]) increase in Hb concentration from baseline that is sustained at 2 or more scheduled assessments, excluding those within 2 months (61 days) of transfusion. The baseline value for cohort 1 participants was the average of all available measurements from the central laboratory within 45 (42+3) days before start of study treatment in study AG348-C-011, excluding values within 61 days after a transfusion, or the baseline value from study AG348-C-006 if no assessment is available.
FAS included all participants who received at least 1 dose of study treatment. Due to limited number of participants with optimal dose of 5 mg or 20 mg in antecedent Study AG348-C-006 (NCT03548220), it was pre-specified in the SAP to report data for this OM by Cohort. As per planned analysis, data for this OM was reported for Cohort 1 only based on FAS.
Posted
Number
percentage of participants
Baseline up to Week 24
ID
Title
Description
OG000
Cohort 1
Participants who received placebo in Study AG348-C-006 and met the eligibility criteria of this extension study were enrolled to receive mitapivat 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 at Week 12, and participants then received that optimized dose for a period of 12 weeks (Weeks 13-24) as a fixed dose and from Week 25 to Week 193, until study withdrawal, or the study was closed.
Secondary
Cohort 1: Average Change From Baseline in Hb Concentration at Weeks 16, 20, and 24
The baseline value for participants was the average of all available measurements from the central laboratory within 45 (42+3) days before start of study treatment in study AG348-C-011, excluding values within 61 days after a transfusion, or the baseline value from study AG348-C-006 if no assessment is available. The mean of average change from baseline in Hb concentration across Weeks 16, 20 and 24 is reported.
FAS included all participants who received at least 1 dose of study treatment. Overall number of participants analyzed indicates number of participants were evaluable for this OM. Due to limited number of participants with optimal dose of 5 mg or 20 mg in antecedent study AG348-C-006 (NCT03548220), it was pre-specified in the SAP to report data for this OM by Cohort. As per planned analysis, data for this OM was reported for Cohort 1 only based on FAS.
Posted
Mean
Standard Deviation
grams per liter
Baseline, Weeks 16, 20, and 24
ID
Title
Description
OG000
Cohort 1
Participants who received placebo in Study AG348-C-006 and met the eligibility criteria of this extension study were enrolled to receive mitapivat 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 at Week 12, and participants then received that optimized dose for a period of 12 weeks (Weeks 13-24) as a fixed dose and from Week 25 to Week 193, until study withdrawal, or the study was closed.
Secondary
Cohort 1: Area Under the Plasma Concentration-Time Curve From Time Zero to 8-hours Post-dose (AUC0-8) of Mitapivat
PK analysis population: all participants who were enrolled & received at least 1 dose of mitapivat with at least 1 nonzero plasma concentration of mitapivat at Week 12 visit. Overall number of participants analyzed: number of participants who received 50 mg BID mitapivat in Cohort 1 and were evaluable for this OM. As per planned analysis, data for this OM was reported by cohort and for Cohort 1 only based on FAS.
Posted
Geometric Mean
Geometric Coefficient of Variation
hour*nanograms per milliliter (hr*ng/mL)
Pre-dose, 0.5, 1, 2, 4, and 8 hours post-dose at Week 12
ID
Title
Description
OG000
Cohort 1
Participants who received placebo in Study AG348-C-006 and met the eligibility criteria of this extension study were enrolled to receive mitapivat 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 at Week 12, and participants then received that optimized dose for a period of 12 weeks (Weeks 13-24) as a fixed dose and from Week 25 to Week 193, until study withdrawal, or the study was closed.
Units
Counts
Participants
Secondary
Cohort 1: Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUC0-last) of Mitapivat
PK analysis population: all participants who were enrolled & received at least 1 dose of mitapivat with at least 1 nonzero plasma concentration of mitapivat at Week 12 visit. Overall number of participants analyzed: number of participants who received 50 mg BID mitapivat in Cohort 1 and were evaluable for this OM. As per planned analysis, data for this OM was reported by cohort and for Cohort 1 only based on FAS.
Posted
Geometric Mean
Geometric Coefficient of Variation
hr*ng/mL
Pre-dose, 0.5, 1, 2, 4, and 8 hours post-dose at Week 12
ID
Title
Description
OG000
Cohort 1
Participants who received placebo in Study AG348-C-006 and met the eligibility criteria of this extension study were enrolled to receive mitapivat 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 at Week 12, and participants then received that optimized dose for a period of 12 weeks (Weeks 13-24) as a fixed dose and from Week 25 to Week 193, until study withdrawal, or the study was closed.
Units
Counts
Participants
Secondary
Cohort 1: Maximum Observed Plasma Concentration (Cmax) of Mitapivat
PK analysis population: all participants who were enrolled & received at least 1 dose of mitapivat with at least 1 nonzero plasma concentration of mitapivat at Week 12 visit. Overall number of participants analyzed: number of participants who received 50 mg BID mitapivat in Cohort 1 and were evaluable for this OM. As per planned analysis, data for this OM was reported by cohort and for Cohort 1 only based on FAS.
Posted
Geometric Mean
Geometric Coefficient of Variation
nanograms/milliliter (ng/mL)
Pre-dose, 0.5, 1, 2, 4, and 8 hours post-dose at Week 12
ID
Title
Description
OG000
Cohort 1
Participants who received placebo in Study AG348-C-006 and met the eligibility criteria of this extension study were enrolled to receive mitapivat 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 at Week 12, and participants then received that optimized dose for a period of 12 weeks (Weeks 13-24) as a fixed dose and from Week 25 to Week 193, until study withdrawal, or the study was closed.
Units
Counts
Participants
Secondary
Cohort 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Mitapivat
PK analysis population: all participants who were enrolled & received at least 1 dose of mitapivat with at least 1 nonzero plasma concentration of mitapivat at Week 12 visit. Overall number of participants analyzed: number of participants who received 50 mg BID mitapivat in Cohort 1 and were evaluable for this OM. As per planned analysis, data for this OM was reported by cohort and for Cohort 1 only based on FAS.
Posted
Median
Full Range
hours
Pre-dose, 0.5, 1, 2, 4, and 8 hours post-dose at Week 12
ID
Title
Description
OG000
Cohort 1
Participants who received placebo in Study AG348-C-006 and met the eligibility criteria of this extension study were enrolled to receive mitapivat 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 at Week 12, and participants then received that optimized dose for a period of 12 weeks (Weeks 13-24) as a fixed dose and from Week 25 to Week 193, until study withdrawal, or the study was closed.
Units
Counts
Participants
Secondary
Cohort 1: Time of Last Quantifiable Concentration (Tlast) of Mitapivat
PK analysis population: all participants who were enrolled & received at least 1 dose of mitapivat with at least 1 nonzero plasma concentration of mitapivat at Week 12 visit. Overall number of participants analyzed: number of participants who received 50 mg BID mitapivat in Cohort 1 and were evaluable for this OM. As per planned analysis, data for this OM was reported by cohort and for Cohort 1 only based on FAS.
Posted
Median
Full Range
hours
Pre-dose, 0.5, 1, 2, 4, and 8 hours post-dose at Week 12
ID
Title
Description
OG000
Cohort 1
Participants who received placebo in Study AG348-C-006 and met the eligibility criteria of this extension study were enrolled to receive mitapivat 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 at Week 12, and participants then received that optimized dose for a period of 12 weeks (Weeks 13-24) as a fixed dose and from Week 25 to Week 193, until study withdrawal, or the study was closed.
Units
Counts
Participants
Secondary
Cohort 1: Plasma Concentration (Ctrough) at the End of a Dosing Interval of Mitapivat
PK analysis population: all participants who were enrolled & received at least 1 dose of mitapivat with at least 1 nonzero plasma concentration of mitapivat at Week 12 visit. Overall number of participants analyzed: number of participants who received 50 mg BID mitapivat in Cohort 1 and were evaluable for this OM. As per planned analysis, data for this OM was reported by cohort and for Cohort 1 only based on FAS.
Posted
Geometric Mean
Geometric Coefficient of Variation
ng/mL
Pre-dose, 0.5, 1, 2, 4, and 8 hours post-dose at Week 12
ID
Title
Description
OG000
Cohort 1
Participants who received placebo in Study AG348-C-006 and met the eligibility criteria of this extension study were enrolled to receive mitapivat 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 at Week 12, and participants then received that optimized dose for a period of 12 weeks (Weeks 13-24) as a fixed dose and from Week 25 to Week 193, until study withdrawal, or the study was closed.
Units
Counts
Participants
Secondary
Cohort 1: Exposure-response (E-R) Relationship Between Safety Parameters and Mitapivat Concentration and Relevant Mitapivat Pharmacokinetic Parameters
After the dose optimization period, the 5 mg and 20 mg doses each had a single participant and the 50 mg dose had 36 participants. The exposure-relationship analysis planned cannot be performed with a single participant in multiple groups.
Posted
Mean
95% Confidence Interval
Percent probability
First dose to up to 24 weeks
ID
Title
Description
OG000
Cohort 1: 5 mg
Participants who received placebo in Study AG348-C-006 and met the eligibility criteria of this extension study were enrolled to receive mitapivat 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, which was followed for a period of 12 weeks (Weeks 13-24) as a fixed dose and then from Week 25 to Week 193, until study withdrawal, or the study was closed.
OG001
Cohort 1: 20 mg
Participants who received placebo in Study AG348-C-006 and met the eligibility criteria of this extension study were enrolled to receive mitapivat 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, which was followed for a period of 12 weeks (Weeks 13-24) as a fixed dose and then from Week 25 to Week 193, until study withdrawal, or the study was closed.
Secondary
Cohorts 1 and 2: Change From Baseline in Hb Concentration
The baseline value for cohort 1 participant was the average of all available measurements from the central laboratory within 45 (42+3) days before start of study treatment in study AG348-C-011, excluding values within 61 days after a transfusion, or the baseline value from study AG348-C-006 if no assessment was available. The baseline value for cohort 2 was from Study AG348-C-006.
FAS included all participants who received at least 1 dose of study treatment. Here, overall number of participants analyzed indicates the number of participants who were evaluable for this OM. Due to limited number of participants with optimal dose of 5 mg or 20 mg in antecedent study AG348-C-006 (NCT03548220), it was pre-specified in the SAP to report data for this OM by Cohort. As per planned analysis, data for this OM was reported for Cohort 1 and 2 only based on FAS.
Posted
Mean
Standard Deviation
grams per liter
Baseline, Week 192
ID
Title
Description
OG000
Cohort 1
Participants who received placebo in Study AG348-C-006 and met the eligibility criteria of this extension study were enrolled to receive mitapivat 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 at Week 12, and participants then received that optimized dose for a period of 12 weeks (Weeks 13-24) as a fixed dose and from Week 25 to Week 193, until study withdrawal, or the study was closed.
Secondary
Cohorts 1 and 2: Change From Baseline in Indirect Bilirubin
The baseline value for cohort 1 participant was the average of all available measurements from the central laboratory within 45 (42+3) days before start of study treatment in study AG348-C-011, excluding values within 61 days after a transfusion, or the baseline value from study AG348-C-006 if no assessment is available. The baseline value for cohort 2 was from Study AG348-C-006.
FAS included all participants who received at least 1 dose of study treatment. Here, overall number of participants analyzed indicates the number of participants who were evaluable for this OM. Due to limited number of participants with optimal dose of 5 mg or 20 mg in antecedent study AG348-C-006 (NCT03548220), it was pre-specified in the SAP to report data for this OM by Cohort. As per planned analysis, data for this OM was reported for Cohort 1 and 2 only based on FAS.
Posted
Mean
Standard Deviation
micromoles per liter (μmol/L)
Baseline, Week 192
ID
Title
Description
OG000
Cohort 1
Participants who received placebo in Study AG348-C-006 and met the eligibility criteria of this extension study were enrolled to receive mitapivat 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 at Week 12, and participants then received that optimized dose for a period of 12 weeks (Weeks 13-24) as a fixed dose and from Week 25 to Week 193, until study withdrawal, or the study was closed.
Secondary
Cohorts 1 and 2: Change From Baseline in Lactate Dehydrogenase (LDH)
The baseline value for cohort 1 participant was the average of all available measurements from the central laboratory within 45 (42+3) days before start of study treatment in study AG348-C-011, excluding values within 61 days after a transfusion, or the baseline value from study AG348-C-006 if no assessment was available. The baseline value for cohort 2 was from Study AG348-C-006.
FAS included all participants who received at least 1 dose of study treatment. Here, overall number of participants analyzed indicates the number of participants who were evaluable for this OM. Due to limited number of participants with optimal dose of 5 mg or 20 mg in antecedent study AG348-C-006 (NCT03548220), it was pre-specified in the SAP to report data for this OM by Cohort. As per planned analysis, data for this OM was reported for Cohort 1 and 2 only based on FAS.
Posted
Mean
Standard Deviation
Units per Liter (U/L)
Baseline, Week 192
ID
Title
Description
OG000
Cohort 1
Participants who received placebo in Study AG348-C-006 and met the eligibility criteria of this extension study were enrolled to receive mitapivat 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 at Week 12, and participants then received that optimized dose for a period of 12 weeks (Weeks 13-24) as a fixed dose and from Week 25 to Week 193, until study withdrawal, or the study was closed.
Secondary
Cohorts 1 and 2: Change From Baseline in Haptoglobin Levels
The baseline value for Cohort 1 participant was the average of all available measurements from the central laboratory within 45 (42+3) days before start of study treatment in study AG348-C-011, excluding values within 61 days after a transfusion, or the baseline value from study AG348-C-006 if no assessment was available. The baseline value for Cohort 2 was from Study AG348-C-006.
FAS included all participants who received at least 1 dose of study treatment. Here, overall number of participants analyzed indicates the number of participants who were evaluable for this OM. Due to limited number of participants with optimal dose of 5 mg or 20 mg in antecedent study AG348-C-006 (NCT03548220), it was pre-specified in the SAP to report data for this OM by Cohort. As per planned analysis, data for this OM was reported for Cohort 1 and 2 only based on FAS.
Posted
Mean
Standard Deviation
grams per liter
Baseline, Week 192
ID
Title
Description
OG000
Cohort 1
Participants who received placebo in Study AG348-C-006 and met the eligibility criteria of this extension study were enrolled to receive mitapivat 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 at Week 12, and participants then received that optimized dose for a period of 12 weeks (Weeks 13-24) as a fixed dose and from Week 25 to Week 193, until study withdrawal, or the study was closed.
Secondary
Cohorts 1 and 2: Change From Baseline in Reticulocytes/Erythrocytes Ratio
The baseline value for Cohort 1 participants was the average of all available measurements from the central laboratory within 45 (42+3) days before start of study treatment in study AG348-C-011, excluding values within 61 days after a transfusion, or the baseline value from study AG348-C-006 if no assessment was available. The baseline value for Cohort 2 was from Study AG348-C-006.
FAS included all participants who received at least 1 dose of study treatment. Here, overall number of participants analyzed indicates the number of participants who were evaluable for this OM. Due to limited number of participants with optimal dose of 5 mg or 20 mg in antecedent study AG348-C-006 (NCT03548220), it was pre-specified in the SAP to report data for this OM by Cohort. As per planned analysis, data for this OM was reported for Cohort 1 and 2 only based on FAS.
Posted
Mean
Standard Deviation
Reticulocytes/Erythrocytes Ratio
Baseline, Week 192
ID
Title
Description
OG000
Cohort 1
Participants who received placebo in Study AG348-C-006 and met the eligibility criteria of this extension study were enrolled to receive mitapivat 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 at Week 12, and participants then received that optimized dose for a period of 12 weeks (Weeks 13-24) as a fixed dose and from Week 25 to Week 193, until study withdrawal, or the study was closed.
Secondary
Cohort 3: Change From Baseline in Number of Transfusion Episodes
Number of transfusions at baseline was determined based on the transfusion data during the 52 weeks before informed consent for Cohort 3. Number of on-study transfusions was based on transfusions collected up to the end of the fixed dose period and standardized to 52 weeks. The change from baseline in number of transfusions was summarized for Cohort 3.
FAS included all participants who received at least 1 dose of study treatment. Due to limited number of participants with optimal dose of 5 mg or 20 mg in antecedent study AG348-C-007 (NCT03559699), it was pre-specified in the SAP to report data for this OM by Cohort. As per planned analysis, data for this OM was reported for Cohort 3 only based on FAS.
Posted
Mean
Standard Deviation
number of transfusion episodes
Baseline, Week 192
ID
Title
Description
OG000
Cohort 3
Participants who received mitapivat at a dose of 5 mg, 20 mg, or 50 mg, BID, in the fixed dose period of Study AG348-C-007 and met the eligibility criteria of this extension study continued to receive the same mitapivat dose up to Week 193 or until study withdrawal, or the study was closed.
Units
Counts
Participants
Secondary
Cohort 3: Change From Baseline in Number of Red Blood Cell (RBC) Units Transfused
Annualized total number of RBC units transfused (units/52-week) during the study, including data up to end of study (EOS), was the total number of RBC units transfused during the entire study*52 / [(date of EOS - date of start of study treatment + 1)/7]. Number of RBC units were determined based on the transfusion data during the 52 weeks before informed consent of the antecedent study for Cohort 3. Number of on-study RBC units was based on transfusion data collected up to the end of the fixed dose period and standardized to 52 weeks.
FAS included all participants who received at least 1 dose of study treatment. Due to limited number of participants with optimal dose of 5 mg or 20 mg in antecedent study AG348-C-007 (NCT03559699), it was pre-specified in the SAP to report data for this OM by Cohort. As per planned analysis, data for this OM was reported for Cohort 3 only based on FAS.
Posted
Mean
Standard Deviation
number of RBC units transfused
Baseline, Week 192
ID
Title
Description
OG000
Cohort 3
Participants who received mitapivat at a dose of 5 mg, 20 mg, or 50 mg, BID, in the fixed dose period of Study AG348-C-007 and met the eligibility criteria of this extension study continued to receive the same mitapivat dose up to Week 193 or until study withdrawal, or the study was closed.
Units
Counts
Secondary
All Cohorts: Change From Baseline in Health-Related Quality of Life (HRQoL) Patient-Reported Outcome (PRO) Scores: Pyruvate Kinase Deficiency Diary (PKDD)
The PKDD is a validated, daily 7-item PRO instrument with a recall period of 24 hours that measures the core signs and symptoms associated with pyruvate kinase deficiency in adults. The symptoms include tiredness, jaundice, bone pain, shortness of breath, and energy level. PKDD daily scores were calculated based on the participant's response to the PKDD questionnaire. Score ranges from 25 to 76, with higher scores indicating more severe symptoms and a higher disease burden. The change from baseline in weekly mean scores was summarized. A negative change from baseline indicates a lower disease burden. Baseline of weekly mean score was defined as average of daily scores collected within 7 days before start of study treatment (mitapivat). For Cohort 1, last measurement before the start of study treatment in AG348-C-011 was used as baseline; if baseline was missing, then baseline value from AG348-C-006 was used. For Cohorts 2 & 3 baseline values from -006 and-007, respectively, were used.
FAS included all participants who received at least 1 dose of study treatment. Here, overall number of participants analyzed indicates the number of participants who were evaluable for this OM. Due to limited number of participants with optimal dose of 5 mg or 20 mg in antecedent studies AG348-C-006 (NCT03548220) and AG348-C-007 (NCT03559699), it was pre-specified in the SAP to report data for this OM by Cohort.
Posted
Mean
Standard Deviation
score on a scale
Baseline, Week 24
ID
Title
Description
OG000
Cohort 1
Participants who received placebo in Study AG348-C-006 and met the eligibility criteria of this extension study were enrolled to receive mitapivat 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 at Week 12, and participants then received that optimized dose for a period of 12 weeks (Weeks 13-24) as a fixed dose and from Week 25 to Week 193, until study withdrawal, or the study was closed.
Secondary
All Cohorts: Change From Baseline in HRQoL PRO Scores: Pyruvate Kinase Deficiency Impact Assessment (PKDIA)
PKDIA is a 12-item PRO measure of common impacts of PK deficiency on activities of daily living. Participants rated how PK deficiency has impacted aspects of daily living in past 7 days, including impacts on relationships & leisure and social, mental, and physical activities. PKDIA score at each visit was based on 8 items that were retained after in-trial psychometric validation and calculated at each visit based on participant's response to PKDIA questionnaire. Score ranges from 30 to 76, with higher scores indicating higher disease burden. Negative change from baseline indicates lower disease burden. Baseline was defined as the last complete assessment (with no missing item in response) before start of study treatment. For Cohort 1, last measurement before start of study treatment in AG348-C-011 was used as baseline; if baseline was missing, then baseline value from AG348-C-006 was used. For Cohorts 2 and 3, the baseline values from 006 and 007, respectively, were used.
FAS included all participants who received at least 1 dose of study treatment. Here, overall number of participants analyzed indicates the number of participants who were evaluable for this OM. Due to limited number of participants with optimal dose of 5 mg or 20 mg in antecedent studies AG348-C-006 (NCT03548220) and AG348-C-007 (NCT03559699), it was pre-specified in the SAP to report data for this OM by Cohort.
Posted
Mean
Standard Deviation
score on a scale
Baseline, Week 24
ID
Title
Description
OG000
Cohort 1
Participants who received placebo in Study AG348-C-006 and met the eligibility criteria of this extension study were enrolled to receive mitapivat 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 at Week 12, and participants then received that optimized dose for a period of 12 weeks (Weeks 13-24) as a fixed dose and from Week 25 to Week 193, until study withdrawal, or the study was closed.
Time Frame
Up to 197 weeks
Description
The safety analysis set included all participants who received at least 1 dose of study treatment.
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
Cohort 1: 5 mg
Participants who received placebo in Study AG348-C-006 and met the eligibility criteria of this extension study were enrolled to receive mitapivat 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, which was followed for a period of 12 weeks (Weeks 13-24) as a fixed dose and then from Week 25 to Week 193, until study withdrawal, or the study was closed.
0
1
1
1
0
1
EG001
Cohort 1: 20 mg
Participants who received placebo in Study AG348-C-006 and met the eligibility criteria of this extension study were enrolled to receive mitapivat 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, which was followed for a period of 12 weeks (Weeks 13-24) as a fixed dose and then from Week 25 to Week 193, until study withdrawal, or the study was closed.
0
1
0
1
1
1
EG002
Cohort 1: 50 mg
Participants who received placebo in Study AG348-C-006 and met the eligibility criteria of this extension study were enrolled to receive mitapivat 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, which was followed for a period of 12 weeks (Weeks 13-24) as a fixed dose and then from Week 25 to Week 193, until study withdrawal, or the study was closed.
0
36
10
36
35
36
EG003
Cohort 2: 5 mg
Participants who received mitapivat at a dose of 5 mg, BID, in the fixed dose period of Study AG348-C-006 and met the eligibility criteria of this extension study continued to receive the same mitapivat dose up to Week 193 or until study withdrawal, or the study was closed.
0
2
0
2
2
2
EG004
Cohort 2: 20 mg
Participants who received mitapivat at a dose of 20 mg, BID, in the fixed dose period of Study AG348-C-006 and met the eligibility criteria of this extension study continued to receive the same mitapivat dose up to Week 193 or until study withdrawal, or the study was closed.
0
3
2
3
2
3
EG005
Cohort 2: 50 mg
Participants who received mitapivat at a dose of 50 mg, BID, in the fixed dose period of Study AG348-C-006 and met the eligibility criteria of this extension study continued to receive the same mitapivat dose up to Week 193 or until study withdrawal, or the study was closed.
1
30
6
30
27
30
EG006
Cohort 3: 5 mg
Participants who received mitapivat at a dose of 5 mg, BID, in the fixed dose period of Study AG348-C-007 and met the eligibility criteria of this extension study continued to receive the same mitapivat dose up to Week 193 or until study withdrawal, or the study was closed.
0
0
0
0
0
0
EG007
Cohort 3: 20 mg
Participants who received mitapivat at a dose of 20 mg, BID, in the fixed dose period of Study AG348-C-007 and met the eligibility criteria of this extension study continued to receive the same mitapivat dose up to Week 193 or until study withdrawal, or the study was closed.
0
1
0
1
1
1
EG008
Cohort 3: 50 mg
Participants who received mitapivat at a dose of 50 mg, BID, in the fixed dose period of Study AG348-C-007 and met the eligibility criteria of this extension study continued to receive the same mitapivat dose up to Week 193 or until study withdrawal, or the study was closed.
0
16
4
16
14
16
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Sepsis
Infections and infestations
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0023 affected36 at risk
EG0030 affected2 at risk
EG0040 affected3 at risk
EG0050 affected30 at risk
EG0060 affected0 at risk
EG0070 affected1 at risk
EG0080 affected16 at risk
Pneumonia
Infections and infestations
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0022 affected36 at risk
EG003
Tonsillitis
Infections and infestations
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0022 affected36 at risk
EG003
Gastroenteritis
Infections and infestations
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0021 affected36 at risk
EG003
Cytomegalovirus infection
Infections and infestations
MedDRA 27.0
Systematic Assessment
EG0001 affected1 at risk
EG0010 affected1 at risk
EG0020 affected36 at risk
EG003
Diverticulitis
Infections and infestations
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0021 affected36 at risk
EG003
Erysipelas
Infections and infestations
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0021 affected36 at risk
EG003
Pharyngitis
Infections and infestations
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0021 affected36 at risk
EG003
Varicella zoster virus infection
Infections and infestations
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0021 affected36 at risk
EG003
COVID-19 pneumonia
Infections and infestations
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0020 affected36 at risk
EG003
Syncope
Nervous system disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0021 affected36 at risk
EG003
Cerebrovascular accident
Nervous system disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0021 affected36 at risk
EG003
Seizure
Nervous system disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0021 affected36 at risk
EG003
Carotid artery aneurysm
Nervous system disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0020 affected36 at risk
EG003
Intracranial aneurysm
Nervous system disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0020 affected36 at risk
EG003
Tibia fracture
Injury, poisoning and procedural complications
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0020 affected36 at risk
EG003
Radius fracture
Injury, poisoning and procedural complications
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0021 affected36 at risk
EG003
Spinal compression fracture
Injury, poisoning and procedural complications
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0021 affected36 at risk
EG003
Accident
Injury, poisoning and procedural complications
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0020 affected36 at risk
EG003
Femur fracture
Injury, poisoning and procedural complications
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0020 affected36 at risk
EG003
Hodgkin's disease
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0021 affected36 at risk
EG003
Hepatocellular carcinoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0020 affected36 at risk
EG003
Metastatic malignant melanoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0020 affected36 at risk
EG003
Meningioma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0020 affected36 at risk
EG003
Haemolysis
Blood and lymphatic system disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0021 affected36 at risk
EG003
Cholecystitis chronic
Hepatobiliary disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0020 affected36 at risk
EG003
Cholelithiasis
Hepatobiliary disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0020 affected36 at risk
EG003
Abdominal pain upper
Gastrointestinal disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0021 affected36 at risk
EG003
Pyrexia
General disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0021 affected36 at risk
EG003
Nephrolithiasis
Renal and urinary disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0021 affected36 at risk
EG003
Vascular stenosis
Vascular disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0021 affected36 at risk
EG003
Asthma
Respiratory, thoracic and mediastinal disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0020 affected36 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
COVID-19
Infections and infestations
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG00212 affected36 at risk
EG0031 affected2 at risk
EG0042 affected3 at risk
EG00513 affected30 at risk
EG0060 affected0 at risk
EG0071 affected1 at risk
EG0085 affected16 at risk
Nasopharyngitis
Infections and infestations
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0026 affected36 at risk
EG003
Upper respiratory tract infection
Infections and infestations
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0029 affected36 at risk
EG003
Sinusitis
Infections and infestations
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0025 affected36 at risk
EG003
Influenza
Infections and infestations
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0022 affected36 at risk
EG003
Urinary tract infection
Infections and infestations
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0022 affected36 at risk
EG003
Gastroenteritis
Infections and infestations
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0022 affected36 at risk
EG003
Suspected COVID-19
Infections and infestations
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0024 affected36 at risk
EG003
Respiratory tract infection
Infections and infestations
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0024 affected36 at risk
EG003
Hordeolum
Infections and infestations
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0023 affected36 at risk
EG003
Oral herpes
Infections and infestations
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0021 affected36 at risk
EG003
Pharyngitis
Infections and infestations
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0023 affected36 at risk
EG003
Respiratory tract infection viral
Infections and infestations
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0022 affected36 at risk
EG003
Viral upper respiratory tract infection
Infections and infestations
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0021 affected36 at risk
EG003
Acarodermatitis
Infections and infestations
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0020 affected36 at risk
EG003
Bronchitis
Infections and infestations
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0022 affected36 at risk
EG003
Rhinitis
Infections and infestations
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0022 affected36 at risk
EG003
Vulvovaginal mycotic infection
Infections and infestations
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0022 affected36 at risk
EG003
Conjunctivitis viral
Infections and infestations
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0020 affected36 at risk
EG003
Ear lobe infection
Infections and infestations
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0020 affected36 at risk
EG003
Enterovirus infection
Infections and infestations
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0020 affected36 at risk
EG003
Escherichia urinary tract infection
Infections and infestations
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0020 affected36 at risk
EG003
Eye infection
Infections and infestations
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0020 affected36 at risk
EG003
Helminthic infection
Infections and infestations
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0020 affected36 at risk
EG003
Implant site infection
Infections and infestations
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0020 affected36 at risk
EG003
Infective tenosynovitis
Infections and infestations
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0020 affected36 at risk
EG003
Pharyngitis streptococcal
Infections and infestations
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0020 affected36 at risk
EG003
Viral infection
Infections and infestations
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0020 affected36 at risk
EG003
Viral sinusitis
Infections and infestations
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0020 affected36 at risk
EG003
Fatigue
General disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0011 affected1 at risk
EG00210 affected36 at risk
EG003
Pyrexia
General disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG00210 affected36 at risk
EG003
Influenza like illness
General disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0024 affected36 at risk
EG003
Oedema peripheral
General disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0023 affected36 at risk
EG003
Asthenia
General disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0022 affected36 at risk
EG003
Injection site pain
General disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0022 affected36 at risk
EG003
Chest pain
General disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0020 affected36 at risk
EG003
Face oedema
General disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0020 affected36 at risk
EG003
Inflammation
General disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0020 affected36 at risk
EG003
Peripheral swelling
General disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0020 affected36 at risk
EG003
Arthralgia
Musculoskeletal and connective tissue disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0029 affected36 at risk
EG003
Back pain
Musculoskeletal and connective tissue disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0025 affected36 at risk
EG003
Pain in extremity
Musculoskeletal and connective tissue disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0025 affected36 at risk
EG003
Osteoporosis
Musculoskeletal and connective tissue disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0024 affected36 at risk
EG003
Myalgia
Musculoskeletal and connective tissue disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0022 affected36 at risk
EG003
Muscle spasms
Musculoskeletal and connective tissue disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0023 affected36 at risk
EG003
Osteopenia
Musculoskeletal and connective tissue disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0020 affected36 at risk
EG003
Joint effusion
Musculoskeletal and connective tissue disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0022 affected36 at risk
EG003
Bone pain
Musculoskeletal and connective tissue disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0021 affected36 at risk
EG003
Joint swelling
Musculoskeletal and connective tissue disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0021 affected36 at risk
EG003
Arthritis
Musculoskeletal and connective tissue disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0022 affected36 at risk
EG003
Musculoskeletal chest pain
Musculoskeletal and connective tissue disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0020 affected36 at risk
EG003
Neck pain
Musculoskeletal and connective tissue disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0022 affected36 at risk
EG003
Osteoarthritis
Musculoskeletal and connective tissue disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0021 affected36 at risk
EG003
Synovial cyst
Musculoskeletal and connective tissue disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0021 affected36 at risk
EG003
Gouty arthritis
Musculoskeletal and connective tissue disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0020 affected36 at risk
EG003
Muscular weakness
Musculoskeletal and connective tissue disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0020 affected36 at risk
EG003
Headache
Nervous system disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0011 affected1 at risk
EG00220 affected36 at risk
EG003
Dizziness
Nervous system disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0023 affected36 at risk
EG003
Anosmia
Nervous system disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0021 affected36 at risk
EG003
Migraine
Nervous system disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0023 affected36 at risk
EG003
Ageusia
Nervous system disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0020 affected36 at risk
EG003
Neuropathy peripheral
Nervous system disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0022 affected36 at risk
EG003
Paraesthesia
Nervous system disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0022 affected36 at risk
EG003
Carotid artery aneurysm
Nervous system disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0020 affected36 at risk
EG003
Cerebrovascular accident
Nervous system disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0020 affected36 at risk
EG003
Intracranial aneurysm
Nervous system disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0020 affected36 at risk
EG003
Diarrhea
Gastrointestinal disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0026 affected36 at risk
EG003
Nausea
Gastrointestinal disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0026 affected36 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0022 affected36 at risk
EG003
Abdominal pain
Gastrointestinal disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0021 affected36 at risk
EG003
Dyspepsia
Gastrointestinal disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0020 affected36 at risk
EG003
Constipation
Gastrointestinal disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0022 affected36 at risk
EG003
Abdominal pain upper
Gastrointestinal disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0023 affected36 at risk
EG003
Gastrooesophageal reflux disease
Gastrointestinal disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0022 affected36 at risk
EG003
Toothache
Gastrointestinal disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0022 affected36 at risk
EG003
Cough
Respiratory, thoracic and mediastinal disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0024 affected36 at risk
EG003
Oropharyngeal pain
Respiratory, thoracic and mediastinal disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0025 affected36 at risk
EG003
Dyspnoea
Respiratory, thoracic and mediastinal disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0025 affected36 at risk
EG003
Asthma
Respiratory, thoracic and mediastinal disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0021 affected36 at risk
EG003
Rhinitis allergic
Respiratory, thoracic and mediastinal disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0023 affected36 at risk
EG003
Rhinorrhoea
Respiratory, thoracic and mediastinal disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0022 affected36 at risk
EG003
Pulmonary mass
Respiratory, thoracic and mediastinal disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0020 affected36 at risk
EG003
Alanine aminotransferase increased
Investigations
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0028 affected36 at risk
EG003
Aspartate aminotransferase increased
Investigations
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0026 affected36 at risk
EG003
Vitamin D decreased
Investigations
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0021 affected36 at risk
EG003
Blood bilirubin increased
Investigations
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0020 affected36 at risk
EG003
High density lipoprotein increased
Investigations
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0020 affected36 at risk
EG003
Weight decreased
Investigations
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0020 affected36 at risk
EG003
Haemoglobin increased
Investigations
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0020 affected36 at risk
EG003
Liver iron concentration increased
Investigations
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0020 affected36 at risk
EG003
Middle insomnia
Psychiatric disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0028 affected36 at risk
EG003
Initial insomnia
Psychiatric disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG00210 affected36 at risk
EG003
Depression
Psychiatric disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0022 affected36 at risk
EG003
Anxiety
Psychiatric disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0022 affected36 at risk
EG003
Panic attack
Psychiatric disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0022 affected36 at risk
EG003
Sleep disorder
Psychiatric disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0021 affected36 at risk
EG003
Stress
Psychiatric disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0020 affected36 at risk
EG003
Vitamin D deficiency
Metabolism and nutrition disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0022 affected36 at risk
EG003
Iron overload
Metabolism and nutrition disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0022 affected36 at risk
EG003
Decreased appetite
Metabolism and nutrition disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0021 affected36 at risk
EG003
Type 2 diabetes mellitus
Metabolism and nutrition disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0022 affected36 at risk
EG003
Fall
Injury, poisoning and procedural complications
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0023 affected36 at risk
EG003
Immunisation reaction
Injury, poisoning and procedural complications
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0023 affected36 at risk
EG003
Contusion
Injury, poisoning and procedural complications
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0023 affected36 at risk
EG003
Bone contusion
Injury, poisoning and procedural complications
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0020 affected36 at risk
EG003
Foot fracture
Injury, poisoning and procedural complications
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0022 affected36 at risk
EG003
Ankle fracture
Injury, poisoning and procedural complications
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0020 affected36 at risk
EG003
Fibula fracture
Injury, poisoning and procedural complications
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0020 affected36 at risk
EG003
Lip injury
Injury, poisoning and procedural complications
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0020 affected36 at risk
EG003
Lipohaemarthrosis
Injury, poisoning and procedural complications
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0020 affected36 at risk
EG003
Tibia fracture
Injury, poisoning and procedural complications
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0020 affected36 at risk
EG003
Anaemia
Blood and lymphatic system disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0025 affected36 at risk
EG003
Haemolysis
Blood and lymphatic system disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0022 affected36 at risk
EG003
Lymphadenopathy
Blood and lymphatic system disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0023 affected36 at risk
EG003
Blood loss anaemia
Blood and lymphatic system disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0020 affected36 at risk
EG003
Thrombocytosis
Blood and lymphatic system disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0020 affected36 at risk
EG003
Jaundice
Hepatobiliary disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0021 affected36 at risk
EG003
Hepatic steatosis
Hepatobiliary disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0020 affected36 at risk
EG003
Hyperbilirubinaemia
Hepatobiliary disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0020 affected36 at risk
EG003
Biliary colic
Hepatobiliary disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0020 affected36 at risk
EG003
Hepatic pain
Hepatobiliary disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0020 affected36 at risk
EG003
Dysuria
Renal and urinary disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0022 affected36 at risk
EG003
Nephrolithiasis
Renal and urinary disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0020 affected36 at risk
EG003
Polyuria
Renal and urinary disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0022 affected36 at risk
EG003
Proteinuria
Renal and urinary disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0020 affected36 at risk
EG003
Renal cyst
Renal and urinary disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0020 affected36 at risk
EG003
Dysmenorrhoea
Reproductive system and breast disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0011 affected1 at risk
EG0021 affected36 at risk
EG003
Menstruation irregular
Reproductive system and breast disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0020 affected36 at risk
EG003
Intermenstrual bleeding
Reproductive system and breast disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0020 affected36 at risk
EG003
Bartholin's cyst
Reproductive system and breast disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0020 affected36 at risk
EG003
Breast cyst
Reproductive system and breast disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0020 affected36 at risk
EG003
Perineal cyst
Reproductive system and breast disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0020 affected36 at risk
EG003
Uterine polyp
Reproductive system and breast disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0020 affected36 at risk
EG003
Rash
Skin and subcutaneous tissue disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0022 affected36 at risk
EG003
Alopecia
Skin and subcutaneous tissue disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0022 affected36 at risk
EG003
Erythema
Skin and subcutaneous tissue disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0020 affected36 at risk
EG003
Hair growth abnormal
Skin and subcutaneous tissue disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0020 affected36 at risk
EG003
Skin hypertrophy
Skin and subcutaneous tissue disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0020 affected36 at risk
EG003
Hot flush
Vascular disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0022 affected36 at risk
EG003
Hypertension
Vascular disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0021 affected36 at risk
EG003
Arteriosclerosis
Vascular disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0021 affected36 at risk
EG003
Haematoma
Vascular disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0020 affected36 at risk
EG003
Ear pain
Ear and labyrinth disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0023 affected36 at risk
EG003
Tinnitus
Ear and labyrinth disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0023 affected36 at risk
EG003
Deafness unilateral
Ear and labyrinth disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0020 affected36 at risk
EG003
Vertigo positional
Ear and labyrinth disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0020 affected36 at risk
EG003
Palpitations
Cardiac disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0021 affected36 at risk
EG003
Sinus bradycardia
Cardiac disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0022 affected36 at risk
EG003
Hypertensive heart disease
Cardiac disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0020 affected36 at risk
EG003
Cataract
Eye disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0020 affected36 at risk
EG003
Vision blurred
Eye disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0022 affected36 at risk
EG003
Lacrimation increased
Eye disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0020 affected36 at risk
EG003
Meibomian gland dysfunction
Eye disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0020 affected36 at risk
EG003
Seasonal allergy
Immune system disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0022 affected36 at risk
EG003
Meningioma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0020 affected36 at risk
EG003
Superficial spreading melanoma stage unspecified
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 27.0
Systematic Assessment
EG0000 affected1 at risk
EG0010 affected1 at risk
EG0020 affected36 at risk
EG003
Certain Agreements
Are all PI(s) employees of the sponsor?
No
Restriction Type
OTHER
Results Disclosure Restriction on PI(s)?
Yes
Other Details
The information obtained from the clinical study will be used towards the development of mitapivat and may be disclosed to regulatory authority(ies), other Investigators, corporate partners, or consultants as required.
Participants who received mitapivat at a dose of 5 mg, 20 mg, or 50 mg, BID, in the fixed dose period of Study AG348-C-006 and met the eligibility criteria of this extension study continued to receive the same mitapivat dose up to Week 193 or until study withdrawal, or the study was closed.
OG002
Cohort 3
Participants who received mitapivat at a dose of 5 mg, 20 mg, or 50 mg, BID, in the fixed dose period of Study AG348-C-007 and met the eligibility criteria of this extension study continued to receive the same mitapivat dose up to Week 193 or until study withdrawal, or the study was closed.
Units
Counts
Participants
OG00038
OG00135
OG00217
Title
Denominators
Categories
Participants with TEAEs Leading to Dose Reduction
Title
Measurements
OG0002
OG0012
OG0021
Participants with TEAEs Leading to Interruption
Title
Measurements
OG0003
OG0014
OG0020
Participants with TEAEs Leading to Discontinuation
Title
Measurements
OG0002
OG0011
OG0020
OG001
Cohort 2
Participants who received mitapivat at a dose of 5 mg, 20 mg, or 50 mg, BID, in the fixed dose period of Study AG348-C-006 and met the eligibility criteria of this extension study continued to receive the same mitapivat dose up to Week 193 or until study withdrawal, or the study was closed.
OG002
Cohort 3
Participants who received mitapivat at a dose of 5 mg, 20 mg, or 50 mg, BID, in the fixed dose period of Study AG348-C-007 and met the eligibility criteria of this extension study continued to receive the same mitapivat dose up to Week 193 or until study withdrawal, or the study was closed.
Units
Counts
Participants
OG00038
OG00135
OG00217
Title
Denominators
Categories
Anaemia
Title
Measurements
OG0003
OG0011
OG0020
Haemolysis
Title
Measurements
OG0001
OG0012
OG0020
Alanine aminotransferase increased
Title
Measurements
OG0000
OG0010
OG0021
Aspartate aminotransferase increased
Title
Measurements
OG0002
OG0011
OG0021
Blood bilirubin increased
Title
Measurements
OG0000
OG0010
OG0021
Blood triglycerides increased
Title
Measurements
OG0001
OG0010
OG0020
Hypertriglyceridaemia
Title
Measurements
OG0001
OG0010
OG0020
OG001
Cohort 2
Participants who received mitapivat at a dose of 5 mg, 20 mg, or 50 mg, BID, in the fixed dose period of Study AG348-C-006 and met the eligibility criteria of this extension study continued to receive the same mitapivat dose up to Week 193 or until study withdrawal, or the study was closed.
OG002
Cohort 3
Participants who received mitapivat at a dose of 5 mg, 20 mg, or 50 mg, BID, in the fixed dose period of Study AG348-C-007 and met the eligibility criteria of this extension study continued to receive the same mitapivat dose up to Week 193 or until study withdrawal, or the study was closed.
Units
Counts
Participants
OG00038
OG00135
OG00217
Title
Denominators
Categories
Weight decreased
Title
Measurements
OG0000
OG0011
OG0021
Hot flush
Title
Measurements
OG0002
OG0010
OG0022
Hypotension
Title
Measurements
OG0001
OG0010
OG0020
Hypertension
Title
Measurements
OG0001
OG0012
OG0020
OG002
Cohort 3
Participants who received mitapivat at a dose of 5 mg, 20 mg, or 50 mg, BID, in the fixed dose period of Study AG348-C-007 and met the eligibility criteria of this extension study continued to receive the same mitapivat dose up to Week 193 or until study withdrawal, or the study was closed.
Units
Counts
Participants
OG00038
OG00135
OG00217
Title
Denominators
Categories
Title
Measurements
OG0000
OG0011
OG0020
Cohort 2
Participants who received mitapivat at a dose of 5 mg, 20 mg, or 50 mg, BID, in the fixed dose period of Study AG348-C-006 and met the eligibility criteria of this extension study continued to receive the same mitapivat dose up to Week 193 or until study withdrawal, or the study was closed.
OG002
Cohort 3
Participants who received mitapivat at a dose of 5 mg, 20 mg, or 50 mg, BID, in the fixed dose period of Study AG348-C-007 and met the eligibility criteria of this extension study continued to receive the same mitapivat dose up to Week 193 or until study withdrawal, or the study was closed.
Units
Counts
Participants
OG00024
OG00120
OG0028
Title
Denominators
Categories
Title
Measurements
OG0000.046± 0.4874
OG0010.234± 0.4383
OG0020.416± 1.1090
Participants who received mitapivat at a dose of 5 mg, 20 mg, or 50 mg, BID, in the fixed dose period of Study AG348-C-006 and met the eligibility criteria of this extension study continued to receive the same mitapivat dose up to Week 193 or until study withdrawal, or the study was closed.
OG002
Cohort 3
Participants who received mitapivat at a dose of 5 mg, 20 mg, or 50 mg, BID, in the fixed dose period of Study AG348-C-007 and met the eligibility criteria of this extension study continued to receive the same mitapivat dose up to Week 193 or until study withdrawal, or the study was closed.
Units
Counts
Participants
OG00024
OG00120
OG0028
Title
Denominators
Categories
Title
Measurements
OG0000.152± 0.4585
OG0010.332± 0.4002
OG0020.530± 1.2409
Cohort 2
Participants who received mitapivat at a dose of 5 mg, 20 mg, or 50 mg, BID, in the fixed dose period of Study AG348-C-006 and met the eligibility criteria of this extension study continued to receive the same mitapivat dose up to Week 193 or until study withdrawal, or the study was closed.
OG002
Cohort 3
Participants who received mitapivat at a dose of 5 mg, 20 mg, or 50 mg, BID, in the fixed dose period of Study AG348-C-007 and met the eligibility criteria of this extension study continued to receive the same mitapivat dose up to Week 193 or until study withdrawal, or the study was closed.
Units
Counts
Participants
OG00024
OG00120
OG0028
Title
Denominators
Categories
Title
Measurements
OG000-0.020± 0.2612
OG0010.047± 0.3893
OG0020.114± 0.5050
Participants who received mitapivat at a dose of 5 mg, 20 mg, or 50 mg, BID, in the fixed dose period of Study AG348-C-006 and met the eligibility criteria of this extension study continued to receive the same mitapivat dose up to Week 193 or until study withdrawal, or the study was closed.
OG002
Cohort 3
Participants who received mitapivat at a dose of 5 mg, 20 mg, or 50 mg, BID, in the fixed dose period of Study AG348-C-007 and met the eligibility criteria of this extension study continued to receive the same mitapivat dose up to Week 193 or until study withdrawal, or the study was closed.
Units
Counts
Participants
OG00024
OG00120
OG0028
Title
Denominators
Categories
Title
Measurements
OG0000.054± 0.2468
OG0010.126± 0.3631
OG0020.214± 0.5099
Participants who received mitapivat at a dose of 5 mg, 20 mg, or 50 mg, BID, in the fixed dose period of Study AG348-C-006 and met the eligibility criteria of this extension study continued to receive the same mitapivat dose up to Week 193 or until study withdrawal, or the study was closed.
OG002
Cohort 3
Participants who received mitapivat at a dose of 5 mg, 20 mg, or 50 mg, BID, in the fixed dose period of Study AG348-C-007 and met the eligibility criteria of this extension study continued to receive the same mitapivat dose up to Week 193 or until study withdrawal, or the study was closed.
Units
Counts
Participants
OG00038
OG00135
OG00217
Title
Denominators
Categories
Title
Measurements
OG0000
OG0011
OG0020
Units
Counts
Participants
OG00038
Title
Denominators
Categories
Title
Measurements
OG00039.5
Units
Counts
Participants
OG00036
Title
Denominators
Categories
Title
Measurements
OG00016.45± 15.634
OG00023
Title
Denominators
Categories
Title
Measurements
OG0003016± 27.5
OG00028
Title
Denominators
Categories
Title
Measurements
OG0002990± 26.3
OG00030
Title
Denominators
Categories
Title
Measurements
OG0001018± 22.5
OG00030
Title
Denominators
Categories
Title
Measurements
OG0001.00(0.45 to 4.3)
OG00028
Title
Denominators
Categories
Title
Measurements
OG0007.61(3.57 to 8.53)
OG00028
Title
Denominators
Categories
Title
Measurements
OG00062.8± 72.7
OG002
Cohort 1: 50 mg
Participants who received placebo in Study AG348-C-006 and met the eligibility criteria of this extension study were enrolled to receive mitapivat 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, which was followed for a period of 12 weeks (Weeks 13-24) as a fixed dose and then from Week 25 to Week 193, until study withdrawal, or the study was closed.
Units
Counts
Participants
OG0001
OG0011
OG00236
Title
Denominators
Categories
Title
Measurements
OG000NA(NA to NA)After the dose optimization period, the 5 mg and 20 mg doses each had a single participant and the 50 mg dose had 36 participants. The exposure-relationship analysis planned cannot be performed with a single participant in multiple groups.
OG001NA(NA to NA)After the dose optimization period, the 5 mg and 20 mg doses each had a single participant and the 50 mg dose had 36 participants. The exposure-relationship analysis planned cannot be performed with a single participant in multiple groups.
OG002NA(NA to NA)After the dose optimization period, the 5 mg and 20 mg doses each had a single participant and the 50 mg dose had 36 participants. The exposure-relationship analysis planned cannot be performed with a single participant in multiple groups.
OG001
Cohort 2
Participants who received mitapivat at a dose of 5 mg, 20 mg, or 50 mg, BID, in the fixed dose period of Study AG348-C-006 and met the eligibility criteria of this extension study continued to receive the same mitapivat dose up to Week 193 or until study withdrawal, or the study was closed.
Units
Counts
Participants
OG00022
OG00123
Title
Denominators
Categories
Title
Measurements
OG00022.39± 21.211
OG00121.32± 20.721
OG001
Cohort 2
Participants who received mitapivat at a dose of 5 mg, 20 mg, or 50 mg, BID, in the fixed dose period of Study AG348-C-006 and met the eligibility criteria of this extension study continued to receive the same mitapivat dose up to Week 193 or until study withdrawal, or the study was closed.
Units
Counts
Participants
OG00022
OG00121
Title
Denominators
Categories
Title
Measurements
OG000-57.50± 54.542
OG001-36.73± 35.511
OG001
Cohort 2
Participants who received mitapivat at a dose of 5 mg, 20 mg, or 50 mg, BID, in the fixed dose period of Study AG348-C-006 and met the eligibility criteria of this extension study continued to receive the same mitapivat dose up to Week 193 or until study withdrawal, or the study was closed.
Units
Counts
Participants
OG00024
OG00122
Title
Denominators
Categories
Title
Measurements
OG000-46.10± 75.310
OG001-130.80± 275.424
OG001
Cohort 2
Participants who received mitapivat at a dose of 5 mg, 20 mg, or 50 mg, BID, in the fixed dose period of Study AG348-C-006 and met the eligibility criteria of this extension study continued to receive the same mitapivat dose up to Week 193 or until study withdrawal, or the study was closed.
Units
Counts
Participants
OG00024
OG00125
Title
Denominators
Categories
Title
Measurements
OG0000.254± 0.4340
OG0010.250± 0.4689
OG001
Cohort 2
Participants who received mitapivat at a dose of 5 mg, 20 mg, or 50 mg, BID, in the fixed dose period of Study AG348-C-006 and met the eligibility criteria of this extension study continued to receive the same mitapivat dose up to Week 193 or until study withdrawal, or the study was closed.
Units
Counts
Participants
OG00022
OG00120
Title
Denominators
Categories
Title
Measurements
OG000-0.1696± 0.16243
OG001-0.1565± 0.14631
OG00017
Title
Denominators
Categories
Title
Measurements
OG0004.14± 5.487
Participants
OG00017
Title
Denominators
Categories
Title
Measurements
OG0007.25± 7.915
OG001
Cohort 2
Participants who received mitapivat at a dose of 5 mg, 20 mg, or 50 mg, BID, in the fixed dose period of Study AG348-C-006 and met the eligibility criteria of this extension study continued to receive the same mitapivat dose up to Week 193 or until study withdrawal, or the study was closed.
OG002
Cohort 3
Participants who received mitapivat at a dose of 5 mg, 20 mg, or 50 mg, BID, in the fixed dose period of Study AG348-C-007 and met the eligibility criteria of this extension study continued to receive the same mitapivat dose up to Week 193 or until study withdrawal, or the study was closed.
Units
Counts
Participants
OG00027
OG00124
OG00210
Title
Denominators
Categories
Title
Measurements
OG000-3.75± 5.805
OG001-6.09± 7.617
OG002-5.04± 12.273
OG001
Cohort 2
Participants who received mitapivat at a dose of 5 mg, 20 mg, or 50 mg, BID, in the fixed dose period of Study AG348-C-006 and met the eligibility criteria of this extension study continued to receive the same mitapivat dose up to Week 193 or until study withdrawal, or the study was closed.
OG002
Cohort 3
Participants who received mitapivat at a dose of 5 mg, 20 mg, or 50 mg, BID, in the fixed dose period of Study AG348-C-007 and met the eligibility criteria of this extension study continued to receive the same mitapivat dose up to Week 193 or until study withdrawal, or the study was closed.