A Phase 1, Randomized, Four-Period, Crossover Food-Effect Study With Mitapivat Sulfate In Healthy Subjects
Overview
- Phase
- Phase 1
- Intervention
- Placebo for Treatment A
- Conditions
- Healthy Volunteers
- Sponsor
- Agios Pharmaceuticals, Inc.
- Enrollment
- 32
- Locations
- 1
- Primary Endpoint
- AUC From Time 0 Extrapolated to Infinity (AUC0-Inf) for Mitapivat Under Fasted and High-Fat Meal Conditions
- Status
- Completed
- Last Updated
- 5 years ago
Overview
Brief Summary
This is a Phase 1, randomized, single-dose, double-blinded, 4-period, crossover study to evaluate the pharmacokinetics, safety, and tolerability of mitapivat in healthy adult participants under fasted and fed (high-fat meal) conditions. Secondary objectives include evaluating the effect of mitapivat on electrocardiogram (ECG) parameters, including concentration-QT interval corrected for heart rate (C-QTc) analysis under fasted conditions. The study will include a 28-day screening period, four 7-day treatment periods. Participants will receive a follow-up telephone call within 28 (±1) days after the last dose of study drug.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Participant is male or female 18 to 55 years of age, inclusive;
- •If female, is not currently pregnant or breastfeeding OR is of non-childbearing potential, defined as either:
- •Being clinically infertile as the result of surgical sterilization, confirmed postmenopausal status, or another documented medical condition (eg, was born without a uterus) OR
- •Agreeing to either abstain from sexual intercourse with a male partner OR agrees to use a highly effective form of contraception, beginning at the time of screening and continuing throughout the study and for 28 days after dosing. The following are considered highly effective forms of contraception: hormonal oral contraceptives, injectables, and patches; intrauterine devices; double-barrier methods (synthetic condom, diaphragm, or cervical cap used with spermicidal foam, cream, or gel); and male partner sterilization;
- •If male, agrees to abstain from sexual intercourse with a female partner OR agrees to use a highly effective form of contraception, beginning at the time of screening and continuing throughout the study and for 90 days after dosing, AND to refrain from donating sperm for the duration of the study and for 90 days after dosing;
- •Participant has a body mass index 18 to 32 kilograms per square meter (kg/m\^2), inclusive, at screening;
- •Participant is considered by the investigator to be in good general health as determined by medical history, clinical laboratory test results, vital sign measurements, 12-lead ECG results, and physical examination findings at screening;
- •Participant has no clinically significant history or presence of ECG findings as judged by the investigator at screening and check-in, including each criterion as follows:
- •Normal sinus rhythm (heart rate \[HR\] between 45 beats per minute \[bpm\] and 100 bpm inclusive);
- •QT interval corrected for HR using Fridericia's formula (QTcF) ≤450 milliseconds (msec);
Exclusion Criteria
- •Participant has any medical or surgical condition that, in the opinion of the investigator, could affect study drug absorption, distribution, metabolism, or excretion;
- •Participant has undergone any major surgical procedure within the 3 months prior to screening;
- •Participant has a history of any primary malignancy (including any melanoma or suspicious undiagnosed skin lesions), with the exception of in situ basal cell or squamous cell carcinomas of the skin, cervical carcinoma in situ, or other malignancies that have been curatively treated and for which the participant has displayed no evidence of disease within the 5 years prior to screening;
- •Participant has glucose-6-phosphate-dehydrogenase deficiency;
- •Participant has a known history or presence of liver disease.
- •Participant has a positive test result for hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCVAb), or human immunodeficiency virus (HIV) types 1 or 2 antibodies at screening;
- •Participant has liver function tests including alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, and total bilirubin that are greater than the upper limit of normal at screening or check-in (results may be repeated once);
- •Participant has platelet count or hemoglobin and hematocrit values that are below the lower limit of normal at screening or check-in (results may be repeated once);
- •Participant has a positive test result for drugs of abuse, alcohol, or cotinine (indicating active current smoking) at screening or before the first dose of study drug or throughout the study.
- •Participant has used any prescription (excluding hormonal birth control) medications within 30 days (or 5 half-lives, whichever is longer) before the first dose of study drug or throughout the study;
Arms & Interventions
Treatment A
Participants will receive a single oral dose of mitapivat-matching placebo under fasted conditions on Day 1 of each of 4 periods.
Intervention: Placebo for Treatment A
Treatment B
Participants will receive a single oral dose of mitapivat 100 milligrams (mg) and placebo under fasted conditions on Day 1 of each of 4 periods.
Intervention: Mitapivat 100 mg
Treatment B
Participants will receive a single oral dose of mitapivat 100 milligrams (mg) and placebo under fasted conditions on Day 1 of each of 4 periods.
Intervention: Placebo for Treatment B
Treatment C
Participants will receive a single oral dose of mitapivat 100 mg and placebo under high-fat meal conditions on Day 1 of each of 4 periods.
Intervention: Mitapivat 100 mg
Treatment C
Participants will receive a single oral dose of mitapivat 100 mg and placebo under high-fat meal conditions on Day 1 of each of 4 periods.
Intervention: Placebo for Treatment C
Treatment D
Participants will receive a single oral dose of mitapivat 300 mg under fasted conditions on Day 1 of each of 4 periods.
Intervention: Mitapivat 300 mg
Outcomes
Primary Outcomes
AUC From Time 0 Extrapolated to Infinity (AUC0-Inf) for Mitapivat Under Fasted and High-Fat Meal Conditions
Time Frame: Predose and at various timepoints through 120 hours postdose within each 7-day period
Maximum Observed Plasma Concentration (Cmax) for Mitapivat Under Fasted and High-Fat Meal Conditions
Time Frame: Predose and at various timepoints through 120 hours postdose within each 7-day period
Relative Bioavailability (Frel; AUC0-Inf [fed]/AUC0-Inf [fasted]) for Fed Treatment Following Administration of Mitapivat 100-mg Dose
Time Frame: Predose and at various timepoints through 120 hours postdose within each 7-day period
Area Under the Plasma Concentration Versus Time Curve (AUC) From Time 0 to the Last Quantifiable Concentration (AUC0-T) for Mitapivat Under Fasted and High-Fat Meal Conditions
Time Frame: Predose and at various timepoints through 120 hours postdose within each 7-day period
Apparent Oral Clearance (CL/F) for Mitapivat Under Fasted and High-Fat Meal Conditions
Time Frame: Predose and at various timepoints through 120 hours postdose within each 7-day period
Time to Reach Maximum Observed Plasma Concentration (Tmax) for Mitapivat Under Fasted and High-Fat Meal Conditions
Time Frame: Predose and at various timepoints through 120 hours postdose within each 7-day period
Apparent Terminal Elimination Half-Life (T1/2) for Mitapivat Under Fasted and High-Fat Meal Conditions
Time Frame: Predose and at various timepoints through 120 hours postdose within each 7-day period
Apparent Terminal Elimination Rate Constant (Λz) for Mitapivat Under Fasted and High-Fat Meal Conditions
Time Frame: Predose and at various timepoints through 120 hours postdose within each 7-day period
Apparent Volume of Distribution (Vd/F) for Mitapivat Under Fasted and High-Fat Meal Conditions
Time Frame: Predose and at various timepoints through 120 hours postdose within each 7-day period
Secondary Outcomes
- Percentage of Participants With Abnormalities in 12-lead Electrocardiogram (ECG) Results(Up to approximately 8 weeks)
- Percentage of Participants With Adverse Events (AEs)(Up to approximately 8 weeks)
- Percentage of Participants With Abnormalities in Vital Sign Measurements(Up to approximately 8 weeks)
- Percentage of Participants with Abnormalities in Clinical Laboratory Findings(Up to approximately 8 weeks)
- Percentage of Participants With Abnormalities in Physical Examination Findings(Up to approximately 8 weeks)