A Study to Assess the Relative Bioavailability and Effect of Food on the Coated Granule Formulation of Mitapivat in Healthy Participants
Phase 1
Completed
- Conditions
- Healthy Volunteers
- Interventions
- Registration Number
- NCT04565678
- Lead Sponsor
- Agios Pharmaceuticals, Inc.
- Brief Summary
The primary purpose of this study is to assess the relative bioavailability of the mitapivat coated granule formulation compared to the tablet formulation following a single oral dose of mitapivat under fasted conditions in healthy adult participants.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 32
Inclusion Criteria
- Body mass index between 18.0 and 32.0 kilograms per square meter (kg/m^2), inclusive;
- In good health, determined by no clinically significant findings from medical history, physical examination, 12-lead electrocardiogram (ECG), vital signs measurements, and clinical laboratory evaluations;
- Females will not be pregnant or lactating, and females of childbearing potential and males will agree to use contraception;
- Participant has no clinically significant history or presence of ECG findings as judged by the Investigator at Screening and Check-in.
Exclusion Criteria
- Significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, respiratory, endocrine, or psychiatric disorder, as determined by the Investigator;
- History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, including the 2 soft foods administered in this study, or other substance, unless approved by the Investigator;
- History of stomach or intestinal surgery or resection including cholecystectomy that would potentially alter absorption and/or excretion of orally administered drugs (uncomplicated appendectomy and hernia repair will be allowed);
- History of any malignancy with the exception of non-melanomatous skin cancer in situ, cervical carcinoma in situ, or breast carcinoma in situ;
- Participant has liver function tests including alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase, and total bilirubin that are greater than the upper limit of normal at Screening or Check-in;
- Participant has platelet count or hemoglobin and hematocrit values that are below the lower limit of normal at Screening or Check-in;
- Confirmed (eg, original value and 2 consecutive repeat measurements) systolic blood pressure >150 or <90 millimeters of mercury (mmHg), diastolic blood pressure >90 or <50 mmHg, and pulse rate >100 or <45 beats per minute (bpm);
- Confirmed QT interval corrected for heart rate using Fridericia's method (QTcF) >450 milliseconds (msec) (male participants) or >470 msec (female participants);
- History of active alcoholism or drug/chemical abuse within 2 years prior to Check-in;
- Alcohol consumption of >21 units per week for males and >14 units for females;
- Positive urine drug screen at Screening or positive alcohol breath test result or positive urine drug screen at Check-in;
- Positive hepatitis panel and/or positive human immunodeficiency virus test;
- Participants with an active infection requiring systemic antimicrobial therapy, or with an active infection deemed clinically significant by the Investigator during Screening;
- Participation in a clinical study involving administration of an investigational drug (new chemical entity) in the past 30 days or 5 half-lives prior to dosing (whichever is longer);
- Participant has used any over-the-counter medications, including herbal or nutritional supplements, within 28 days (or 5 half-lives, whichever is longer) before the first dose of study drug until after the Follow up phone call;
- Participant has used any prescription (excluding hormone replacement therapy and hormonal birth control) medications within 30 days (or 5 half-lives, whichever is longer) before the first dose of study drug until after the Follow up phone call;
- Use of tobacco- or nicotine-containing products including cigarettes, snuff, nicotine patch, nicotine chewing gum, vaporizers, or inhalers, within 6 months prior to Screening until after the Follow up phone call, or positive cotinine at Screening or Check-in;
- Participant must refrain from marijuana or cannabinol-containing products for 7 days before Screening until after the Follow up phone call;
- Ingestion of poppy seed within 7 days prior to Check-in until after the Follow up phone call;
- Participant has consumed grapefruit or grapefruit juice, Seville orange, or Seville orange containing products (eg, marmalade) within 7 days before the first dose of study drug until after the Follow up phone call;
- Participant has consumed caffeine- or xanthine-containing products within 24 hours prior to first dose of study drug until after the Follow up phone call;
- Participant has consumed vegetables from the mustard green family (eg, kale, broccoli, watercress, collard greens, kohlrabi, Brussels sprouts, and mustard), or charbroiled meats for 7 days prior to first dose of study drug until after the Follow-up phone call;
- Participant is involved in strenuous activity or contact sports from 7 days before Check-in until after the Follow-up phone call;
- Receipt of blood products within 2 months prior to Check-in;
- Participant has donated blood or blood products >450 milliliters (mL) within 30 days before the first dose of study drug;
- Participant has a poor peripheral venous access;
- Have previously completed or withdrawn from this study or any other study investigating mitapivat sulfate, and have previously received the mitapivat sulfate;
- Participant has a history of allergy to sulfonamides (eg, co-trimoxazole antibiotic, silver sulfadiazine topical antibiotic for burn wounds) that has been characterized by acute hemolytic anemia, drug-induced liver injury, anaphylaxis, rash of erythema multiforme type, or Stevens-Johnson syndrome.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Treatment Sequence 4: DCBA Mitapivat tablets Participants will receive Treatment D (mitapivat coated granules, with a chocolate pudding, orally once on Day 1 of Period 1) followed by Treatment C (mitapivat coated granules, with a strawberry yogurt, orally once on Day 1 of Period 2) followed by Treatment B (mitapivat coated granules, orally, under fasted conditions once on Day 1 of Period 3) followed by Treatment A (mitapivat tablet, orally, under fasted conditions once on Day 1 of Period 4). Each Treatment Period will be separated by a Washout Period of 7 days. Treatment Sequence 2: BDAC Mitapivat coated granules Participants will receive Treatment B (mitapivat coated granules, orally, under fasted conditions once on Day 1 of Period 1) followed by Treatment D (mitapivat coated granules, with a chocolate pudding, orally once on Day 1 of Period 2) followed by Treatment A (mitapivat tablet, orally, under fasted conditions once on Day 1 of Period 3) followed by Treatment C (mitapivat coated granules, with a strawberry yogurt, orally once on Day 1 of Period 4). Each Treatment Period will be separated by a Washout Period of 7 days. Treatment Sequence 1: ABCD Mitapivat tablets Participants will receive Treatment A (mitapivat tablet, orally, under fasted conditions once on Day 1 of Period 1) followed by Treatment B (mitapivat coated granules, orally, under fasted conditions once on Day 1 of Period 2) followed by Treatment C (mitapivat coated granules, with a strawberry yogurt, orally once on Day 1 of Period 3) followed by Treatment D (mitapivat coated granules, with a chocolate pudding, orally once on Day 1 of Period 4). Each Treatment Period will be separated by a Washout Period of 7 days. Treatment Sequence 2: BDAC Mitapivat tablets Participants will receive Treatment B (mitapivat coated granules, orally, under fasted conditions once on Day 1 of Period 1) followed by Treatment D (mitapivat coated granules, with a chocolate pudding, orally once on Day 1 of Period 2) followed by Treatment A (mitapivat tablet, orally, under fasted conditions once on Day 1 of Period 3) followed by Treatment C (mitapivat coated granules, with a strawberry yogurt, orally once on Day 1 of Period 4). Each Treatment Period will be separated by a Washout Period of 7 days. Treatment Sequence 3: CADB Mitapivat coated granules Participants will receive Treatment C (mitapivat coated granules, with a strawberry yogurt, orally once on Day 1 of Period 1) followed by Treatment A (mitapivat tablet, orally, under fasted conditions once on Day 1 of Period 2) followed by Treatment D (mitapivat coated granules, with a chocolate pudding, orally once on Day 1 of Period 3) followed by Treatment B (mitapivat coated granules, orally, under fasted conditions once on Day 1 of Period 4). Each Treatment Period will be separated by a Washout Period of 7 days. Treatment Sequence 1: ABCD Mitapivat coated granules Participants will receive Treatment A (mitapivat tablet, orally, under fasted conditions once on Day 1 of Period 1) followed by Treatment B (mitapivat coated granules, orally, under fasted conditions once on Day 1 of Period 2) followed by Treatment C (mitapivat coated granules, with a strawberry yogurt, orally once on Day 1 of Period 3) followed by Treatment D (mitapivat coated granules, with a chocolate pudding, orally once on Day 1 of Period 4). Each Treatment Period will be separated by a Washout Period of 7 days. Treatment Sequence 3: CADB Mitapivat tablets Participants will receive Treatment C (mitapivat coated granules, with a strawberry yogurt, orally once on Day 1 of Period 1) followed by Treatment A (mitapivat tablet, orally, under fasted conditions once on Day 1 of Period 2) followed by Treatment D (mitapivat coated granules, with a chocolate pudding, orally once on Day 1 of Period 3) followed by Treatment B (mitapivat coated granules, orally, under fasted conditions once on Day 1 of Period 4). Each Treatment Period will be separated by a Washout Period of 7 days. Treatment Sequence 4: DCBA Mitapivat coated granules Participants will receive Treatment D (mitapivat coated granules, with a chocolate pudding, orally once on Day 1 of Period 1) followed by Treatment C (mitapivat coated granules, with a strawberry yogurt, orally once on Day 1 of Period 2) followed by Treatment B (mitapivat coated granules, orally, under fasted conditions once on Day 1 of Period 3) followed by Treatment A (mitapivat tablet, orally, under fasted conditions once on Day 1 of Period 4). Each Treatment Period will be separated by a Washout Period of 7 days.
- Primary Outcome Measures
Name Time Method Time to Reach Maximum Observed Concentration (Tmax) of Mitapivat Under Fasted Conditions Pre-dose and multiple time points post-dose (up to 72 hours) Maximum Observed Concentration (Cmax) of Mitapivat Under Fasted Conditions Pre-dose and multiple time points post-dose (up to 72 hours) Area Under the Plasma Concentration-Time Curve from Time Zero to Last Quantifiable Concentration (AUC0-t) of Mitapivat Under Fasted Conditions Pre-dose and multiple time points post-dose (up to 72 hours) Area Under the Plasma Concentration-Time Curve from Time Zero to Infinity (AUC0-∞) of Mitapivat Under Fasted Conditions Pre-dose and multiple time points post-dose (up to 72 hours)
- Secondary Outcome Measures
Name Time Method Relative Bioavailability (Frel) Under Fasted and Fed Conditions Pre-dose and multiple time points post-dose (up to 72 hours) AUC0-t of Mitapivat Under Fed Conditions Pre-dose and multiple time points post-dose (up to 72 hours) AUC0-∞ of Mitapivat Under Fed Conditions Pre-dose and multiple time points post-dose (up to 72 hours) Cmax of Mitapivat Under Fed Conditions Pre-dose and multiple time points post-dose (up to 72 hours) Tmax of Mitapivat Under Fed Conditions Pre-dose and multiple time points post-dose (up to 72 hours) Area Under the Plasma Concentration-Time Curve from Time Zero to Twelve Hours (AUC0-12) of Mitapivat Under Fasted and Fed Conditions Pre-dose and multiple time points post-dose (up to 72 hours) Apparent Plasma Terminal Elimination Half-life (t½) of Mitapivat Under Fasted and Fed Conditions Pre-dose and multiple time points post-dose (up to 72 hours) Apparent Total Plasma Clearance (CL/F) of Mitapivat Under Fasted and Fed Conditions Pre-dose and multiple time points post-dose (up to 72 hours) Apparent Volume of Distribution (Vz/F) of Mitapivat Under Fasted and Fed Conditions Pre-dose and multiple time points post-dose (up to 72 hours) Apparent Terminal Elimination Rate Constant (λz) of Mitapivat Under Fasted and Fed Conditions Pre-dose and multiple time points post-dose (up to 72 hours) Number of Participants With AEs, Graded by Severity Up to approximately 9 weeks Number of Participants With Adverse Event (AEs) Up to approximately 9 weeks Number of Participants With Clinically Significant Abnormal Clinical Laboratory Values Up to approximately 9 weeks Number of Participants With Clinically Significant Abnormal Findings for 12-lead Electrocardiogram (ECG) Parameters Up to approximately 9 weeks Number of Participants With Clinically Significant Abnormal Findings for Vital Signs Parameters Up to approximately 9 weeks Number of Participants With Clinically Significant Abnormal Physical Examination Findings Up to approximately 9 weeks
Trial Locations
- Locations (1)
Covance Clinical Research Unit Inc.
🇺🇸Dallas, Texas, United States