A Study to Assess the Relative Bioavailability and Effect of Food on the Coated Granule Formulation of Mitapivat in Healthy Participants

Study Overview
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Brief Summary
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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.

Official Title
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A Phase 1, Open-label, Randomized 4-period Crossover Study to Assess the Relative Bioavailability and Effect of Food on the Coated Granule Formulation of Mitapivat in Healthy Subjects

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: Mitapivat tablets
* Drug: Mitapivat coated granules


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Sequence 1: ABCD<br>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. | Drug: Mitapivat tablets<br>* Oral tablets<br>* Other names: Mitapivat sulfate;Drug: Mitapivat coated granules<br>* Oral coated granules<br>* Other names: Mitapivat sulfate;|
| Experimental: Treatment Sequence 2: BDAC<br>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. | Drug: Mitapivat tablets<br>* Oral tablets<br>* Other names: Mitapivat sulfate;Drug: Mitapivat coated granules<br>* Oral coated granules<br>* Other names: Mitapivat sulfate;|
| Experimental: Treatment Sequence 3: CADB<br>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. | Drug: Mitapivat tablets<br>* Oral tablets<br>* Other names: Mitapivat sulfate;Drug: Mitapivat coated granules<br>* Oral coated granules<br>* Other names: Mitapivat sulfate;|
| Experimental: Treatment Sequence 4: DCBA<br>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. | Drug: Mitapivat tablets<br>* Oral tablets<br>* Other names: Mitapivat sulfate;Drug: Mitapivat coated granules<br>* Oral coated granules<br>* Other names: Mitapivat sulfate;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | 
| Time to Reach Maximum Observed Concentration (Tmax) of Mitapivat Under Fasted Conditions |  | Pre-dose and multiple time points post-dose (up to 72 hours) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax of Mitapivat Under 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) | 
| Tmax of Mitapivat Under Fed Conditions |  | Pre-dose and multiple time points post-dose (up to 72 hours) | 
| Relative Bioavailability (Frel) Under Fasted and 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 Adverse Event (AEs) |  | Up to approximately 9 weeks | 
| Number of Participants With AEs, Graded by Severity |  | 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 |