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

NCT ID: NCT04565678

Last Updated: 2020-12-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 32 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-09-21
• Study Completion Date: 2020-12-03

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.

Conditions

Healthy Volunteers

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment Sequence 1: ABCD

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.

Group Type: EXPERIMENTAL

Mitapivat tablets

Intervention Type: DRUG

Oral tablets

Mitapivat coated granules

Intervention Type: DRUG

Oral coated granules

Treatment Sequence 2: BDAC

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.

Group Type: EXPERIMENTAL

Mitapivat tablets

Intervention Type: DRUG

Oral tablets

Mitapivat coated granules

Intervention Type: DRUG

Oral coated granules

Treatment Sequence 3: CADB

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.

Group Type: EXPERIMENTAL

Mitapivat tablets

Intervention Type: DRUG

Oral tablets

Mitapivat coated granules

Intervention Type: DRUG

Oral coated granules

Treatment Sequence 4: DCBA

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.

Group Type: EXPERIMENTAL

Mitapivat tablets

Intervention Type: DRUG

Oral tablets

Mitapivat coated granules

Intervention Type: DRUG

Oral coated granules

Interventions

Mitapivat tablets

Oral tablets

Intervention Type: DRUG

Mitapivat coated granules

Oral coated granules

Intervention Type: DRUG

Other Intervention Names

AG-348; AG-348 sulfate hydrate; Mitapivat sulfate; AG-348; AG-348 sulfate hydrate; Mitapivat sulfate

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Agios Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Covance Clinical Research Unit Inc.

Dallas, Texas, United States

Countries

United States

Other Identifiers

AG348-C-019

Identifier Type: -

Identifier Source: org_study_id