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

NCT04565678 | Completed Phase 1 FDA Drug

• 1 other identifier: AG348-C-019
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (16)

• 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)

Study Arms (4)

Treatment Sequence 1: ABCD

EXPERIMENTAL

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; Drug: Mitapivat coated granules

Treatment Sequence 2: BDAC

EXPERIMENTAL

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; Drug: Mitapivat coated granules

Treatment Sequence 3: CADB

EXPERIMENTAL

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; Drug: Mitapivat coated granules

Treatment Sequence 4: DCBA

EXPERIMENTAL

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; Drug: Mitapivat coated granules

Interventions

Mitapivat tablets DRUG

Oral tablets

Also known as: AG-348, AG-348 sulfate hydrate, Mitapivat sulfate

Treatment Sequence 1: ABCD; Treatment Sequence 2: BDAC; Treatment Sequence 3: CADB; Treatment Sequence 4: DCBA

Mitapivat coated granules DRUG

Oral coated granules

Also known as: AG-348, AG-348 sulfate hydrate, Mitapivat sulfate

Treatment Sequence 1: ABCD; Treatment Sequence 2: BDAC; Treatment Sequence 3: CADB; Treatment Sequence 4: DCBA

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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;

Sponsors & Collaborators

• Agios Pharmaceuticals, Inc.: lead

Study Sites (1)

Covance Clinical Research Unit Inc.

Dallas, Texas, 75247, United States

Location

MeSH Terms

Interventions

mitapivat

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 22, 2020
• First Posted: September 25, 2020
• Study Start: September 21, 2020
• Primary Completion: December 3, 2020
• Study Completion: December 3, 2020
• Last Updated: December 10, 2020

Record last verified: 2020-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)