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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: Mitapivat tablets; Drug: Mitapivat coated granules

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75247
      • Covance Clinical Research Unit Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Mitapivat tablets; Oral tablets; Other Names: AG-348; AG-348 sulfate hydrate; Mitapivat sulfate; Drug: Mitapivat coated granules; Oral coated granules; Other Names: AG-348; AG-348 sulfate hydrate; Mitapivat sulfate
Experimental: 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.	Drug: Mitapivat tablets; Oral tablets; Other Names: AG-348; AG-348 sulfate hydrate; Mitapivat sulfate; Drug: Mitapivat coated granules; Oral coated granules; Other Names: AG-348; AG-348 sulfate hydrate; Mitapivat sulfate
Experimental: 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.	Drug: Mitapivat tablets; Oral tablets; Other Names: AG-348; AG-348 sulfate hydrate; Mitapivat sulfate; Drug: Mitapivat coated granules; Oral coated granules; Other Names: AG-348; AG-348 sulfate hydrate; Mitapivat sulfate
Experimental: 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.	Drug: Mitapivat tablets; Oral tablets; Other Names: AG-348; AG-348 sulfate hydrate; Mitapivat sulfate; Drug: Mitapivat coated granules; Oral coated granules; Other Names: AG-348; AG-348 sulfate hydrate; Mitapivat sulfate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Agios Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): September 21, 2020
• Primary Completion (Actual): December 3, 2020
• Study Completion (Actual): December 3, 2020

Study Registration Dates

• First Submitted: September 22, 2020
• First Submitted That Met QC Criteria: September 22, 2020
• First Posted (Actual): September 25, 2020

Study Record Updates

• Last Update Posted (Actual): December 10, 2020
• Last Update Submitted That Met QC Criteria: December 9, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Other Study ID Numbers: AG348-C-019

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No