A Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Mitapivat (AG-348) in Healthy Adult Participants

NCT04472832 | Completed Phase 1 FDA Drug

• 1 other identifier: AG348-C-014
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase 1, randomized, single-dose, double-blinded, 4-period, crossover study to evaluate the pharmacokinetics, safety, and tolerability of mitapivat in healthy adult participants under fasted and fed (high-fat meal) conditions. Secondary objectives include evaluating the effect of mitapivat on electrocardiogram (ECG) parameters, including concentration-QT interval corrected for heart rate (C-QTc) analysis under fasted conditions. The study will include a 28-day screening period, four 7-day treatment periods. Participants will receive a follow-up telephone call within 28 (±1) days after the last dose of study drug.

Conditions

Healthy Volunteers

Outcome Measures

Primary Outcomes (9)

• Area Under the Plasma Concentration Versus Time Curve (AUC) From Time 0 to the Last Quantifiable Concentration (AUC0-T) for Mitapivat Under Fasted and High-Fat Meal Conditions

  Predose and at various timepoints through 120 hours postdose within each 7-day period

• AUC From Time 0 Extrapolated to Infinity (AUC0-Inf) for Mitapivat Under Fasted and High-Fat Meal Conditions

  Predose and at various timepoints through 120 hours postdose within each 7-day period

• Maximum Observed Plasma Concentration (Cmax) for Mitapivat Under Fasted and High-Fat Meal Conditions

  Predose and at various timepoints through 120 hours postdose within each 7-day period

• Time to Reach Maximum Observed Plasma Concentration (Tmax) for Mitapivat Under Fasted and High-Fat Meal Conditions

  Predose and at various timepoints through 120 hours postdose within each 7-day period

• Apparent Terminal Elimination Half-Life (T1/2) for Mitapivat Under Fasted and High-Fat Meal Conditions

  Predose and at various timepoints through 120 hours postdose within each 7-day period

• Apparent Oral Clearance (CL/F) for Mitapivat Under Fasted and High-Fat Meal Conditions

  Predose and at various timepoints through 120 hours postdose within each 7-day period

• Apparent Terminal Elimination Rate Constant (Λz) for Mitapivat Under Fasted and High-Fat Meal Conditions

  Predose and at various timepoints through 120 hours postdose within each 7-day period

• Apparent Volume of Distribution (Vd/F) for Mitapivat Under Fasted and High-Fat Meal Conditions

  Predose and at various timepoints through 120 hours postdose within each 7-day period

• Relative Bioavailability (Frel; AUC0-Inf [fed]/AUC0-Inf [fasted]) for Fed Treatment Following Administration of Mitapivat 100-mg Dose

  Predose and at various timepoints through 120 hours postdose within each 7-day period

Secondary Outcomes (5)

• Percentage of Participants With Adverse Events (AEs)

  Up to approximately 8 weeks

• Percentage of Participants with Abnormalities in Clinical Laboratory Findings

  Up to approximately 8 weeks

• Percentage of Participants With Abnormalities in Vital Sign Measurements

  Up to approximately 8 weeks

• Percentage of Participants With Abnormalities in 12-lead Electrocardiogram (ECG) Results

  Up to approximately 8 weeks

• Percentage of Participants With Abnormalities in Physical Examination Findings

  Up to approximately 8 weeks

Study Arms (4)

Treatment A

PLACEBO COMPARATOR

Participants will receive a single oral dose of mitapivat-matching placebo under fasted conditions on Day 1 of each of 4 periods.

Drug: Placebo for Treatment A

Treatment B

EXPERIMENTAL

Participants will receive a single oral dose of mitapivat 100 milligrams (mg) and placebo under fasted conditions on Day 1 of each of 4 periods.

Drug: Mitapivat 100 mg; Drug: Placebo for Treatment B

Treatment C

EXPERIMENTAL

Participants will receive a single oral dose of mitapivat 100 mg and placebo under high-fat meal conditions on Day 1 of each of 4 periods.

Drug: Mitapivat 100 mg; Drug: Placebo for Treatment C

Treatment D

EXPERIMENTAL

Participants will receive a single oral dose of mitapivat 300 mg under fasted conditions on Day 1 of each of 4 periods.

Drug: Mitapivat 300 mg

Interventions

Placebo for Treatment A DRUG

6 tablets matched to mitapivat tablet

Treatment A

Mitapivat 100 mg DRUG

Two 50-mg tablets

Also known as: AG-348

Treatment B; Treatment C

Placebo for Treatment B DRUG

4 tablets matched to mitapivat tablet

Treatment B

Mitapivat 300 mg DRUG

Six 50-mg tablets

Also known as: AG-348

Treatment D

Placebo for Treatment C DRUG

4 tablets matched to mitapivat tablet

Treatment C

Eligibility Criteria

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

You may qualify if:

• Participant is male or female 18 to 55 years of age, inclusive;
• If female, is not currently pregnant or breastfeeding OR is of non-childbearing potential, defined as either:
• Being clinically infertile as the result of surgical sterilization, confirmed postmenopausal status, or another documented medical condition (eg, was born without a uterus) OR
• Agreeing to either abstain from sexual intercourse with a male partner OR agrees to use a highly effective form of contraception, beginning at the time of screening and continuing throughout the study and for 28 days after dosing. The following are considered highly effective forms of contraception: hormonal oral contraceptives, injectables, and patches; intrauterine devices; double-barrier methods (synthetic condom, diaphragm, or cervical cap used with spermicidal foam, cream, or gel); and male partner sterilization;
• If male, agrees to abstain from sexual intercourse with a female partner OR agrees to use a highly effective form of contraception, beginning at the time of screening and continuing throughout the study and for 90 days after dosing, AND to refrain from donating sperm for the duration of the study and for 90 days after dosing;
• Participant has a body mass index 18 to 32 kilograms per square meter (kg/m\^2), inclusive, at screening;
• Participant is considered by the investigator to be in good general health as determined by medical history, clinical laboratory test results, vital sign measurements, 12-lead ECG results, and physical examination findings at screening;
• Participant has no clinically significant history or presence of ECG findings as judged by the investigator at screening and check-in, including each criterion as follows:
• Normal sinus rhythm (heart rate \[HR\] between 45 beats per minute \[bpm\] and 100 bpm inclusive);
• QT interval corrected for HR using Fridericia's formula (QTcF) ≤450 milliseconds (msec);
• QRS interval ≤110 msec; and confirmed by manual over read if \>110 msec;
• PR interval between 120 and 220 msec;
• Participant agrees to comply with all protocol requirements;
• Participant is able to provide written informed consent.

You may not qualify if:

• Participant has any medical or surgical condition that, in the opinion of the investigator, could affect study drug absorption, distribution, metabolism, or excretion;
• Participant has undergone any major surgical procedure within the 3 months prior to screening;
• Participant has a history of any primary malignancy (including any melanoma or suspicious undiagnosed skin lesions), with the exception of in situ basal cell or squamous cell carcinomas of the skin, cervical carcinoma in situ, or other malignancies that have been curatively treated and for which the participant has displayed no evidence of disease within the 5 years prior to screening;
• Participant has glucose-6-phosphate-dehydrogenase deficiency;
• Participant has a known history or presence of liver disease.
• Participant has a positive test result for hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCVAb), or human immunodeficiency virus (HIV) types 1 or 2 antibodies at screening;
• Participant has liver function tests including alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, and total bilirubin that are greater than the upper limit of normal at screening or check-in (results may be repeated once);
• Participant has platelet count or hemoglobin and hematocrit values that are below the lower limit of normal at screening or check-in (results may be repeated once);
• Participant has a positive test result for drugs of abuse, alcohol, or cotinine (indicating active current smoking) at screening or before the first dose of study drug or throughout the study.
• Participant has used any prescription (excluding hormonal birth control) medications within 30 days (or 5 half-lives, whichever is longer) before the first dose of study drug or throughout the study;
• 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 or throughout the study;
• Participant has received study drug in another investigational study within 30 days (or 5 half-lives, whichever is longer) of dosing.
• Participant has donated blood or blood products \>450 milliliters (mL) within 30 days before the first dose of study drug.
• Participant has history or presence of:
• Risk factors for torsades de pointes (eg, heart failure, cardiomyopathy, or family history of long QT syndrome);

Sponsors & Collaborators

• Agios Pharmaceuticals, Inc.: lead

Study Sites (1)

PPD Development, LP

Austin, Texas, 78744, United States

Location

MeSH Terms

Interventions

mitapivat

Study Officials

• Medical Affairs

  Agios Pharmaceuticals, Inc.

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 13, 2020
• First Posted: July 15, 2020
• Study Start: June 17, 2020
• Primary Completion: November 23, 2020
• Study Completion: November 23, 2020
• Last Updated: February 18, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)