A Study to Compare the Pharmacokinetics and Safety of Mitapivat 100 mg Tablet Formulation With Mitapivat 2 × 50 mg Tablet Formulation in Healthy Adult Participants

NCT04696393 | Completed Phase 1 FDA Drug

• 1 other identifier: AG348-C-021
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

The primary purpose of this study is to characterize and compare the pharmacokinetic profiles of mitapivat following a single dose administration of 100 mg mitapivat in two tablet formulations (50 mg and 100 mg tablet strengths) in healthy adult participants.

Conditions

Healthy Volunteers

Outcome Measures

Primary Outcomes (8)

• Area Under the Plasma Concentration Versus Time Curve (AUC) of Mitapivat From Time 0 to the Last Quantifiable Concentration (AUC0-t)

  Pre-dose and multiple time points post-dose (up to 120 hours)

• AUC of Mitapivat From Time 0 Extrapolated to Infinity (AUC0-inf)

  Pre-dose and multiple time points post-dose (up to 120 hours)

• Maximum Observed Plasma Concentration (Cmax) of Mitapivat

  Pre-dose and multiple time points post-dose (up to 120 hours)

• Time to Maximum Observed Plasma Concentration (Tmax) of Mitapivat

  Pre-dose and multiple time points post-dose (up to 120 hours)

• Apparent Terminal Elimination Rate Constant (λZ) of Mitapivat

  Pre-dose and multiple time points post-dose (up to 120 hours)

• Terminal Phase Half-life (t1/2) of Mitapivat

  Pre-dose and multiple time points post-dose (up to 120 hours)

• Apparent Oral Clearance (CL/F) of Mitapivat

  Pre-dose and multiple time points post-dose (up to 120 hours)

• Apparent Volume of Distribution (Vd/F) of Mitapivat

  Pre-dose and multiple time points post-dose (up to 120 hours)

Secondary Outcomes (5)

• Number of Participants With Adverse Events (AEs)

  Up to approximately 18 days

• Number of Participants With Clinically Significant Abnormal Clinical Laboratory Values

  Up to approximately 18 days

• Number of Participants With Clinically Significant Abnormal Findings for Vital Sign Parameters

  Up to approximately 18 days

• Number of Participants With Clinically Significant Abnormal Findings for 12-lead Electrocardiogram (ECG) Parameters

  Up to approximately 18 days

• Number of Participants With Clinically Significant Abnormal Physical Examination Findings

  Up to approximately 18 days

Study Arms (2)

Treatment Sequence 1: AB

EXPERIMENTAL

Participants will receive Treatment A (mitapivat 100 milligram \[mg\] tablet formulation, orally, under fasted conditions once on Day 1 of Period 1), followed by Treatment B (mitapivat 2 x 50 mg tablet formulation, orally, under fasted conditions once on Day 1 of Period 2). Each treatment period will be separated by a washout period of at least 7 days.

Drug: Mitapivat tablet

Treatment Sequence 1: BA

EXPERIMENTAL

Participants will receive Treatment B (mitapivat 2 x 50 mg tablet formulation, orally, under fasted conditions once on Day 1 of Period 1), followed by Treatment A (mitapivat 100 mg tablet formulation, orally, under fasted conditions once on Day 1 of Period 2). Each treatment period will be separated by a washout period of at least 7 days.

Drug: Mitapivat tablet

Interventions

Mitapivat tablet DRUG

Oral tablets

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

Treatment Sequence 1: AB; Treatment Sequence 1: BA

Eligibility Criteria

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

You may qualify if:

• Has the ability to understand the requirements of the study and a willingness to comply with all study procedures and has provided written informed consent before any study-related procedures are conducted, and is willing to comply with all study procedures for the duration of the study;
• Has a body mass index (BMI) ≥18 and ≤32 kilograms per square meter (kg/m\^2), at screening;
• Has a body weight ≥50 kg at screening;
• Is medically healthy, with no clinically significant conditions or abnormalities, as determined by the investigator or designee, through evaluation of medical history and vital sign measurements, 12-lead ECG results, physical examination findings, and clinical laboratory test results (congenital nonhemolytic hyperbilirubinemia \[eg, suspicion of Gilbert's syndrome based on total and direct bilirubin\] is not acceptable) at screening and check-in;
• If female:
• Is of childbearing potential and agrees to either abstain from sexual intercourse with a male partner or agrees to use a highly effective form of contraception, beginning at screening and continuing throughout the study and for 28 days after dosing or is postmenopausal (defined as 12 months or more continuously with no menses), or
• Has a documented medical history of tubal ligation or hysterectomy;
• 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 (even if vasectomized):
• Agrees to either abstain from sexual intercourse with a female partner, or
• Agrees to use a highly effective form of contraception (as defined above), starting at screening and continuing until 90 days after the final dose of mitapivat, and
• Agrees to not donate sperm throughout the entirety of the study until 90 days after the final dose of mitapivat;
• Agrees to abstain from any alcohol consumption, starting 72 hours prior to check-in and continuing until the follow-up telephone call;
• Agrees to refrain from marijuana- or cannabinol-containing products for 7 days prior to screening until after the follow-up telephone call.

You may not qualify if:

• At screening, presents with a condition or has a medical history that, in the opinion of the investigator, may potentially interfere with study drug absorption, distribution, metabolism, and/or excretion (eg, malabsorption \[including due to cystic fibrosis, lactose intolerance, celiac disease\]);
• At screening, presents with a surgical history that, in the opinion of the investigator, may potentially interfere with study drug absorption, distribution, metabolism, and/or excretion (eg, cholecystectomy). Participants who have undergone abdominal surgery or any other major surgical procedure within 6 months prior to screening, must not be enrolled;
• Has a history or a presence of a primary malignancy, with the exception of a malignancy that has been curatively treated and for which the participant has displayed no evidence of disease within 12 months prior to screening;
• Has a known history or presence of liver disease;
• Is pregnant or breastfeeding;
• 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;
• Has liver test results including alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, and total bilirubin that are above the upper limit of normal at screening or check-in (out-of-range test results may be repeated once at screening and check-in, if needed);
• Has estimated glomerular filtration rate (eGFR) \<60 milliliters per minute (mL/min)/1.73 m\^2 using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2009 equation;
• Has platelet, hemoglobin, or hematocrit test results that are below the lower limit of normal at screening or check-in (out-of-range test results may be repeated once at screening and check-in, if needed);
• Has confirmed (ie, 2 consecutive measurements) systolic blood pressure (BP) \>150 or \<90 millimeters of mercury (mmHg), diastolic blood pressure (BP) \>90 or \<50 mmHg, and pulse rate \>100 or \<45 beats per minute (bpm) at screening and check-in;
• Has clinically significant cardiac history or presence of ECG findings as determined by the investigator at screening and check-in, including any of the following:
• Abnormal sinus rhythm (heart rate \[HR\] lower than 45 bpm and higher than 100 bpm);
• Risk factors for torsades de pointes (eg, heart failure, cardiomyopathy, or family history of long QT syndrome);
• Sick sinus syndrome, second- or third-degree atrioventricular block myocardial infarction, pulmonary congestion, cardiac arrhythmia, prolonged QT interval, or conduction abnormalities;
• QT interval corrected for HR using Fridericia's formula (QTcF) \>450 milliseconds (msec) (male participants) or \>450 msec (female participants). In the event a QTcF value is outside of the reference range, it will be confirmed by 2 further repeat measurements, which will then be used to calculate a mean from the original value and the 2 repeat measurements;

Sponsors & Collaborators

• Agios Pharmaceuticals, Inc.: lead

Study Sites (1)

PPD Development, LP

Austin, Texas, 78744, 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: January 4, 2021
• First Posted: January 6, 2021
• Study Start: January 6, 2021
• Primary Completion: March 19, 2021
• Study Completion: March 19, 2021
• Last Updated: April 13, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)