A Phase 1, Open-label, Single-dose, Pharmacokinetic Study of Mitapivat in Subjects With Moderate Hepatic Impairment Compared to Matched Healthy Control Subjects With Normal Hepatic Function

Agios Pharmaceuticals, Inc.3 sites in 1 country20 target enrollmentJanuary 10, 2023

ConditionsModerate Hepatic Impairment

InterventionsMitapivat

DrugsMitapivat

Overview

Phase: Phase 1
Intervention: Mitapivat
Conditions: Moderate Hepatic Impairment
Sponsor: Agios Pharmaceuticals, Inc.
Enrollment: 20
Locations: 3
Primary Endpoint: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-t) of Mitapivat
Status: Completed
Last Updated: 2 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

The primary purpose of this study is to compare the pharmacokinetics (PK) of a single oral dose of mitapivat in participants with moderate hepatic impairment to that in matched healthy control participants with normal hepatic function.

Registry

clinicaltrials.gov

Start Date

January 10, 2023

End Date

July 21, 2023

Last Updated

2 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Agios Pharmaceuticals, Inc.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•For all Participants-
•Age: between 18 and 65 years of age;
•Men and women of any race;
•Body mass index (BMI) between 18.0 and 34.0 kilograms per square meter (kg/m\^2), inclusive with at least 50 kg of body weight;
•There should be no use of tobacco- or nicotine-containing products within 3 months prior to check-in until completion of the follow-up visit;
•Male participants must agree not to donate sperm from check-in until 90 days after completion of the follow-up visit;
•Females of childbearing potential will agree to use contraception;
•Able to comprehend the requirements of the study and willing to sign an informed consent form before any study related procedures are conducted and to abide by the study restrictions.
•For Participants with Normal Hepatic Function-
•In good health, determined by no clinically significant (CS) findings, as determined by the investigator, from medical and surgical history, physical examination, 12-lead ECG, vital signs measurements, and clinical laboratory evaluations (congenital nonhemolytic hyperbilirubinemia \[e.g., suspicion of Gilbert's syndrome based on total and direct bilirubin\] is not acceptable) at screening and check-in;

Exclusion Criteria

•For all Participants-
•Presence or history of any disorder that may prevent the successful completion of the study;
•Participant is pregnant or breastfeeding;
•Significant acute, new-onset illness (e.g., flu, gastroenteritis) within 2 weeks prior to dosing;
•Inability to swallow medication;
•Has a history of relevant drug and/or food allergies (i.e., allergy to study drug or excipients \[microcrystalline cellulose, croscarmellose sodium, sodium stearyl fumarate, mannitol, magnesium stearate, and the Opadry Blue II film-coat \[hypromellose, titanium dioxide, lactose monohydrate, triacetin, and FD\&C Blue #2\]);
•Surgical or medical history that, in the opinion of the investigator, may potentially interfere with study drug absorption, distribution, metabolism, and/or excretion. Participants who have undergone abdominal surgery or any other major surgical procedure within 6 months prior to screening, must not be enrolled; The investigator should be guided by evidence of any of the following:
•History of inflammatory bowel syndrome, gastritis, ulcers, gastrointestinal or rectal bleeding within the past 3 months.
•History of major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, or bowel resection.
•History of pancreatic injury or pancreatitis in the past 6 months; indications of impaired pancreatic function/injury as indicated by CS abnormal lipase or amylase.

Arms & Interventions

Mitapivat

Mitapivat tablet as a single oral dose, under fasted conditions on Day 1 to compare participants with normal hepatic function to participants with moderate hepatic function (Child-Pugh \[C-P\] Score B, score of 7 to 9).

Intervention: Mitapivat

Outcomes

Primary Outcomes

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

Time Frame: Pre-dose and at multiple timepoints post-dose up to Day 17

Maximum Plasma Concentration (Cmax) of Mitapivat

Time Frame: Pre-dose and at multiple timepoints post-dose up to Day 17

Area Under the Plasma Concentration-Time Curve From Time 0 (Predose) to Extrapolated to Infinity Time (AUC∞) of Mitapivat

Time Frame: Pre-dose and at multiple timepoints post-dose up to Day 17

Secondary Outcomes

Fraction Unbound (fu) for Mitapivat in Plasma(Pre-dose and at multiple timepoints post-dose up to Day 11)
Number of Participants With Adverse Events (AEs), AEs by Severity, and Relatedness to Study Treatment(Up to Day 17)
Apparent Total Clearance (CL/F) of Mitapivat(Pre-dose and at multiple timepoints post-dose up to Day 17)
Apparent Volume of Distribution During the Terminal Phase (Vz/F) of Mitapivat(Pre-dose and at multiple timepoints post-dose up to Day 17)
Time to Reach Cmax (tmax) of Mitapivat(Pre-dose and at multiple timepoints post-dose up to Day 17)
Terminal Elimination Half-life (t1/2) of Mitapivat(Pre-dose and at multiple timepoints post-dose up to Day 17)
Number of Participants With Abnormalities in Laboratory Evaluations, Based on Coagulation, Hematology, Clinical Chemistry and Urinalysis Test Results(Up to Day 12)
Number of Participants With Changes in 12-lead Electrocardiogram (ECG) Parameters(Up to Day 12)
Number of Participants With Changes in Vital Sign Measurements(Up to Day 12)
Number of Participants With Changes in Physical Examination Findings(Up to Day 12)