A Pharmacokinetic Study of Mitapivat in Participants With Moderate Hepatic Impairment Compared to Matched Healthy Control Participants With Normal Hepatic Function

NCT05610657 | Completed Phase 1 FDA Drug

• 1 other identifier: AG348-C-024
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 3

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.

Conditions

Moderate Hepatic Impairment

Keywords

AG-348; Healthy Volunteer; Hepatic Impairment; pharmacokinetic

Outcome Measures

Primary Outcomes (3)

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

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

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

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

• Maximum Plasma Concentration (Cmax) of Mitapivat

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

Secondary Outcomes (10)

• 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

• 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

• Fraction Unbound (fu) for Mitapivat in Plasma

  Pre-dose and at multiple timepoints post-dose up to Day 11

Study Arms (1)

Mitapivat

EXPERIMENTAL

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).

Drug: Mitapivat

Interventions

Mitapivat DRUG

Mitapivat tablets

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

Mitapivat

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;
• Serum electrolytes (sodium, potassium, chloride, bicarbonate, magnesium, and calcium) within normal limits or if deemed not CS by the investigator judgment in the case of minor abnormalities;
• Matched to participants with moderate hepatic impairment in sex, age (±10 years), and BMI (±20%).
• For Participants with Moderate Hepatic Impairment-
• Diagnosis of chronic (≥3 months prior to screening) and stable hepatic insufficiency (no acute episodes of illness or deterioration in hepatic function) as assessed by the investigator with a C-P classification score of 7 to 9 (moderate hepatic impairment). Evidence of liver disease should be corroborated by medical history;
• Have current, or a history of at least 1 physical sign consistent with a clinical diagnosis of liver cirrhosis;

You may not qualify if:

• 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.
• History of urinary obstruction or difficulty in voiding in the past 3 months.
• History or a presence of any 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. Current or history of hepatic carcinoma, hepatorenal syndrome, portacaval shunt surgery, or pleural effusion. Malignancy, including leukemia and lymphoma, within the last 5 years. Participants with localized, fully-treated carcinoma of the skin may be allowed with investigator (or designee) approval;
• Confirmed (e.g., 2 consecutive measurements) systolic blood pressure \>150 or \<90 millimeters of mercury (mmHg), diastolic blood pressure \>100 or \<50 mmHg, and pulse rate \>100 or \<40 beats per minute (bpm); (Note: Participants with vital signs outside the above ranges may be eligible if the investigator and Labcorp medical monitor deem the results are not CS.)
• 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 40 bpm and higher than 100 bpm)

Sponsors & Collaborators

• Agios Pharmaceuticals, Inc.: lead

Study Sites (3)

Orange County Research Center (OCRC)

Tustin, California, 92780, United States

Location

Clinical Pharmacology of Miami (CPMI)

Miami, Florida, 33014, United States

Location

Orlando Clinical Research Center (OCRC)

Orlando, Florida, 32809, 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: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 3, 2022
• First Posted: November 9, 2022
• Study Start: January 10, 2023
• Primary Completion: July 21, 2023
• Study Completion: July 21, 2023
• Last Updated: September 21, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)