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

Completed · Phase 1

Conditions studied: Moderate Hepatic Impairment

In brief

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.

Key facts

Study ID

NCT05610657

Run by

Agios Pharmaceuticals, Inc.

People needed

20

Starts

2023-01-10

Expected to finish

2023-07-21

Last updated by the study team

2023-09-21

Who can join

Age: 18 and older, up to 65. Sex: any. Healthy volunteers: accepted.

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;
• Other than hepatic insufficiency with features of cirrhosis, hepatic impairment participants are in good health and clinically stable based on:
• stable hepatic function is defined as no recent [i.e., within the preceding 14 days] CS change in disease status according to the investigator's clinical judgment (e.g., no worsening of clinical signs of hepatic impairment, or no worsening of total bilirubin or prothrombin by more than 50%).
• the investigator's assessment including medical history and surgical history review, a defined complete physical examination, 12-lead ECG, vital signs, and clinical laboratory evaluations (clinical chemistry [including liver function tests], hematology, urinalysis, coagulation tests, thyroid function tests).
• Abnormal laboratory values (hepatic and nonhepatic) must be clinically acceptable by the investigator (or designee);
• Participants who need concomitant medications that are not prohibited during this study must have a medication regimen considered to be stable by the investigator. (e.g., no new drugs or significant changes to dosage(s) within 2 weeks [or 5 half-lives, whichever is longer] prior to study drug administration on Day 1; no changes expected during study conduct). Concomitant medications must be reviewed and approved by the investigator and Labcorp medical monitor (or designee).
• Anemia secondary to hepatic disease will be acceptable if hemoglobin is ≥8 grams per deciliter (g/dL) and anemia symptoms are not CS;
• Participants must have a platelet count ≥35 × 10\^9/L.

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)
• Risk factors for torsades de pointes (e.g., 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) (healthy male participants) or >470 msec (healthy female participants) or >480 msec for hepatically impaired participants; in the event a QTcF value is outside of the reference range, it will be confirmed by 2 repeat measurements, which will then be used to calculate a mean from the original value and the 2 repeat measurements.
• QRS interval >110 msec, confirmed by manual over read.
• PR interval <120 and >220 msec.
• Repeated or frequent syncope or vasovagal episodes.
• Hypertension, angina, bradycardia (if assessed as CS by the investigator), or severe peripheral arterial circulatory disorders.
• History of autonomic dysfunction.
• Has estimated glomerular filtration rate <60 mL/minute/1.73 m\^2 using Cockcroft-Gault equation;
• Administration of a coronavirus disease 2019 vaccine in the past 14 days prior to dosing;

Where it is running

• Orange County Research Center (OCRC) — Tustin, California, United States
• Clinical Pharmacology of Miami (CPMI) — Miami, Florida, United States
• Orlando Clinical Research Center (OCRC) — Orlando, Florida, United States

Full record on ClinicalTrials.gov

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