Clinical trial NCT05386589: A Study to Evaluate Molnupiravir (MK-4482) in Participants With Moderate Hepatic Impairment (MK-4482-016)
Official title: An Open-Label, Single-Dose Clinical Study to Evaluate the Pharmacokinetics of Molnupiravir (MK-4482) in Participants With Moderate Hepatic Impairment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hepatic Impairment
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2022-05-23
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the pharmacokinetics (PK) of N-hydroxycytidine (NHC) following a single oral dose of molnupiravir in participants 18 to 75 years (inclusive) with moderate hepatic impairment and healthy matched controls.


Eligibility criteria: The key inclusion and exclusion criteria include but are not limited to the following:

Inclusion Criteria:

* Has a BMI ≥18.5 and ≤35 kg/m2
* Diagnosis of chronic (\>6 months) stable Hepatic Impairment (HI) with features of cirrhosis due to any etiology (Moderate HI arm only)
* Has a score on the Child-Pugh scale ranging from 7 to 9 (Moderate HI arm only)
* In good health (except for Moderate HI)

Exclusion Criteria:

* Anticipated survival of \<3 months (Moderate HI arm only)
* Received antiviral and/or immune modulating therapy (Moderate HI only) for Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV) within 90 days prior to study start
* History of clinically significant abnormalities or diseases (Healthy matched arm only).
* History of cancer
* Major surgery and/or donated or lost 1 unit of blood
* Taking medications to treat chronic medical conditions and has not been on a stable regimen for at least 1 month (Moderate HI arm only) and/or is unable to withhold the use of the medication(s) within 4 hours prior to and 8 hours after administration of the study drug.

Primary outcomes:
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-∞) of Plasma N-Hydroxycitidine (NHC)
timeFrame: Day 1: Predose and 0.5, 1.5, 2, 4, 6, 8, 12, 24, 48, and 72 hours postdose
measure: Maximum Plasma Concentration (Cmax) of NHC
timeFrame: Day 1: Predose and 0.5, 1.5, 2, 4, 6, 8, 12, 24, 48, and 72 hours postdose
Secondary outcomes:
measure: Number of Participants Experiencing ≥1 Adverse Event (AE)
timeFrame: Up to ~ 14 days
Other outcomes:
Locations:
city: Hollywood
country: United States
facility: Research Centers of America ( Hollywood ) ( Site 0002)
state: Florida
city: Miami
country: United States
facility: Clinical Pharmacology of Miami ( Site 0003)
state: Florida
city: Philadelphia
country: United States
facility: Thomas Jefferson University - Pharmacology and Experimental Therapeutics ( Site 0001)
state: Pennsylvania
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Duncan KE, Carstens RP, Butterfield KL, Jin Y, Inbody LR, Schaeffer AK, Matthews CZ, Zhao T, Patel S, Maas BM, Cheng MH, Stoch SA. Assessment of pharmacokinetics and tolerability following single-dose administration of molnupiravir in participants with hepatic or renal impairment. Clin Transl Sci. 2024 Dec;17(12):e70073. doi: 10.1111/cts.70073.