A Study to Evaluate Molnupiravir (MK-4482; MOV) in Participants With Severe Renal Impairment (MK-4482-003)

Phase 1

Completed

• Conditions: Renal Impairment
• Interventions: Drug: Molnupiravir

• Registration Number: NCT05386758
• Lead Sponsor: Merck Sharp & Dohme LLC

Brief Summary

This purpose of this study is to evaluate the plasma pharmacokinetics (PK) of N-hydroxycytidine (NHC), the nucleoside metabolite of molnupiravir, after a single oral dose of 800 mg molnupiravir in participants with severe renal impairment compared to healthy mean matched control participants. This study will also assess the safety and tolerability of molnupiravir in participants with severe renal impairment and the urinary excretion of NHC after a single oral dose of 800 mg molnupiravir in participants with severe renal impairment compared to healthy mean matched control participants. The primary hypothesis is that the plasma PK participants with severe renal impairment will be similar to that observed in the healthy mean matched control participants.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-05-18
• Study First Submitted QC: 2022-05-18
• Study First Posted: 2022-05-23
• Study Start: 2022-06-29
• Primary Completion: 2023-02-04
• Study Completion: 2023-03-01
• Results First Submitted: 2024-01-19
• Results First Submitted QC: 2024-01-19
• Results First Posted: 2024-07-05
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-15
• Last Update Posted: 2025-01-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 16

Inclusion Criteria

The key Inclusion Criteria include but are not limited to the following:

• Body mass index (BMI) ≥18.5 kg/m^2 and ≤35 kg/m^2
• Healthy participants: Baseline estimated glomerular filtration rate (eGFR) ≥90 mL/min based on the 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Creatinine equation
• Severe renal impairment participants: Baseline estimated glomerular filtration rate (eGFR) <30 mL/min based on the 2021 CKD-EPI Creatinine equation

Exclusion Criteria

The key Exclusion Criteria include but are not limited to the following:

• Positive for hepatitis B surface antigen (HBsAg), hepatitis C antibodies or human immunodeficiency virus (HIV)
• History of major surgery, donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to the prestudy (screening) visit

Severe renal impairment participants:

• History or presence of renal artery stenosis
• Had a renal transplant
• Currently taking medications to treat chronic medical conditions associated with renal disease if participant has not been on a stable regimen for at least 1 month and/or is unable to withhold the use of medication(s) within 4 hours prior to and 8 hours after administration of the study drug

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Panel A - Severe Renal Impairment Group	Molnupiravir	Participants with severe renal impairment will receive a single oral 800 mg dose of molnupiravir.
Panel B - Healthy Control Group	Molnupiravir	Participants in the healthy mean matched control group will receive a single oral 800 mg dose of molnupiravir.

Primary Outcome Measures

Name	Time	Method
Maximum Plasma Concentration (Cmax) of NHC	Predose, 0.5,1.5, 2, 4, 6, 8, 12, 24, 48 and 72 hours postdose	Blood for plasma samples was collected at pre-specified time points to determine the Cmax of NHC.
Area Under the Curve From Time 0 to Infinity (AUC0-inf) of N-hydroxycytidine (NHC)	Predose, 0.5,1.5, 2, 4, 6, 8, 12, 24, 48 and 72 hours postdose	Blood for plasma samples was collected at pre-specified time points to determine the AUC0-inf of NHC.
Number of Participants Who Experienced an Adverse Event (AE)	Up to Day 15	An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE was therefore any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who experienced an AE were reported.

Secondary Outcome Measures

Name	Time	Method
Fraction of the Dose Administered Excreted in Urine (Fe) of NHC	Predose, 4, 8, 12 and 24 hours postdose	Urine was collected at pre-specified time points to determine the Fraction of the dose administered excreted in urine (Fe) of NHC.
Amount of Dose Administered Excreted in Urine (Ae) of N-hydroxycytidine (NHC)	Predose, 4, 8, 12 and 24 hours postdose	Urine was collected at pre-specified time points to determine the amount of dose Administered excreted in urine (Ae) of NHC.
Renal Clearance (CLr) of NHC	Predose, 4, 8, 12 and 24 hours postdose	Urine will be collected at pre-specified time points to determine the Renal Clearance (CLr) of NHC

Trial Locations

Locations (4)

Advanced Pharma CR, LLC ( Site 0004); 🇺🇸 Miami, Florida, United States

Velocity Clinical Research, Hallandale Beach ( Site 0005); 🇺🇸 Hallandale Beach, Florida, United States

Genesis Clinical Research, LLC ( Site 0003); 🇺🇸 Tampa, Florida, United States

Thomas Jefferson University-Pharmacology, Physiology and Cancer Biology ( Site 0001); 🇺🇸 Philadelphia, Pennsylvania, United States