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

Renal Impairment Clinical Trial

Official title:

An Open-Label, Single-Dose Study to Evaluate the Pharmacokinetics of Molnupiravir (MK-4482; MOV) in Participants With Severe Renal Impairment

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05386758
• Other study ID #: 4482-003
• Secondary ID: MK-4482-003
• Status: Completed
• Phase: Phase 1
• Start date: June 29, 2022
• Est. completion date: March 1, 2023

Study information

• Verified date: March 2023
• Source: Merck Sharp & Dohme LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: March 1, 2023
• Est. primary completion date: February 4, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Renal Impairment
• Renal Insufficiency

Intervention

Drug:
• Molnupiravir
Four 200 mg capsules administered orally as a single dose

Locations

Country	Name	City	State
United States	Velocity Clinical Research, Hallandale Beach ( Site 0005)	Hallandale Beach	Florida
United States	Advanced Pharma CR, LLC ( Site 0004)	Miami	Florida
United States	Thomas Jefferson University-Pharmacology, Physiology and Cancer Biology ( Site 0001)	Philadelphia	Pennsylvania
United States	Genesis Clinical Research, LLC ( Site 0003)	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area Under the Curve From Time 0 to Infinity (AUC0-inf) of N-hydroxycytidine (NHC)	Blood for plasma samples will be collected at pre-specified time points to determine the AUC0-inf of NHC.	At designated time points (Up to 72 hours)
Primary	Maximum Plasma Concentration (Cmax) of NHC	Blood for plasma samples will be collected at pre-specified time points to determine the Cmax of NHC.	At designated time points (Up to 72 hours)
Secondary	Number of Participants who Experienced an Adverse Event (AE)	An AE is 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 can therefore be 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 will be reported.	Up to approximately 14 days
Secondary	Amount of dose administered excreted in urine (Ae) of N-hydroxycytidine (NHC)	Urine will be collected at pre-specified time points to determine the Ae of NHC.	At designated time points (Up to 24 hours)
Secondary	Fraction of the dose administered excreted in urine (Fe) of NHC	Urine will be collected at pre-specified time points to determine the Fe of NHC.	At designated time points (Up to 24 hours)
Secondary	Renal Clearance (CLr) of NHC	Urine will be collected at pre-specified time points to determine the CLr of NHC	At designated time points (Up to 24 hours)