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

Study Overview
=================
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.

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

Conditions
-----------------
Renal Impairment

Intervention / Treatment
-----------------
* Drug: Molnupiravir


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Panel A - Severe Renal Impairment Group<br>Participants with severe renal impairment will receive a single oral 800 mg dose of molnupiravir. | Drug: Molnupiravir<br>* Four 200 mg capsules administered orally as a single dose<br>* Other names: MK-4482; MOV; EIDD-2801;|
| Experimental: Panel B - Healthy Control Group<br>Participants in the healthy mean matched control group will receive a single oral 800 mg dose of molnupiravir. | Drug: Molnupiravir<br>* Four 200 mg capsules administered orally as a single dose<br>* Other names: MK-4482; MOV; EIDD-2801;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | 
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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) | 
| 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) | 
| 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) |