Clinical trial NCT05386758: A Study to Evaluate Molnupiravir (MK-4482; MOV) in Participants With Severe Renal Impairment (MK-4482-003)
Official title: An Open-Label, Single-Dose Study to Evaluate the Pharmacokinetics of Molnupiravir (MK-4482; MOV) in Participants With Severe Renal Impairment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Renal Impairment
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2022-05-23
Enrollment: 16
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: 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.


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

Primary outcomes:
measure: Area Under the Curve From Time 0 to Infinity (AUC0-inf) of N-hydroxycytidine (NHC)
timeFrame: Predose, 0.5,1.5, 2, 4, 6, 8, 12, 24, 48 and 72 hours postdose
measure: Maximum Plasma Concentration (Cmax) of NHC
timeFrame: Predose, 0.5,1.5, 2, 4, 6, 8, 12, 24, 48 and 72 hours postdose
measure: Number of Participants Who Experienced an Adverse Event (AE)
timeFrame: Up to Day 15
Secondary outcomes:
measure: Amount of Dose Administered Excreted in Urine (Ae) of N-hydroxycytidine (NHC)
timeFrame: Predose, 4, 8, 12 and 24 hours postdose
measure: Fraction of the Dose Administered Excreted in Urine (Fe) of NHC
timeFrame: Predose, 4, 8, 12 and 24 hours postdose
measure: Renal Clearance (CLr) of NHC
timeFrame: Predose, 4, 8, 12 and 24 hours postdose
Other outcomes:
Locations:
city: Hallandale Beach
country: United States
facility: Velocity Clinical Research, Hallandale Beach ( Site 0005)
state: Florida
city: Miami
country: United States
facility: Advanced Pharma CR, LLC ( Site 0004)
state: Florida
city: Tampa
country: United States
facility: Genesis Clinical Research, LLC ( Site 0003)
state: Florida
city: Philadelphia
country: United States
facility: Thomas Jefferson University-Pharmacology, Physiology and Cancer Biology ( 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.