Clinical trial NCT06814132: A Study to Evaluate the Effect of MK-5684 in Male Participants With Severe Renal Impairment (RI) and With End-stage Renal Disease (ESRD) (MK-5684-010)
Official title: An Open-Label, Single-Dose Study to Evaluate the Pharmacokinetics of MK-5684 in Male Participants With Severe Renal Impairment and With End-stage Renal Disease
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Kidney Failure, Chronic
End-Stage Kidney Disease
Renal Failure, Chronic
Renal Failure, End-Stage
Healthy Participants
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2025-02-07
Enrollment: 24
Sex: MALE
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: The goal of the study is to learn what happens to levels of MK-5684 in people with severe renal impairment and end-stage renal disease versus a healthy person's body over time. Researchers will compare what happens to MK-5684 after hemodialysis in people with severe renal impairment and end-stage renal disease versus healthy people.


Eligibility criteria: Inclusion Criteria:

Inclusion criteria include, but are not limited to:

All Participants

* Is a continuous non-smoker or moderate smoker (≤ 10 cigarettes per day or equivalent) for at least 3 months prior to the first dosing
* Has a body mass index (BMI) ≥ 18.0 and ≤ 42.0 kg/m\^2 at the screening visit

Participants with severe renal impairment (RI) (Group 1):

* Has severely impaired renal function as determined by estimated glomerular filtration rate (eGFR) using the 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation

Participants with end-stage renal disease (ESRD) (Group 2):

* Has ESRD maintained on stable outpatient regimen of intermittent high-flux hemodialysis (HD) (at least 3 times per week) for a minimum of 3 hours per dialysis session, using a complication free well-maintained arteriovenous fistula or arteriovenous graft, for at least 3 months prior to first dosing and is expected and planning to continue HD during the study and at least up to the follow-up visit

Healthy Control Participants (Group 3):

* Has normal renal function

Exclusion Criteria:

Exclusion criteria include, but are not limited to:

All Participants:

* Has a history or presence of any of the following: Adrenal insufficiency; Hepatic impairment; Clinically significant hypotension; cardiac arrhythmia; cardiac conduction abnormalities or recurrent unexplained syncopal events; Second- or third-degree atrioventricular (AV) heart block (except in participants with a functional artificial pacemaker); Clinically significant sick sinus syndrome; Any systemic fungal infection; Hypothyroidism; Chronic infection
* Has a first-degree relative with multiple unexplained syncopal events, unexplained cardiac arrest, or sudden cardiac death, or has a known family history of an inherited arrhythmia syndrome (including Brugada syndrome)
* Has a history of cancer (malignancy)
* Is positive for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV)

Participants with Severe RI (Group 1):

* Has a history or presence of renal artery stenosis
* Has had a renal transplant
* Has ESRD requiring HD

Participants with ESRD (Group 2):

* Has required frequent emergent HD (≥ 3) within a year prior to the first dosing
* Has a history or presence of renal artery stenosis.
* Has had a functioning renal transplant within the past 2 years

Primary outcomes:
measure: Area Under the Concentration Versus Time Curve from 0 to Infinity (AUC0-inf) After a Single Dose of MK-5684
timeFrame: At protocol specific time points pre-dose and up to 72 hours post-dose
measure: Area Under the Concentration Versus Time Curve From 0 to the Time of the Last Quantifiable Sample (AUC0-last) of MK-5684
timeFrame: At protocol specific time points pre-dose and up to 72 hours post-dose
measure: Area Under the Concentration Versus Time Curve From 0 to 24 Hours After Dosing (AUC0-24) of MK-5684
timeFrame: At protocol specific time points pre-dose and up to 24 hours post-dose
measure: Maximum Observed Drug Concentration (Cmax) After the Administration of a Given Dose of MK-5684
timeFrame: At protocol specific time points pre-dose and up to 72 hours post-dose
measure: Time to Maximum Observed Plasma Drug Concentration (Tmax) of MK-5684
timeFrame: At protocol specific time points pre-dose and up to 72 hours post-dose
measure: Apparent Terminal Half-Life (t½) of MK-5684
timeFrame: At protocol specific time points pre-dose and up to 72 hours post-dose
measure: Apparent Clearance (CL/F) of MK-5684
timeFrame: At protocol specific time points pre-dose and up to 72 hours post-dose
measure: Apparent Volume of Distribution During Terminal Phase (Vz/F) of MK-5684
timeFrame: At protocol specific time points pre-dose and up to 72 hours post-dose
Secondary outcomes:
measure: Number of Participants who Experience an Adverse Event (AE)
timeFrame: Up to ~21 days
measure: Number of Participants who Discontinue Study Intervention Due to an AE
timeFrame: Up to ~7 days
measure: Dialysis Clearance (CLD) of MK5684 Based on Plasma
timeFrame: At protocol specific time points pre-dose and up to 4.5 hours post-dose
measure: Concentration of Dialysate (CD) of MK-5684 Samples
timeFrame: At protocol specific time points pre-dose and up to 4.5 hours post-dose
measure: Amount of drug (AD) of MK-5684 recovered from each dialysate collection
timeFrame: At protocol specific time points pre-dose and up to 4.5 hours post-dose
Other outcomes:
Locations:
city: Orlando
country: United States
facility: Orlando Clinical Research Center ( Site 0002)
state: Florida
city: Chicago
country: United States
facility: Research by Design ( Site 0001)
state: Illinois
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: