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)

Merck Sharp & Dohme (MSD)

Status and phase: Enrolling; Phase 1

Conditions: End-Stage Kidney Disease; Healthy Participants; Renal Failure, End-Stage; Renal Failure, Chronic; Kidney Failure, Chronic

Treatments: Drug: Prednisone; Drug: Fludrocortisone acetate; Drug: MK-5684

Study type: Interventional

Funder types: Industry

Identifiers

NCT06814132

CA43216 (Other Identifier)

5684-010

MK-5684-010 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 24 estimated patients

Sex: Male

Ages: 18 to 85 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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24 participants in 3 patient groups

Group 1: Severe Renal Impairment (RI)

Experimental group

Description:

Participants will receive a single oral dose of MK-5684 under fasting conditions (on an empty stomach after a 10-hour overnight fast) on Day 1 and a single dose of Hormone replacement therapy (HRT) (prednisone and fludrocortisone) administered approximately 4.5 hours after MK-5684 dosing under fed conditions (eating a normal meal).

Treatment:

Drug: MK-5684

Drug: Fludrocortisone acetate

Drug: Prednisone

Group 2: End-stage renal disease (ESRD)

Experimental group

Description:

Participants will receive a single oral dose of MK-5684 under fasting conditions (on an empty stomach after a 10-hour overnight fast) in Period 1 and Period 2. In Period 1, participants will receive a single oral dose of MK-5684 approximately 30 minutes prior to their normally scheduled hemodialysis (HD), followed by HRT under fed conditions (eating a normal meal) 4.5 hours after MK-5684 dosing. In Period 2, participants will receive a single oral dose of MK-5684 immediately followed by completion of their normally scheduled HD, and by HRT under fed conditions (eating a normal meal) 4.5 hours after MK-5684 dosing.

Treatment:

Drug: MK-5684

Drug: Fludrocortisone acetate

Drug: Prednisone

Group 3: Healthy Participants

Experimental group

Description:

Participants will receive a single oral dose of MK-5684 under fasting conditions (on an empty stomach after a 10-hour overnight fast) on Day 1 and a single dose of Hormone replacement therapy (HRT) (prednisone and fludrocortisone) administered approximately 4.5 hours after MK-5684 dosing under fed conditions (eating a normal meal).

Treatment:

Drug: MK-5684

Drug: Fludrocortisone acetate

Drug: Prednisone