MK-5684 for Kidney Disease

Recruiting at 1 trial location

Overseen By Toll Free Number

Age: 18+

Sex: Male

Trial Phase: Phase 1

Sponsor: Merck Sharp & Dohme LLC

Disqualifiers: Adrenal insufficiency, Hepatic impairment, Hypotension, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: 1 day

24 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, since participants with end-stage renal disease must continue their hemodialysis, it might be possible to stay on some existing treatments. Please consult with the trial coordinators for specific guidance.

Is MK-5684 (Fludrocortisone acetate, Prednisone) safe for humans?

The research articles provided do not contain specific safety data for MK-5684, Fludrocortisone acetate, or Prednisone in humans. ^{1 2 3 4 5}

How is the drug MK-5684 for kidney disease different from other treatments?

The drug MK-5684, combined with Fludrocortisone acetate and Prednisone, may offer a unique approach to treating kidney disease by potentially targeting different pathways compared to standard treatments like mineralocorticoid receptor antagonists, which are commonly used for diabetic kidney disease. This combination could provide a novel mechanism of action or benefit for patients who do not respond well to existing therapies. ^{6 7 8 9 10}

What is the purpose of this trial?

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.

Research Team

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Eligibility Criteria

This trial is for males with severe renal impairment or end-stage renal disease who are on stable hemodialysis, as well as healthy individuals. Participants should be non-smokers or moderate smokers and have a BMI between 18.0 and 42.0 kg/m^2. Those with normal kidney function can also join to serve as a comparison group.

Inclusion Criteria

I am willing to participate in this study.

I have smoked 10 or fewer cigarettes daily for the last 3 months.

My kidney function is normal.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive a single oral dose of MK-5684 and Hormone replacement therapy (HRT) under fasting and fed conditions, with hemodialysis for ESRD group

1 day

1 visit (in-person)

Follow-up

Participants are monitored for pharmacokinetics and safety, with blood and dialysate samples collected

72 hours

Multiple time points for sample collection

Safety Monitoring

Participants are monitored for adverse events and discontinuation due to adverse events

Up to 21 days

Treatment Details

Interventions

• Fludrocortisone acetate
• MK-5684
• Prednisone

Trial Overview The study examines how the body processes MK-5684 in people with severe kidney issues compared to healthy individuals. It will also look at the effects of MK-5684 after hemodialysis treatments in those with serious kidney conditions.

Participant Groups

Group I: Group 3: Healthy Participants Experimental Treatment 3 Interventions

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).

Group II: Group 2: End-stage renal disease (ESRD) Experimental Treatment 3 Interventions

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.

Group III: Group 1: Severe Renal Impairment (RI) Experimental Treatment 3 Interventions

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).

Who Is Running the Clinical Trial?

Merck Sharp & Dohme LLC

Lead Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Findings from Research

In a study of 267 predialysis patients with chronic kidney disease (CKD), 69.3% experienced at least one adverse safety event, highlighting the high risk of complications in this population.

The most common adverse events reported were hypoglycemia in diabetic patients and hyperkalemia (high potassium levels), with significant co-occurrences of these events, indicating a need for better safety monitoring in CKD patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-reported and actionable safety events in CKD. Ginsberg, JS., Zhan, M., Diamantidis, CJ., et al.[2021]

In a 1-year study involving 182 outpatients with advanced chronic kidney disease (CKD), the eKidneyCare app significantly reduced medication discrepancies compared to the MyMedRec app, indicating better medication management.

eKidneyCare not only lowered the total number of discrepancies but also reduced the severity of clinically relevant discrepancies, including those that could potentially cause serious harm, highlighting its effectiveness in improving medication safety for high-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Digital Applications Targeting Medication Safety in Ambulatory High-Risk CKD Patients: Randomized Controlled Clinical Trial. Ong, SW., Jassal, SV., Porter, EC., et al.[2023]

Recent large trials involving over 12,000 participants indicate that finerenone, when added to existing treatments for diabetic kidney disease, can modestly improve kidney and cardiovascular outcomes, particularly in patients with proteinuria.

While there is a concern about hyperkalaemia (high potassium levels), finerenone appears to have a lower incidence of this side effect compared to other treatments, and new potassium-binding agents may help further reduce this risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Finerenone: a new mineralocorticoid receptor antagonist to beat chronic kidney disease. Raj, R.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

Patient-reported and actionable safety events in CKD. [2021]

2. Germany pubmed.ncbi.nlm.nih.gov

Gabapentinoid dosing and adverse events in patients with chronic kidney disease. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Digital Applications Targeting Medication Safety in Ambulatory High-Risk CKD Patients: Randomized Controlled Clinical Trial. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Drug Disposition Issues in CKD: Implications for Drug Discovery and Regulatory Approval. [2016]

5. United States pubmed.ncbi.nlm.nih.gov

Dose adjustment of rheumatology and allergy/immunology medications in chronic kidney disease: awareness and knowledge among internal medicine housestaff. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Pharmacotherapy considerations with finerenone in the treatment of chronic kidney disease associated with type 2 diabetes. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Finerenone: a new mineralocorticoid receptor antagonist to beat chronic kidney disease. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

Diabetes management in chronic kidney disease: a consensus report by the American Diabetes Association (ADA) and Kidney Disease: Improving Global Outcomes (KDIGO). [2023]

9. United States pubmed.ncbi.nlm.nih.gov

Diabetes Management in Chronic Kidney Disease: A Consensus Report by the American Diabetes Association (ADA) and Kidney Disease: Improving Global Outcomes (KDIGO). [2023]

10. United States pubmed.ncbi.nlm.nih.gov

KDOQI US Commentary on the KDIGO 2020 Clinical Practice Guideline for Diabetes Management in CKD. [2023]