MK-5684 for Kidney Disease

No longer recruiting at 1 trial location

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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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand how the new treatment, MK-5684, behaves in individuals with severe kidney issues and those with healthy kidneys. It will also examine the drug's interaction with hemodialysis, a common treatment for kidney failure. Participants with severe kidney problems, end-stage renal disease requiring regular dialysis, or healthy kidneys may be suitable for this study. As a Phase 1 trial, participants will be among the first to receive this treatment, aiding researchers in understanding its effects in people.

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 there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that MK-5684 is still under study to understand its safety and effects, particularly for individuals with kidney problems. Detailed safety information from earlier studies is not yet available. As this trial is in its early stages, MK-5684's safety in humans remains under evaluation.

Fludrocortisone acetate has been used to help individuals with kidney disease by lowering high potassium levels and improving blood pressure. Studies have found it effective, but it should be used cautiously in those with kidney issues due to possible side effects.

Prednisone, a widely used steroid, has been shown to help with kidney problems, though it can also cause side effects such as mood changes, increased appetite, or trouble sleeping.

Overall, the treatments in this trial are being tested for safety and effectiveness. Participants should be aware of potential risks and discuss them with the trial team. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about MK-5684 because it offers a new approach to treating kidney disease, especially for those with severe renal impairment or end-stage renal disease. Unlike other treatments that primarily focus on managing symptoms, MK-5684 is being explored for its potential to directly impact kidney function. This treatment introduces a novel active ingredient, MK-5684, which is used alongside hormone replacement therapy (prednisone and fludrocortisone), potentially offering a more comprehensive management strategy. Additionally, MK-5684's unique dosing regimen, including its timing with hemodialysis, might optimize its effectiveness, providing new hope for patients who require innovative solutions.

What evidence suggests that this trial's treatments could be effective for kidney disease?

This trial explores how the drug MK-5684 affects individuals with serious kidney issues, including severe renal impairment and end-stage renal disease. Participants will receive MK-5684, and researchers will examine how the drug behaves in the body, particularly after treatments like hemodialysis, which cleans the blood when kidneys fail. While limited information exists on its effectiveness for kidney disease, the study aims to understand the drug's function in various conditions, potentially leading to better treatments in the future. ^{2 6 7 8 9}

Who Is on the Research Team?

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06814132

NCT06814132 | A Study to Evaluate the Effect of MK-5684 ... Researchers will compare what happens to MK-5684 after hemodialysis in people with severe renal impairment and end-stage renal disease versus healthy people.

2. go.drugbank.com go.drugbank.com/conditions/DBCOND0075578

End-stage Renal Failure (ESRF) (DBCOND0075578) 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).

3. malacards.org malacards.org/card/end_stage_renal_disease

End Stage Renal Disease Integrated disease information for End Stage Renal Disease including associated genes, mutations, phenotypes, pathways, drugs, and more - integrated from 78 ...

4. reporter.nih.gov reporter.nih.gov/search/EceS1OjtPEyb06s1dmZvRw/project-details/10896266

RePORT ⟩ RePORTER We're sorry but RePORTER doesn't work properly without JavaScript enabled. Please enable it to continue.

5. merck.com merck.com/news/merck-announces-phase-3-trial-initiations-for-four-investigational-candidates-from-its-promising-hematology-and-oncology-pipeline/

Merck Announces Phase 3 Trial Initiations for Four ... Merck and Orion Corporation have initiated two pivotal Phase 3 clinical trials evaluating MK-5684 (ODM-208) in combination with hormone ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11214912/

Use of Fludrocortisone for Hyperkalemia in Chronic Kidney ... The current study shows that fludrocortisone significantly lowers serum potassium levels in pre-dialysis CKD patients and, in some cases, even results in ...

7. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK564331/

Fludrocortisone - StatPearls - NCBI Bookshelf - NIH Renal impairment: No dosage adjustments for fludrocortisone are provided in the product labeling; use with caution due to the potential for ...

8. academic.oup.com academic.oup.com/ndt/article/22/11/3273/1833626

Effect of fludrocortisone acetate on reducing serum potassium ... Several reports have shown that the potent synthetic mineralocorticoid, fludrocortisone acetate (FCA), decreased serum potassium in patients with renal ...

9. cureus.com cureus.com/articles/400929-fludrocortisone-for-refractory-hypotension-in-a-hospitalized-dialysis-patient-a-case-report

Fludrocortisone for Refractory Hypotension in a ... Initiation of fludrocortisone 0.2 mg daily resulted in significant improvement in blood pressure control and dialysis tolerance. Despite the ...