Opevesostat for Liver Disease

Recruiting at 1 trial location

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Age: 18+

Sex: Male

Trial Phase: Phase 1

Sponsor: Merck Sharp & Dohme LLC

Disqualifiers: Cancer, HIV, Hepatitis, others

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

Compensation: Varies

Number of Visits: 1

Duration: 1 day

16 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. It's best to discuss this with the trial coordinators or your doctor.

How is the drug Opevesostat unique for liver disease treatment?

Opevesostat is unique because it may target specific pathways involved in liver disease, potentially offering a novel mechanism of action compared to existing treatments like ursodeoxycholic acid or obeticholic acid, which are used for conditions like primary biliary cholangitis. While other treatments focus on reducing inflammation or improving bile flow, Opevesostat might work differently, possibly involving new targets or pathways not addressed by current therapies. ^{1 2 3 4 5}

What is the purpose of this trial?

Researchers have designed a study medicine called opevesostat as a new way to treat prostate cancer. The purpose of this study is to learn what happens to opevesostat in a person's body over time (a pharmacokinetic \[PK\] study). Researchers will compare what happens to opevesostat in the body when it is given to healthy participants and participants with moderate hepatic (liver) impairment.

Research Team

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Eligibility Criteria

This trial is for male participants with a BMI between 18.0 and 42.0 who have chronic, stable liver impairment or are healthy. They must be non-smokers or moderate smokers (≤10 cigarettes/day). It's not suitable for those outside the BMI range or with conditions that could interfere with the study.

Inclusion Criteria

The main

My BMI is between 18.0 and 42.0.

I have long-term liver disease with cirrhosis.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive a single oral dose of opevesostat and hormone replacement therapy

1 day

1 visit (in-person)

Pharmacokinetic Monitoring

Plasma samples are collected to determine pharmacokinetic parameters of opevesostat

4 days

Multiple timepoints (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

Treatment Details

Interventions

• Opevesostat

Trial Overview The study tests opevesostat to see how it's processed in the body over time, comparing its effects in healthy individuals versus those with moderate liver impairment. Fludrocortisone acetate and prednisone may also be part of the treatment regimen.

Participant Groups

Group I: Moderate Hepatic Impairment Experimental Treatment 3 Interventions

On Day 1, participants with moderate hepatic impairment will receive a single oral dose of opevesostat under fasting conditions and a single dose of hormone replacement therapy (HRT) (prednisone and fludrocortisone acetate) under fed conditions approximately 4.5 hours after opevesostat dosing. Participants with moderate hepatic impairment will receive another dose of HRT on Day 2.

Group II: Healthy Experimental Treatment 3 Interventions

On Day 1, healthy participants will receive a single oral dose of opevesostat under fasting conditions and a single dose of HRT (prednisone and fludrocortisone acetate) under fed conditions approximately 4.5 hours after opevesostat dosing.

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 the LIVIFY trial involving 120 patients with suspected fibrotic NASH, vonafexor significantly reduced liver fat content after 12 weeks, with the 100 mg and 200 mg doses showing reductions of -6.3% and -5.4% respectively, compared to -2.3% in the placebo group.

Vonafexor was found to be safe, leading to improvements in liver enzymes, body weight, and even renal function, although mild to moderate pruritus was reported in some patients, indicating manageable side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hepatic and renal improvements with FXR agonist vonafexor in individuals with suspected fibrotic NASH. Ratziu, V., Harrison, SA., Loustaud-Ratti, V., et al.[2023]

References

1. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[3rd place in the competition of scientific work in hepatology in 2010. Treatment of patients with overlap of primary biliary cirrhosis and autoimmune hepatitis]. [2015]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Primary biliary cholangitis as a roadmap for the development of novel treatments for cholestatic liver diseases†. [2023]

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

Diabetes mellitus, obesity, and hepatic steatosis. [2004]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Hepatic and renal improvements with FXR agonist vonafexor in individuals with suspected fibrotic NASH. [2023]

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

Liver histology changes in nonalcoholic steatohepatitis after one year of treatment with probucol. [2021]