Opevesostat for Liver 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: 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand how the new medicine, opevesostat, behaves in the body over time. Researchers are testing it on both healthy individuals and those with moderate liver problems to observe any differences. Participants will take opevesostat along with a type of hormone therapy to assess its effects. Individuals with stable liver issues and signs of cirrhosis (scarring of the liver) who smoke fewer than 10 cigarettes a day may be suitable candidates. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this new treatment.

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.

Is there any evidence suggesting that opevesostat is likely to be safe for humans?

Research has shown that opevesostat is still under investigation for safety and efficacy. Early results from studies with prostate cancer patients assess the drug's tolerability by examining any side effects.

As a phase 1 trial, this is among the first tests of opevesostat in humans. The primary goal at this stage is to evaluate safety. Although specific safety data for opevesostat is not yet available, phase 1 trials are crucial for understanding a drug's behavior in the body and identifying any side effects. This information ensures the drug's safety for further testing in larger groups. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for liver disease, which typically focus on managing symptoms or slowing disease progression, opevesostat offers a new approach by potentially targeting the underlying mechanisms of the disease itself. Researchers are excited about opevesostat because it is designed to be administered orally, which could improve patient compliance compared to intravenous treatments. Additionally, the combination with hormone replacement therapy (HRT) may enhance its effectiveness, offering a dual mechanism that is not common in current liver disease treatments. This innovative strategy could lead to more efficient and effective management of liver disease symptoms.

What evidence suggests that opevesostat might be an effective treatment for prostate cancer?

Research is investigating opevesostat as a treatment for castration-resistant prostate cancer, a type of prostate cancer that grows despite very low testosterone levels. Previous studies have focused on patient survival after starting treatment. Although complete results are not yet available, early research on similar drugs has shown promise in slowing the disease. Opevesostat blocks the CYP11A1 enzyme, which is involved in producing hormones that promote prostate cancer growth. In this trial, participants with moderate hepatic impairment and healthy participants will receive opevesostat to assess its effects on liver disease. While information on the drug's impact on liver disease is limited, understanding its mechanism in the body is an important first step for broader use. ^{3 5 6 7 8}

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 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 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 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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06860243

A Study to Evaluate Opevesostat (MK-5684) in Male ... 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 ...

2. clinicaltrials.eu clinicaltrials.eu/inn/opevesostat-tosilate/

Opevesostat Tosilate – Application in Therapy and Current ... They aim to assess outcomes such as overall survival, progression-free survival, and quality of life in patients with mCRPC.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11583595/

Industry Update: the latest developments in the field of ... At least 84% of patients diagnosed with castration-resistant prostate cancer have metastatic disease at diagnosis and the disease has a ...

4. merck.com merck.com/news/merck-to-present-survival-data-and-new-research-on-10-investigational-or-approved-medicines-at-esmo-congress-2024/

Merck to Present Survival Data and New Research on 10 ... There are no data in patients with severe hepatic impairment (Child-Pugh classification C). Renal Impairment: No dosage modification is ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.TPS5114

CYP11A1 inhibitor MK-5684 versus next-generation ... Treatment will continue until unacceptable toxicity, radiographic disease progression (verified per Prostate Cancer Working Group 3 [PCWG3] ...

6. go.drugbank.com go.drugbank.com/conditions/DBCOND0166870

Hepatic Impairment (HI) (DBCOND0166870) Safety and Pharmacokinetics of Fluzoparib in Healthy Subjects and Those With Impaired Liver Function. Fluzoparib. basic_science, 1, completed. NCT06576765.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12517708/

Toxicities of novel androgen receptor pathway inhibitor ... This narrative review aims to report and discuss emergent and/or related adverse events associated with these new hormonal therapies. Recent ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT03436485

NCT03436485 | Safety and Pharmacokinetics of ODM-208 ... The purpose of this first-in-man study is to evaluate safety and tolerability of ODM-208 in patients with metastatic castration-resistant prostate cancer.