Drug Interaction Research Study with Opevesostat

Overseen By Toll Free Number

Age: 18 - 65

Sex: Male

Trial Phase: Phase 1

Sponsor: Merck Sharp & Dohme LLC

Must not be taking: Antifungals, Diuretics, Antipsychotics, others

Disqualifiers: Cancer, Cardiac arrhythmia, Seizures, others

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

Compensation: Varies

Number of Visits: 1

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand how the new drug, opevesostat, behaves in the body over time, specifically examining its interaction when taken alone and with carbamazepine in people with prostate cancer. In the first part, participants will take opevesostat alone, and in the second, they will take it alongside carbamazepine. The trial is suitable for non-smokers who have not used nicotine products for at least three months and can swallow multiple tablets. The goal is to advance treatment options for prostate cancer by exploring the effects of these combined medications. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new drug.

Do I need to stop my current medications for the trial?

Yes, you need to stop taking any drugs, including prescription and non-prescription medications, herbal remedies, or vitamin supplements, starting 14 days before the first dose.

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

Research has shown that opevesostat has been tested in patients with advanced prostate cancer. Early studies have assessed the drug's safety and patient tolerance. These studies found that opevesostat can block the production of certain hormones linked to prostate cancer. While the treatment has generally been well-tolerated, it is important to note that this trial is in its early stages, focusing primarily on the drug's safety for humans. Researchers are still learning about possible side effects and overall safety.

Considering joining this trial offers an opportunity to help researchers learn more about the safety of opevesostat and its interactions with other medicines like carbamazepine. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for prostate cancer?

Most treatments for hormonal deficiencies or interactions focus on providing hormone replacement therapy (HRT) alone. But opevesostat adds a unique angle by potentially altering drug interactions, especially with commonly prescribed medications like prednisone, fludrocortisone, and carbamazepine. Researchers are particularly excited about opevesostat because it may help optimize the effectiveness of HRT by addressing how these hormones interact with other drugs in the body. This could lead to more personalized and effective treatment plans for patients needing HRT.

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

Research shows that opevesostat may help treat prostate cancer, particularly in patients whose cancer resists standard hormone therapy. Studies have found that opevesostat stops the production of steroid hormones, which can aid in the growth of prostate cancer. In trials, patients with advanced prostate cancer responded well to opevesostat. This drug blocks an enzyme called CYP11A1, crucial for hormone production. Early results suggest that this method could effectively slow cancer progression. Participants in this trial will receive opevesostat in two different periods to study its interactions with other treatments. ^{1 3 5 6 7}

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 healthy adult males who haven't smoked or used nicotine products in the last 3 months. They must have a BMI between 18.0 and 32.0 kg/m2 and be able to swallow multiple tablets.

Inclusion Criteria

My BMI is between 18.0 and 32.0.

I can swallow several pills at once.

I haven't smoked or used nicotine products for at least 3 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Opevesostat Period 1

A single dose of opevesostat is administered under fasting conditions, followed by hormone replacement therapy under fed conditions

1 day

1 visit (in-person)

Washout

A washout period of at least 5 days between opevesostat dosing in Period 1 and the first carbamazepine dosing in Period 2

5 days

Opevesostat Period 2

Carbamazepine is administered twice daily for 17 days with a single dose of opevesostat on Day 14

17 days

Multiple visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Opevesostat

Trial Overview The study is testing opevesostat, a potential prostate cancer treatment, to see how it behaves in the body over time with and without carbamazepine, another medication.

How Is the Trial Designed?

Group I: Opevesostat Period 2 Experimental Treatment 4 Interventions

There will be a washout of at least 5 days between opevesostat dosing in Period 1 and the first carbamazepine dosing in Period 2. In Period 2, carbamazepine will be administered twice daily (BID) for 17 consecutive days with a single dose of opevesostat coadministered on the morning of Day 14 under fasting conditions. HRT (prednisone and fludrocortisone) will be administered under fed conditions on Day 14, approximately 4.5 hours after opevesostat and/or carbamazepine dosing.

Group II: Opevesostat Period 1 Experimental Treatment 3 Interventions

On Day 1 a single dose of opevesostat will be administered under fasting conditions and a single dose of hormone replacement therapy (HRT) (prednisone and fludrocortisone) will be administered 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

A study analyzing pharmacy claims data from 2008 to 2010 found high rates of coprescription of drugs that could potentially interact with nine enzyme-targeted kinase inhibitors, with coprescribing rates ranging from 23% to 57% depending on the specific drug.

Patients who were coprescribed these interacting drugs often had more medications overall, indicating a complex treatment regimen that may require careful monitoring to avoid decreased effectiveness or increased toxicity of the cancer treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Twelve-month frequency of drug-metabolizing enzyme and transporter-based drug-drug interaction potential in patients receiving oral enzyme-targeted kinase inhibitor antineoplastic agents. Bowlin, SJ., Xia, F., Wang, W., et al.[2021]

A review of 40 small molecular drugs approved by the FDA in 2020 revealed that oncology drugs were most affected by drug-drug interactions (DDIs), particularly through the inhibition and induction of the CYP3A enzyme, which accounted for most clinical interactions.

Three drugs—avapritinib, lonafarnib, and relugolix—were identified as sensitive substrates with very high area under the curve ratios (AUCRs) when coadministered with strong inhibitors, highlighting the importance of careful DDI management in cancer patients who often take multiple medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic Drug-Drug Interactions with Drugs Approved by the US Food and Drug Administration in 2020: Mechanistic Understanding and Clinical Recommendations. Yu, J., Wang, Y., Ragueneau-Majlessi, I.[2023]

Lexi-Interact and Drugs.com demonstrated high sensitivity (95%) in detecting drug interactions with oral antineoplastics, while Epocrates had a sensitivity of 90%, and Micromedex and Facts & Comparisons were lower at 70%.

There is a significant variation in the effectiveness of different drug interaction databases, indicating that clinicians should use multiple resources and their clinical judgment rather than relying on a single database for assessing drug interactions in oncology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug Interaction Database Sensitivity With Oral Antineoplastics: An Exploratory Analysis. Bossaer, JB., Thomas, CM.[2018]

A study combining literature review and analysis of over 800,000 patient records identified 3670 drug-drug interactions (DDIs) that could lead to increased risks of myopathy, highlighting the importance of monitoring these combinations in clinical settings.

Five specific drug pairs, including loratadine with simvastatin and promethazine with tegaserod, were found to significantly increase the risk of myopathy, suggesting that these combinations should be approached with caution due to their potential for serious adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Literature based drug interaction prediction with clinical assessment using electronic medical records: novel myopathy associated drug interactions. Duke, JD., Han, X., Wang, Z., et al.[2021]

Drug-drug interactions (DDIs) are a growing concern in modern medicine, especially as more patients with multiple health conditions (polypharmacy) take several medications, leading to an exponential increase in potential DDIs.

The article reviews both pharmacodynamic and pharmacokinetic DDIs, particularly those involving the cytochrome P450 system, and offers tools for clinicians to identify and prevent these interactions, which could ultimately reduce patient mortality and morbidity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Drug-drug interactions you should know!] Voigt, N., Ort, K., Sossalla, S.[2019]

A study analyzing 22 newly approved oral antineoplastics (OAs) found significant variability in the sensitivity and specificity of five drug-drug interaction (DDI) databases, highlighting the importance of careful DDI screening in cancer treatment.

Among the databases, Lexicomp®, Epocrates®, and Drugs.com demonstrated higher accuracy in detecting clinically relevant DDIs compared to Micromedex® and Medscape, suggesting that clinicians should choose their DDI resources wisely.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sensitivity and specificity of drug interaction databases to detect interactions with recently approved oral antineoplastics. Bossaer, JB., Eskens, D., Gardner, A.[2022]

In a study analyzing pharmacokinetic drug-drug interactions (DDIs) for 34 FDA-approved drugs in 2017, CYP3A inhibition and induction were the primary mechanisms behind most interactions, with transporters like OATP1B1/1B3 mediating about half of them.

Five new drugs were identified as sensitive substrates to interactions, and three drugs were strong inhibitors, highlighting a significant risk of DDIs, particularly in oncology and antiviral treatments where patients often take multiple medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mechanisms and Clinical Significance of Pharmacokinetic-Based Drug-Drug Interactions with Drugs Approved by the U.S. Food and Drug Administration in 2017. Yu, J., Petrie, ID., Levy, RH., et al.[2019]

Oral inhaled medications (OIMs), including bronchodilators and corticosteroids, can have clinically significant drug interactions, particularly when inhaled corticosteroids are combined with potent CYP 450 inhibitors like protease inhibitors or antifungals.

A systematic review of literature from 1980 to May 2018 highlights the importance for clinicians to be aware of these interactions to minimize adverse effects and optimize treatment for patients using OIMs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug Interactions With Oral Inhaled Medications. Ajimura, CM., Jagan, N., Morrow, LE., et al.[2021]

Camostat mesylate and its active metabolite, GBPA, do not significantly inhibit key drug transporters like P-glycoprotein and breast cancer resistance protein, suggesting a low risk for pharmacokinetic drug-drug interactions in COVID-19 patients.

The only notable interaction was with the OATP2B1 transporter, which was inhibited by GBPA at an IC50 of 11 μM, indicating that this specific interaction may require further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low risk of the TMPRSS2 inhibitor camostat mesylate and its metabolite GBPA to act as perpetrators of drug-drug interactions. Weiss, J., Bajraktari-Sylejmani, G., Haefeli, WE.[2022]

Drug-drug interactions (DDIs) are a growing concern in modern medicine, especially as more patients with multiple health conditions (polypharmacy) take several medications, leading to an exponential increase in potential DDIs.

The article reviews both pharmacodynamic and pharmacokinetic DDIs, highlighting the importance of understanding these interactions to prevent unwanted side effects and improve patient safety, particularly in an aging population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Drug-drug interactions you should know!] Voigt, N., Ort, K., Sossalla, S.[2019]

In a study of 898 ambulatory cancer patients on oral anticancer treatments, 46% experienced potential drug-drug interactions (PDDIs), with 16% having major interactions that could significantly impact their treatment.

The most common major PDDIs involved coumarins and opioids, often leading to serious effects like central nervous system issues, gastrointestinal toxicity, and prolonged QT intervals, highlighting the need for increased awareness among healthcare providers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevalence of potential drug-drug interactions in cancer patients treated with oral anticancer drugs. van Leeuwen, RW., Brundel, DH., Neef, C., et al.[2022]

Citations

1. 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.

2. aacrjournals.org aacrjournals.org/cancerres/article/85/8_Supplement_2/CT176/761812/Abstract-CT176-Pharmacokinetics-PK-of-the-novel

Pharmacokinetics (PK) of the novel nonsteroidal CYP11A1 ... We present two such PK analyses: first, opevesostat's potential drug-drug interaction (DDI) with midazolam (a sensitive CYP3A4 substrate) in a dedicated cohort.

3. urotoday.com urotoday.com/conference-highlights/esmo-2024/esmo-2024-prostate-cancer/154774-esmo-2024-opevesostat-mk-5684-odm-208-an-oral-cyp11a1-inhibitor-in-metastatic-castration-resistant-prostate-cancer-mcrpc-updated-cypides-phase-2-results.html

ESMO 2024: Opevesostat (MK-5684/ODM-208), an Oral ... Professor Karim Fizazi presented updated results of the phase II CYPIDES trial of opevesostat (ODM-208/MK-5684), an oral CYP11A1 inhibitor, in metastatic ...

4. clin.larvol.com clin.larvol.com/trial-detail/NCT03436485

Safety and Pharmacokinetics of ODM-208 in Patients ... CYPIDES phase 1 data shows that ODM-208 effectively blocked the production of all steroid hormones in men with metastatic castration-resistant prostate cancer ( ...

5. clinicaltrials.eu clinicaltrials.eu/trial/study-on-the-safety-of-odm-208-and-midazolam-for-patients-with-advanced-prostate-cancer-resistant-to-hormone-therapy/

Study of ODM-208 (opevesostat) safety and effectiveness ... This study investigates the safety and potential impact of the drug ODM-208 on metastatic castration-resistant prostate cancer, a form of ...

6. ctv.veeva.com ctv.veeva.com/study/safety-and-pharmacokinetics-of-odm-208-in-patients-with-metastatic-castration-resistant-prostate-can

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

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06353386

Study Details | NCT06353386 | Substudy 01A: Safety and ... The goal of substudy 01A is to evaluate the safety and efficacy of opevesostat-based treatment combinations, or as a single agent, in participants with mCRPC.