A Drug-Drug Interaction Study of Carbamazepine and Opevesostat (MK-5684) in Healthy Adult Male Participants (MK-5684-012)

NCT06633419 | Completed Phase 1 FDA Drug

• 2 other identifiers: 5684-012MK-5684-012
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

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 or PK study). Researchers will compare what happens to opevesostat in the body when it is given with and without another medicine called carbamazepine.

Conditions

Healthy

Outcome Measures

Primary Outcomes (8)

• Area under the concentration versus time curve from 0 to infinity after single dosing (AUC0-inf) of opevesostat in plasma

  AUC0-inf of opevesostat in plasma will be determined.

  Predose, and at designated timepoints up to 96 hours post-dose

• Area under the concentration versus time curve from 0 to last quantifiable sample (AUC0-last) of opevesostat in plasma

  AUC0-last of opevesostat in plasma will be determined.

  Predose, and at designated timepoints up to 96 hours post-dose

• Area under the concentration versus time curve from 0 to hour 24 (AUC0-24) of opevesostat in plasma

  AUC0-24 of opevesostat in plasma will be determined.

  Predose, and at designated timepoints up to 24 hours post-dose

• Maximum concentration (Cmax) of opevesostat in plasma

  Cmax of opevesostat in plasma will be determined.

  Predose, and at designated timepoints up to 96 hours post-dose

• Time to Maximum concentration (Tmax) of opevesostat in plasma

  Tmax of opevesostat in plasma will be determined.

  Predose, and at designated timepoints up to 96 hours post-dose

• Apparent terminal half-life (t1/2) of opevesostat in plasma

  t1/2 of opevesostat in plasma will be determined.

  Predose, and at designated timepoints up to 96 hours post-dose

• Apparent Clearance (CL/F) of opevesostat in plasma

  CL/F of opevesostat in plasma will be determined.

  Predose, and at designated timepoints up to 96 hours post-dose

• Apparent volume of distribution during terminal phase (Vz/F) of opevesostat in plasma

  Vz/F of opevesostat in plasma will be determined.

  Predose, and at designated timepoints up to 96 hours post-dose

Secondary Outcomes (2)

• Number of participants who experience one or more adverse events (AEs)

  Up to approximately 49 days

• Number of participants who discontinue study intervention due to an AE

  Up to approximately 49 days

Study Arms (2)

Opevesostat Period 1

EXPERIMENTAL

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.

Drug: Opevesostat; Drug: Prednisone; Drug: Fludrocortisone acetate

Opevesostat Period 2

EXPERIMENTAL

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.

Drug: Opevesostat; Drug: Prednisone; Drug: Fludrocortisone acetate; Drug: Carbamazepine

Interventions

Opevesostat DRUG

Administered via oral tablet per dosing regimen.

Also known as: MK-5684, ODM-208

Opevesostat Period 1; Opevesostat Period 2

Prednisone DRUG

Administered at a dose of 5 mg or 10 mg dependent on HRT dosing regimen via oral tablets.

Also known as: RAYOS®, STERAPRED®, DELTASONE®

Opevesostat Period 1; Opevesostat Period 2

Fludrocortisone acetate DRUG

Administered at a dose of 0.05 mg or 0.1 mg dependent on HRT dosing regimen via oral tablets.

Also known as: FLORINEF®

Opevesostat Period 1; Opevesostat Period 2

Carbamazepine DRUG

Administered at a dose of 100 mg, 200 mg, or 300 mg BID dependent on dosing regimen via oral capsule (extended-release).

Also known as: TEGRETOL®

Opevesostat Period 2

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Continuous non-smoker who has not used nicotine- and tobacco-containing products for at least 3 months prior to the first dosing based on participant self-reporting
• Body mass index (BMI) ≥18.0 and ≤32.0 kg/m\^2
• Able to swallow multiple tablets

You may not qualify if:

• History or presence of any of the following:
• Adrenal insufficiency
• Hepatic or renal impairment
• Gallstones, hepatitis disease, or hepatic porphyrias
• Psychosis
• Clinically significant hypotension, cardiac arrhythmia, cardiac conduction abnormalities, or recurrent unexplained syncopal events
• Second- or third-degree atrioventricular heart block
• Clinically significant sick sinus syndrome
• Recurrent seizures, increased risk for seizures, or myasthenia gravis
• Clinically significant hematologic disorders/blood dyscrasias, including adverse hematologic reactions to any drugs or experimental therapies
• Any systemic fungal infection
• Chronic infection
• Glaucoma
• Hypothyroidism
• Unexplained electrolyte abnormalities, current hyponatremia, diuretic use, or syndrome of inappropriate antidiuretic hormone secretion (siADH)

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (1)

Celerion ( Site 0001)

Tempe, Arizona, 85283, United States

Location

Related Links

• Merck Clinical Trials Information

MeSH Terms

Interventions

Prednisone; fludrocortisone acetate; Carbamazepine

Intervention Hierarchy (Ancestors)

Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Dibenzazepines; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 7, 2024
• First Posted: October 9, 2024
• Study Start: December 18, 2024
• Primary Completion: February 12, 2025
• Study Completion: May 13, 2025
• Last Updated: May 25, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share

Locations

US (1)