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

A Phase 1, Open-Label, Fixed-Sequence Study to Evaluate the Effects of Multiple Doses of Carbamazepine on the Single-Dose Pharmacokinetics of MK-5684 in Healthy Adult Male Participants

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Opevesostat; Drug: Prednisone; Drug: Fludrocortisone acetate; Drug: Carbamazepine

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tempe, Arizona, United States, 85283
      • Celerion ( Site 0001)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

The main inclusion criteria include but are not limited to the following:

• 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

Exclusion Criteria:

The main exclusion criteria include but are not limited to the following:

• 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)
  • Severe dermatologic reaction
  • Stomach ulcer
• Has a first-degree relative with multiple unexplained syncopal events, unexplained cardiac arrest, or sudden cardiac death, or has a known family history of an inherited arrhythmia syndrome (including Brugada syndrome)
• History of cancer (malignancy)
• Unable to refrain from or anticipates the use of: Any drugs, including prescription and non-prescription medications, herbal remedies, or vitamin supplements beginning 14 days prior to the first dosing

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Opevesostat Period 1; 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; Administered via oral tablet per dosing regimen.; Other Names: MK-5684; ODM-208; Drug: Prednisone; Administered at a dose of 5 mg or 10 mg dependent on HRT dosing regimen via oral tablets.; Other Names: RAYOS®; STERAPRED®; DELTASONE®; Drug: Fludrocortisone acetate; Administered at a dose of 0.05 mg or 0.1 mg dependent on HRT dosing regimen via oral tablets.; Other Names: FLORINEF®
Experimental: Opevesostat Period 2; 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; Administered via oral tablet per dosing regimen.; Other Names: MK-5684; ODM-208; Drug: Prednisone; Administered at a dose of 5 mg or 10 mg dependent on HRT dosing regimen via oral tablets.; Other Names: RAYOS®; STERAPRED®; DELTASONE®; Drug: Fludrocortisone acetate; Administered at a dose of 0.05 mg or 0.1 mg dependent on HRT dosing regimen via oral tablets.; Other Names: FLORINEF®; Drug: Carbamazepine; Administered at a dose of 100 mg, 200 mg, or 300 mg BID dependent on dosing regimen via oral capsule (extended-release).; Other Names: TEGRETOL®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants who experience one or more adverse events (AEs)	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who experience an AE will be determined.	Up to approximately 49 days
Number of participants who discontinue study intervention due to an AE	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who discontinue from the study due to an AE will be determined.	Up to approximately 49 days

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Investigators: Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

Helpful Links

• Merck Clinical Trials Information

Study record dates

Study Major Dates

• Study Start (Actual): December 18, 2024
• Primary Completion (Actual): February 12, 2025
• Study Completion (Actual): May 13, 2025

Study Registration Dates

• First Submitted: October 7, 2024
• First Submitted That Met QC Criteria: October 7, 2024
• First Posted (Actual): October 9, 2024

Study Record Updates

• Last Update Posted (Actual): May 25, 2025
• Last Update Submitted That Met QC Criteria: May 22, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Antineoplastic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Inflammatory Agents; Peripheral Nervous System Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Central Nervous System Depressants; Sensory System Agents; Analgesics, Non-Narcotic; Analgesics; Sodium Channel Blockers; Membrane Transport Modulators; Tranquilizing Agents; Psychotropic Drugs; Anticonvulsants; Antimanic Agents; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Prednisone; Fludrocortisone; Carbamazepine
• Other Study ID Numbers: 5684-012; MK-5684-012 (Other Identifier: MSD)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No