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

Merck Sharp & Dohme (MSD)

Status and phase: Active, not recruiting; Phase 1

Conditions: Healthy

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT06633419

5684-012

MK-5684-012 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 14 estimated patients

Sex: Male

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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14 participants in 2 patient groups

Opevesostat Period 1

Experimental group

Description:

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.

Treatment:

Drug: Prednisone

Drug: Fludrocortisone acetate

Drug: Opevesostat

Opevesostat Period 2

Experimental group

Description:

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.

Treatment:

Drug: Prednisone

Drug: Fludrocortisone acetate

Drug: Opevesostat

Drug: Carbamazepine