A Drug-Drug Interaction Study of Carbamazepine and Opevesostat (MK-5684) in Healthy Adult Male Participants (MK-5684-012)
- Conditions
- Healthy
- Interventions
- Registration Number
- NCT06633419
- Lead Sponsor
- Merck Sharp & Dohme LLC
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 14
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
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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Opevesostat Period 1 Opevesostat 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. Opevesostat Period 2 Opevesostat 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. Opevesostat Period 1 Prednisone 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. Opevesostat Period 1 Fludrocortisone acetate 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. Opevesostat Period 2 Fludrocortisone acetate 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. Opevesostat Period 2 Prednisone 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. Opevesostat Period 2 Carbamazepine 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.
- Primary Outcome Measures
Name Time Method Area under the concentration versus time curve from 0 to infinity after single dosing (AUC0-inf) of opevesostat in plasma Predose, and at designated timepoints up to 96 hours post-dose AUC0-inf of opevesostat in plasma will be determined.
Area under the concentration versus time curve from 0 to last quantifiable sample (AUC0-last) of opevesostat in plasma Predose, and at designated timepoints up to 96 hours post-dose AUC0-last of opevesostat in plasma will be determined.
Area under the concentration versus time curve from 0 to hour 24 (AUC0-24) of opevesostat in plasma Predose, and at designated timepoints up to 24 hours post-dose AUC0-24 of opevesostat in plasma will be determined.
Maximum concentration (Cmax) of opevesostat in plasma Predose, and at designated timepoints up to 96 hours post-dose Cmax of opevesostat in plasma will be determined.
Time to Maximum concentration (Tmax) of opevesostat in plasma Predose, and at designated timepoints up to 96 hours post-dose Tmax of opevesostat in plasma will be determined.
Apparent terminal half-life (t1/2) of opevesostat in plasma Predose, and at designated timepoints up to 96 hours post-dose t1/2 of opevesostat in plasma will be determined.
Apparent Clearance (CL/F) of opevesostat in plasma Predose, and at designated timepoints up to 96 hours post-dose CL/F of opevesostat in plasma will be determined.
Apparent volume of distribution during terminal phase (Vz/F) of opevesostat in plasma Predose, and at designated timepoints up to 96 hours post-dose Vz/F of opevesostat in plasma will be determined.
- Secondary Outcome Measures
Name Time Method Number of participants who experience one or more adverse events (AEs) Up to approximately 49 days 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.
Number of participants who discontinue study intervention due to an AE Up to approximately 49 days 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.
Trial Locations
- Locations (1)
Celerion ( Site 0001)
🇺🇸Tempe, Arizona, United States