A Study of the Absorption, Distribution, Metabolism, and Elimination of Opevesostat (MK-5684) in Healthy Adult Male Participants (MK-5684-008)

An Open-label Phase 1 Study to Evaluate Metabolism, Excretion, and Mass Balance of [¹⁴C]MK-5684 in Healthy Male Participants

This is a study of opevesostat in healthy adult male participants. The purpose of this study is to understand the absorption, distribution, metabolism, and elimination of opevesostat in humans, as well as its pharmacokinetics (PK), metabolic profile, and safety and tolerability.

Study Overview

• Status: Completed
• Conditions: Metastatic Prostate Cancer
• Intervention / Treatment: Drug: Prednisone; Drug: [¹⁴C]Opevesostat; Drug: Fludrocortisone

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Nottinghamshire
    • Nottingham, Nottinghamshire, United Kingdom, NG11 6JS
      • Quotient Sciences ( Site 0001)

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Is a healthy male according to the assessment of the investigator
• Has a body mass index of 18.0 to 32.0 kg/m2
• Has regular bowel movements (i.e., average stool production of ≥1 and ≤3 stools per day)

Exclusion Criteria:

• Has the presence or history of clinically significant allergy requiring treatment
• Has a history of adrenal insufficiency
• Has veins not suitable for multiple venipunctures/cannulation
• Has previously taken part in more than 3 radiolabeled drug studies in the last 12 months
• Has donated blood or plasma within the previous 3 months or lost greater than 400 mL of blood

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: [¹⁴C]Opevesostat; On Day 1, participants receive a single dose of [¹⁴C]opevesostat as an oral solution. Participants then receive single doses of 5.0 mg prednisone and 0.05 mg fludrocortisone tablets 4 hours later as hormone replacement therapy.	Drug: Prednisone; Tablet; Other Names: RAYOS®; STERAPRED®; DELTASONE®; Drug: [¹⁴C]Opevesostat; Oral solution; Other Names: MK-5684; Drug: Fludrocortisone; Tablet; Other Names: FLORINEF®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative amount of total radioactivity excreted in urine (CumAeu) after administration of single-dose [¹⁴C]Opevesostat	Urine samples will be collected at pre-specified timepoints and used to determine CumAeu.	Predose and at designated time points (up to 8 days)
Cumulative amount of total radioactivity excreted in feces (CumAef) after administration of single-dose [¹⁴C]Opevesostat	Fecal samples will be collected at pre-specified timepoints and used to determine CumAef.	Predose and at designated time points (up to 8 days)
Cumulative percentage of total radioactivity excreted in urine (Cumfeu) after administration of single-dose [¹⁴C]Opevesostat	Urine samples will be collected at pre-specified timepoints and used to determine CumFeu.	Predose and at designated time points (up to 8 days)
Cumulative percentage of total radioactivity excreted in feces (Cumfef) after administration of single-dose [¹⁴C]Opevesostat	Fecal samples will be collected at pre-specified timepoints and used to determine Cumfef.	Predose and at designated time points (up to 8 days)
Plasma Opevesostat Pharmacokinetics: Area under the curve from time 0 to the time of last measurable concentration (AUC0-t)	Plasma samples will be collected at pre-specified timepoints and used to determine AUC0-t of opevesostat.	Predose and at designated time points (up to 8 days)
Plasma Opevesostat Pharmacokinetics: Area under the curve from time 0 to extrapolated infinity (AUC0-inf)	Plasma samples will be collected at pre-specified timepoints and used to determine AUC0-inf of opevesostat.	Predose and at designated time points (up to 8 days)
Plasma Opevesostat Pharmacokinetics: Maximum observed concentration (Cmax)	Plasma samples will be collected at pre-specified timepoints and used to determine Cmax of opevesostat.	Predose and at designated time points (up to 8 days)
Plasma Opevesostat Pharmacokinetics: Time of maximum observed concentration (Tmax)	Plasma samples will be collected at pre-specified timepoints and used to determine Tmax of opevesostat.	Predose and at designated time points (up to 8 days)
Plasma Opevesostat Pharmacokinetics: Terminal elimination half-life (t1/2)	Plasma samples will be collected at pre-specified timepoints and used to determine t1/2 of opevesostat.	Predose and at designated time points (up to 8 days)
Plasma Total Radioactivity Pharmacokinetics: Area under the curve from time 0 to the time of last measurable concentration (AUC0-t)	Plasma samples will be collected at pre-specified timepoints and used to determine AUC0-t of total radioactivity.	Predose and at designated time points (up to 8 days)
Plasma Total Radioactivity Pharmacokinetics: Area under the curve from time 0 to extrapolated infinity (AUC0-inf)	Plasma samples will be collected at pre-specified timepoints and used to determine AUC0-inf of total radioactivity.	Predose and at designated time points (up to 8 days)
Plasma Total Radioactivity Pharmacokinetics: Maximum observed concentration (Cmax)	Plasma samples will be collected at pre-specified timepoints and used to determine Cmax of total radioactivity.	Predose and at designated time points (up to 8 days)
Plasma Total Radioactivity Pharmacokinetics: Time of maximum observed concentration (Tmax)	Plasma samples will be collected at pre-specified timepoints and used to determine Tmax of total radioactivity.	Predose and at designated time points (up to 8 days)
Plasma Total Radioactivity Pharmacokinetics: Terminal elimination half-life (t1/2)	Plasma samples will be collected at pre-specified timepoints and used to determine t1/2 of total radioactivity.	Predose and at designated time points (up to 8 days)
Total Number of Metabolites in Plasma that Represent at least 10% of the Dose of Radioactivity	Plasma samples will be collected at pre-specified timepoints and used to determine the total number of metabolites that represent at least 10% of the dose of radioactivity. Metabolites will be determined using liquid scintillation and high-resolution mass spectrometry.	Predose and at designated time points (up to 8 days)
Total Number of Metabolites in Urine that Represent at least 10% of the Dose of Radioactivity	Urine samples will be collected at pre-specified timepoints and used to determine the total number of metabolites that represent at least 10% of the dose of radioactivity. Metabolites will be determined using liquid scintillation and high-resolution mass spectrometry.	Predose and at designated time points (up to 8 days)
Total Number of Metabolites in Feces that Represent at least 10% of the Dose of Radioactivity	Fecal samples will be collected at pre-specified timepoints and used to determine the total number of metabolites that represent at least 10% of the dose of radioactivity. Metabolites will be determined using liquid scintillation and high-resolution mass spectrometry.	Predose and at designated time points (up to 8 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with 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. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study intervention. The number of participants who experienced an AE will be reported.	Up to approximately 8 days
Number of Participants who Discontinue from the Study 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. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study intervention. The number of participants who discontinue from the study due to an AE will be reported.	Up to approximately 8 days

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Collaborators: Orion Corporation, Orion Pharma
• 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): September 19, 2024
• Primary Completion (Actual): October 17, 2024
• Study Completion (Actual): October 17, 2024

Study Registration Dates

• First Submitted: August 20, 2024
• First Submitted That Met QC Criteria: August 20, 2024
• First Posted (Actual): August 22, 2024

Study Record Updates

• Last Update Posted (Actual): October 23, 2024
• Last Update Submitted That Met QC Criteria: October 22, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Neoplasms; Antineoplastic Agents; Physiological Effects of Drugs; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Prednisone; Fludrocortisone
• Other Study ID Numbers: 5684-008; MK-5684-008 (Other Identifier: MSD); 1010197 (Registry Identifier: IRAS)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

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