Study of Opevesostat (MK-5684) Versus Alternative NHA in mCRPC (MK-5684-003)

A Phase 3 Randomized, Open-label Study of MK-5684 Versus Alternative Abiraterone Acetate or Enzalutamide in Participants With Metastatic Castration-resistant Prostate Cancer (mCRPC) Previously Treated With Next-generation Hormonal Agent (NHA) and Taxane-based Chemotherapy

This is a phase 3, randomized, open-label study of opevesostat compared to alternative abiraterone acetate or enzalutamide in participants with metastatic castration-resistant prostate cancer (mCRPC) with respect to overall survival (OS) and to radiographic progression-free survival (rPFS) per Prostate Cancer Working Group (PCWG) Modified Response Evaluation Criteria In Solid Tumors (RECIST 1.1) as assessed by blinded independent central review (BICR) in participants with mCRPC previously treated with next-generation hormonal agent (NHA) and taxane-based chemotherapy. It is hypothesized that opevesostat is superior with respect to OS and rPFS per PCWG Modified RECIST 1.1 as assessed by BICR in androgen receptor ligand binding domain (AR LBD) mutation-negative and -positive participants.

Study Overview

• Status: Recruiting
• Conditions: Prostate Cancer Metastatic
• Intervention / Treatment: Drug: Prednisone; Drug: Enzalutamide; Drug: Fludrocortisone acetate; Drug: Abiraterone acetate; Drug: Hydrocortisone; Drug: Dexamethasone; Drug: Opevesostat

• Study Type: Interventional
• Enrollment (Estimated): 1200
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Toll Free Number; Phone Number: 1-888-577-8839; Email: Trialsites@merck.com

Study Locations

• Australia
  • New South Wales
    • Macquarie University, New South Wales, Australia, 2109
      • Recruiting
      • Macquarie University-MQ Health Clinical Trials Unit ( Site 0234)
      • Contact: Study Coordinator; Phone Number: 0402856430
  • Victoria
    • Melbourne, Victoria, Australia, 3000
      • Recruiting
      • Peter MacCallum Cancer Centre-Parkville Cancer Clinical Trials Unit (PCCTU) ( Site 0230)
      • Contact: Study Coordinator; Phone Number: 03 8559 5000
• Canada
  • Quebec
    • Montréal, Quebec, Canada, H2X 3E4
      • Recruiting
      • Centre Hospitalier de l'Université de Montréal ( Site 0326)
      • Contact: Study Coordinator; Phone Number: 5148178779
    • Quebec City, Quebec, Canada, G1J 1Z4
      • Recruiting
      • Centre intégré de cancérologie du CHU de Québec Université Laval, Hôpital de l'Enfant-Jésus ( Site 0
      • Contact: Study Coordinator; Phone Number: 418 525-4444
    • Sherbrooke, Quebec, Canada, J1H 5H3
      • Recruiting
      • Centre intégré universitaire de santé et de services sociaux de l'Estrie - Centre Hospitalier Univer
      • Contact: Study Coordinator; Phone Number: 819-346-1110x12811
• Chile
  • Antofagasta, Chile, 1240000
    • Recruiting
    • Bradford Hill Norte ( Site 0357)
    • Contact: Study Coordinator; Phone Number: 56994198125
  • Coquimbo
    • La Serena, Coquimbo, Chile, 1720430
      • Recruiting
      • IC La Serena Research ( Site 0356)
      • Contact: Study Coordinator; Phone Number: 56993718661
  • Los Rios
    • Valdivia, Los Rios, Chile, 5110683
      • Recruiting
      • Clinical Research Chile SpA ( Site 0358)
      • Contact: Study Coordinator; Phone Number: +56940601237
  • Maule
    • Talca, Maule, Chile, 3465584
      • Recruiting
      • Clinica Universidad Catolica del Maule-Oncology ( Site 0355)
      • Contact: Study Coordinator; Phone Number: 56992992913
  • Region M. De Santiago
    • Santiago, Region M. De Santiago, Chile, 8420383
      • Recruiting
      • Bradfordhill-Clinical Area ( Site 0351)
      • Contact: Study Coordinator; Phone Number: +56954240753
    • Santiago, Region M. De Santiago, Chile, 7500921
      • Recruiting
      • FALP ( Site 0353)
      • Contact: Study Coordinator; Phone Number: +56956075934
    • Santiago, Region M. De Santiago, Chile, 8330032
      • Recruiting
      • Pontificia Universidad Catolica de Chile-Hemato-Oncology ( Site 0354)
      • Contact: Study Coordinator; Phone Number: 56223547919
• China
  • Hubei
    • Wuhan, Hubei, China, 430079
      • Recruiting
      • Hubei Cancer Hospital-Urinary surgery ( Site 0406)
      • Contact: Study Coordinator; Phone Number: 8613907110640
  • Shanghai
    • Shanghai, Shanghai, China, 200000
      • Recruiting
      • Fudan University Shanghai Cancer Center-Urology department ( Site 0376)
      • Contact: Study Coordinator; Phone Number: +86 21 64175590-1805
  • Sichuan
    • Nanchong, Sichuan, China, 637000
      • Recruiting
      • Nanchong Central Hospital-urology ( Site 0422)
      • Contact: Study Coordinator; Phone Number: 08172606822
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310014
      • Recruiting
      • Zhejiang Provincial People's Hospital-Urology ( Site 0378)
      • Contact: Study Coordinator; Phone Number: 13858019285
    • Ningbo, Zhejiang, China, 315010
      • Recruiting
      • Ningbo First Hospital-Urology ( Site 0383)
      • Contact: Study Coordinator; Phone Number: 15958800971
• Czechia
  • Brno-mesto
    • Brno, Brno-mesto, Czechia, 656 53
      • Recruiting
      • Masarykuv onkologicky ustav-Klinika komplexni onkologicke pece ( Site 0553)
      • Contact: Study Coordinator; Phone Number: 420543136216
  • Praha 5
    • Praha, Praha 5, Czechia, 150 06
      • Recruiting
      • Fakultni nemocnice v Motole-Onkologicka klinika 2. LF UK a FN Motol ( Site 0551)
      • Contact: Study Coordinator; Phone Number: 420734236410
• Finland
  • Pirkanmaa
    • Tampere, Pirkanmaa, Finland, 33520
      • Recruiting
      • Tampereen yliopistollinen sairaala ( Site 0604)
      • Contact: Study Coordinator; Phone Number: 358331166811
  • Pohjois-Savo
    • Kuopio, Pohjois-Savo, Finland, 70210
      • Recruiting
      • Kuopion Yliopistollinen Sairaala ( Site 0603)
      • Contact: Study Coordinator; Phone Number: 35817173311
  • Varsinais-Suomi
    • Turku, Varsinais-Suomi, Finland, 20520
      • Recruiting
      • Turku University Hospital-Department of Oncology ( Site 0601)
      • Contact: Study Coordinator; Phone Number: 35823130729
• France
  • Alsace
    • Strasbourg, Alsace, France, 67200
      • Recruiting
      • Institut de cancérologie Strasbourg Europe (ICANS) ( Site 0627)
      • Contact: Study Coordinator; Phone Number: 33368766767
  • Pyrenees-Atlantiques
    • Bayonne, Pyrenees-Atlantiques, France, 64109
      • Recruiting
      • Centre Hospitalier de la Côte Basque ( Site 0633)
      • Contact: Study Coordinator; Phone Number: +33559443535
• Germany
  • Berlin, Germany, 10117
    • Recruiting
    • Charité Universitaetsmedizin Berlin - Campus Mitte ( Site 0679)
    • Contact: Study Coordinator; Phone Number: 0049 30 450615297
  • Bayern
    • Munich, Bayern, Germany, 81675
      • Recruiting
      • klinikum rechts der isar der technischen universität münchen-Urologische Klinik und Poliklinik ( Sit
      • Contact: Study Coordinator; Phone Number: 498941402522
• Hong Kong
  • Hksar, Hong Kong
    • Recruiting
    • Queen Mary Hospital ( Site 0727)
    • Contact: Study Coordinator; Phone Number: 85222556220
• Israel
  • Afula, Israel, 1834111
    • Recruiting
    • Emek Medical Center ( Site 0830)
    • Contact: Study Coordinator; Phone Number: +97246495540
  • Haifa, Israel, 3109601
    • Recruiting
    • Rambam Health Care Campus-Oncology Division ( Site 0826)
    • Contact: Study Coordinator; Phone Number: 97247776750
  • Jerusalem, Israel, 9112001
    • Recruiting
    • Hadassah Medical Center ( Site 0833)
    • Contact: Study Coordinator; Phone Number: 972505172315
  • Petah Tikva, Israel, 4941 492
    • Recruiting
    • Rabin Medical Center ( Site 0828)
    • Contact: Study Coordinator; Phone Number: +972-39378074
  • Ramat Gan, Israel, 5265601
    • Recruiting
    • Sheba Medical Center ( Site 0827)
    • Contact: Study Coordinator; Phone Number: 0525505090
• Korea, Republic of
  • Seoul, Korea, Republic of, 06351
    • Recruiting
    • Samsung Medical Center ( Site 1405)
    • Contact: Study Coordinator; Phone Number: 82234101767
  • Seoul, Korea, Republic of, 03722
    • Recruiting
    • Severance Hospital, Yonsei University Health System-Medical oncology ( Site 1404)
    • Contact: Study Coordinator; Phone Number: 82222288138
  • Seoul, Korea, Republic of, 03080
    • Recruiting
    • Seoul National University Hospital-Oncology ( Site 1401)
    • Contact: Study Coordinator; Phone Number: 82220724035
  • Seoul
    • Songpagu, Seoul, Korea, Republic of, 05505
      • Recruiting
      • Asan Medical Center-Oncology ( Site 1402)
      • Contact: Study Coordinator; Phone Number: 82230106095
• Netherlands
  • Utrecht
    • Amersfoort, Utrecht, Netherlands, 3813TZ
      • Recruiting
      • Meander Medisch Centrum ( Site 1157)
      • Contact: Study Coordinator; Phone Number: 31338501189
• Norway
  • Akershus
    • Lørenskog, Akershus, Norway, 1474
      • Recruiting
      • Akershus Universitetssykehus-Onkologisk avdeling ( Site 1227)
      • Contact: Study Coordinator; Phone Number: 004793299618
  • Ostfold
    • Sarpsborg, Ostfold, Norway, 1714
      • Recruiting
      • Sykehuset Østfold Kalnes ( Site 1228)
      • Contact: Study Coordinator; Phone Number: 4791508600
  • Sor-Trondelag
    • Trondheim, Sor-Trondelag, Norway, 7030
      • Recruiting
      • St. Olavs Hospital-Kreftklinikken ( Site 1231)
      • Contact: Study Coordinator; Phone Number: 47 72 82 61 66
• Poland
  • Mazowieckie
    • Siedlce, Mazowieckie, Poland, 08-110
      • Recruiting
      • Mazowiecki Szpital Wojewódzki w Siedlcach-Siedleckie Centrum Onkologii ( Site 1310)
      • Contact: Study Coordinator; Phone Number: 48698826497
• Puerto Rico
  • Ponce, Puerto Rico, 00717
    • Recruiting
    • Ad-Vance Medical Research-Research ( Site 1353)
    • Contact: Study Coordinator; Phone Number: 7876516697
  • San Juan, Puerto Rico, 00909
    • Recruiting
    • Pan American Center for Oncology Trials - Ciudadela ( Site 1351)
    • Contact: Study Coordinator; Phone Number: 7876745868
• Spain
  • Lugo, Spain, 27003
    • Recruiting
    • Hospital Lucus Augusti-Oncology ( Site 1432)
    • Contact: Study Coordinator; Phone Number: 34982296459
  • Sevilla, Spain, 41013
    • Recruiting
    • HOSPITAL UNIVERSITARIO VIRGEN DEL ROCIO-Medical Oncology ( Site 1428)
    • Contact: Study Coordinator; Phone Number: 34955013068
  • Madrid, Comunidad De
    • Madrid, Madrid, Comunidad De, Spain, 28034
      • Recruiting
      • Hospital Universitario Ramón y Cajal-Medical Oncology ( Site 1431)
      • Contact: Study Coordinator; Phone Number: 34913368263
    • Madrid, Madrid, Comunidad De, Spain, 28041
      • Recruiting
      • Hospital Universitario 12 de Octubre-Medical Oncology ( Site 1433)
      • Contact: Study Coordinator; Phone Number: 349683609003807
• Sweden
  • Uppsala Lan
    • Uppsala, Uppsala Lan, Sweden, 751 85
      • Recruiting
      • Akademiska sjukhuset-Blod- och tumörsjukdomar ( Site 1477)
      • Contact: Study Coordinator; Phone Number: +46736869248
• Taiwan
  • Taichung, Taiwan, 40447
    • Recruiting
    • China Medical University Hospital-Department of Urology ( Site 1503)
    • Contact: Study Coordinator; Phone Number: 886-975-681295
  • Taipei, Taiwan, 100225
    • Recruiting
    • National Taiwan University Hospital-Urology ( Site 1506)
    • Contact: Study Coordinator; Phone Number: 88622312345665238
  • Taipei, Taiwan, 112
    • Recruiting
    • Taipei Veterans General Hospital ( Site 1505)
    • Contact: Study Coordinator; Phone Number: 886228757519304
• Turkey
  • Ankara, Turkey, 06230
    • Recruiting
    • Hacettepe Universite Hastaneleri-oncology hospital ( Site 1551)
    • Contact: Study Coordinator; Phone Number: +905334318506
  • Ankara, Turkey, 06520
    • Recruiting
    • Memorial Ankara Hastanesi-Medical Oncology ( Site 1557)
    • Contact: Study Coordinator; Phone Number: 903122536666
• United States
  • Colorado
    • Lakewood, Colorado, United States, 80228
      • Recruiting
      • Colorado Clinical Research ( Site 0067)
      • Contact: Study Coordinator; Phone Number: 303-885-9828
  • Nevada
    • Las Vegas, Nevada, United States, 89148
      • Recruiting
      • Comprehensive Cancer Centers of Nevada ( Site 0010)
      • Contact: Study Coordinator; Phone Number: 702-952-1251
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Recruiting
      • University Hospitals Cleveland Medical Center ( Site 0043)
      • Contact: Study Coordinator; Phone Number: 216-844-3951
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • Recruiting
      • University of Virginia Health System ( Site 0054)
      • Contact: Study Coordinator; Phone Number: 434-327-3029
    • Roanoke, Virginia, United States, 24014
      • Recruiting
      • Blue Ridge Cancer Care ( Site 0004)
      • Contact: Study Coordinator; Phone Number: 540-982-0237

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Has histologically- or cytologically-confirmed adenocarcinoma of the prostate without small cell histology
• Has prostate cancer progression while on androgen deprivation therapy (or post bilateral orchiectomy) within 6 months before Screening
• Has current evidence of metastatic disease documented by either bone lesions on bone scan and/or soft tissue disease by computed tomography/magnetic resonance imaging (CT/MRI)
• Has disease that progressed during or after treatment with 1 novel hormonal agent (NHA)
• Has received 1 but no more than 2 taxane-based chemotherapy regimens for metastatic castration-resistant prostate cancer (mCRPC) and has had progressive disease (PD) during or after treatment
• Has ongoing androgen deprivation with serum testosterone <50 ng/dL (<1.7 nM)
• Has provided tumor tissue from a fresh core or excisional biopsy from soft tissue not previously irradiated
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 assessed within 7 days of randomization
• Has had prior treatment with PARPi or were deemed ineligible to receive treatment by the investigator or have refused PARPi treatment
• Has received prior 177Lu-PSMA-617 or were deemed ineligible to receive 177Lu-PSMA-617 treatment by the investigator or refused 177Lu-PSMA-617 treatment
• Participants who have not received cabazitaxel can be enrolled if they are ineligible for cabazitaxel treatment as determined by the investigator or have refused treatment
• If participant received first generation anti-androgen therapy before screening, the participant has evidence of disease progression >4 weeks since the last flutamide treatment and >6 weeks since the last bicalutamide or nilutamide treatment
• Participants receiving bone resorptive therapy (including, but not limited to, bisphosphonate or denosumab) must have been on stable doses for ≥ 4 weeks before the date of randomization
• Participants with human immunodeficiency virus (HIV) infection must have well controlled HIV on antiretroviral therapy (ART)
• Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and have undetectable HBV viral load before randomization
• Participants with history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at Screening.
• Participants who can produce sperm must agree to the following during the study treatment period and for at least 7 days after the last dose of opevesostat, for at least 30 days after the last dose of abiraterone acetate, and for at least 3 months after the last dose of enzalutamide: EITHER be abstinent OR must agree to use male condom

Exclusion Criteria:

• Has a gastrointestinal disorder that might affect absorption
• Has a history of pituitary dysfunction
• Has poorly controlled diabetes mellitus
• Has clinically significant abnormal serum potassium or sodium level
• Has a history of active or unstable cardio/cerebro-vascular disease, including thromboembolic events
• Has a history of seizure within 6 months of providing documented informed consent or any condition that may predispose to seizures within 12 months before the date of randomization
• Has a history of clinically significant ventricular arrhythmias
• Has received an anticancer monoclonal antibody (mAb) within 4 weeks before the date of randomization, or has not recovered from adverse events (AEs) due to mAbs administered more than 4 weeks before the date of randomization
• Has undergone major surgery, including local prostate intervention (except prostate biopsy), within 28 days before the date of randomization, and has not recovered from the toxicities and/or complications
• Participants who have not adequately recovered from major surgery or have ongoing surgical complications
• Has used herbal or medicinal products that may have hormonal anti-prostate cancer activity and/or are known to decrease prostate-specific Antigen (PSA) (eg, saw palmetto, megesterol acetate) within 4 weeks before the date of randomization
• Has received radium-223 or lutetium-177 within 4 weeks before the date of randomization, or has not recovered to Grade ≤1 or baseline from AEs due to radium-223 or lutetium-177 administered more than 4 weeks before the date of randomization
• Has received treatment with 5-αreductase inhibitors (eg, finasteride or dutasteride), estrogens, or cyproterone within 4 weeks before the date of randomization
• Has received colony-stimulating factors within 28 days before the date of randomization
• Has received a whole blood transfusion in the last 120 days before the date of randomization. Packed red blood cells and platelet transfusions are acceptable if not given within 28 days of the date of randomization
• Has received prior targeted small molecule therapy or NHA treatment within 4 weeks before the first dose of study intervention as follows: enzalutamide or apalutamide within 3 weeks or abiraterone acetate + prednisone or darolutamide within 2 weeks
• Has a "superscan" bone scan
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior the first dose of study medication
• Has a known additional malignancy that is progressing or has required active treatment within the past 3 years
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
• Has an active autoimmune disease that has required systemic treatment in past 2 years
• Has an active infection requiring systemic therapy
• Has concurrent active HBV or known active HCV infection
• Has a history of long QTc syndrome
• Has any of the following at Screening Visit: hypotension (systolic BP <110 mm Hg) or uncontrolled hypertension (systolic BP ≥160 mm Hg or diastolic BP ≥90 mm Hg, in 2 out of 3 recordings with optimized antihypertensive therapy)
• Is unable to swallow capsules/tablets
• Is currently being treated with cytochrome 450-inducing antiepileptic drugs for seizures
• Participants on an unstable dose of thyroid hormone therapy within 6 months before the start of the study intervention
• Received prior systemic anticancer therapy including investigational agents within 4 weeks before the first dose of study intervention
• Received prior radiotherapy within 2 weeks of start of study intervention, or radiation-related toxicities, requiring corticosteroids
• Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention
• Systemic use of the following medications within 2 weeks before the first dose of study intervention: strong CYP3A4 inducers (eg, avasimibe, carbamazepine, lumacaftor, phenobarbital, rifampicin, rifapentine, or St John's Wort); P-gp inhibitors (eg, erythromycin, clarithromycin, rifampicin, ketoconazole, itraconazole, posaconazole, artesunate-pyronaridine, ritonavir, indinavir, nelfinavir, atazanavir, glecaprevir-pibrentasvir, simeprevir, ledipasvir-sofosbuvir, verapamil, diltiazem, dronedarone, propafenone, quinidine, cyclosporine, valspodar, or milk thistle [Silybum marianum])
• Use of aldosterone antagonist (eg, spironolactone, eplerenone) and phenytoin within 4 weeks before the start of the study intervention

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Abiraterone Acetate or Enzalutamide; Participants receive abiraterone 1000 mg qd by oral tablets plus prednisone 5 mg bid by oral tablets or enzalutamide 160 mg qd by oral tablets.	Drug: Prednisone; Administered orally; Drug: Enzalutamide; Administered orally; Other Names: XTANDI; Drug: Abiraterone acetate; Administered orally; Other Names: ZYTIGA; YONSA
Experimental: Opevesostat; Participants receive opevesostat 5 mg by oral tablets twice daily (bid) plus dexamethasone 1.5 mg by oral tablets once daily (qd) and 0.1 mg fludrocortisone acetate by oral tablet qd until progression. Hydrocortisone 100 mg (oral or intramuscular [IM]) dose will also be provided to participants for use as rescue medication.	Drug: Fludrocortisone acetate; Administered orally; Drug: Hydrocortisone; Administered orally or IM as a rescue medication; Drug: Dexamethasone; Administered orally as rescue medication; Drug: Opevesostat; Administered orally; Other Names: MK-5684

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS) in Androgen Receptor Ligand Binding Domain (AR LBD) Mutation-Positive Participants	OS is defined as time from randomization to death due to any cause. OS in AR LBD mutation-positive participants will be reported for each study arm.	Up to ~54 months
OS in AR LBD Mutation-Negative Participants	OS is defined as time from randomization to death due to any cause. OS in AR LBD mutation-negative participants will be reported for each study arm.	Up to ~54 months
Radiographic Progression-free Survival (rPFS) Per Prostate Cancer Working Group-modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review in AR LBD Mutation-Positive Participant	rPFS is defined as the time from randomization to the first documented disease progression per Prostate Cancer Working Group (PCWG)-modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as assessed by Blinded Independent Central Review (BICR) or death due to any cause, whichever occurs first. rPFS in AR LBD mutation-positive participants will be reported for each study arm.	Up to ~36 months
rPFS Per Prostate Cancer Working Group-modified RECIST 1.1 as Assessed by Blinded Independent Central Review in AR LBD Mutation-Negative Participants	rPFS is defined as the time from randomization to the first documented disease progression per PCWG-modified RECIST 1.1 as assessed by BICR or death due to any cause, whichever occurs first. rPFS in AR LBD mutation-negative participants will be reported for each study arm.	Up to ~36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Initiation of the First Subsequent Anti-Cancer Therapy or Death (TFST)	TFST is defined as the time from randomization to initiation of the first subsequent anticancer therapy or death, whichever occurs first.	Up to ~54 months
Objective Response (OR)	OR is determined by PCWG-modified RECIST 1.1 as assessed by BICR.	Up to ~54 months
Duration of Response (DOR)	DOR is determined by PCWG-modified RECIST 1.1 as assessed by BICR.	Up to ~54 months
Time to Pain Progression (TTPP)	TTPP is assessed by Brief Pain Inventory-Short Form (BPI-SF) Item 3 ("Worst Pain in 24 Hours") and opiate analgesic use (Analgesic Quantification Algorithm [AQA] Score).	Up to ~54 months
Time to Prostate-specific Antigen (PSA) Progression	The time from randomization to PSA progression. The PSA progression date is defined as the date of either: 1) ≥25% increase and ≥2 ng/mL above the nadir, confirmed by a second value ≥3 weeks later if there is PSA decline from baseline 2) ≥25% increase and ≥2 ng/mL increase from baseline beyond 12 weeks if there is no PSA decline from baseline.	Up to ~54 months
Time to First Symptomatic Skeletal-related Event (SSRE)	The time from randomization to the first occurrence of any of the following symptomatic skeletal-related events: 1) Use of EBRT to prevent or relieve skeletal symptoms; 2) new symptomatic pathologic bone fracture (vertebral or nonvertebral); 3) spinal cord compression; or 4) tumor-related orthopedic surgical intervention.	Up to ~54 months
Number of Participants Who Experience an Adverse Event	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.	Up to ~54 months
Number of Participants Who Discontinue Study Treatment Due to an Adverse Event	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.	Up to ~54 months

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): December 31, 2023
• Primary Completion (Estimated): August 2, 2028
• Study Completion (Estimated): August 2, 2028

Study Registration Dates

• First Submitted: November 13, 2023
• First Submitted That Met QC Criteria: November 13, 2023
• First Posted (Actual): November 18, 2023

Study Record Updates

• Last Update Posted (Estimated): April 26, 2024
• Last Update Submitted That Met QC Criteria: April 25, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Steroid Synthesis Inhibitors; Dexamethasone; Prednisone; Abiraterone Acetate; Hydrocortisone; Fludrocortisone
• Other Study ID Numbers: 5684-003; 2023-504899-25 (Other Identifier: EU CT); MK-5684-003 (Other Identifier: Merck); jRCT2031240029 (Registry Identifier: Japan Registry of Clinical Trials (jRCT))

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