Safety and Efficacy Study of Enzalutamide Plus Leuprolide in Patients With Nonmetastatic Prostate Cancer (EMBARK)

Prostate Cancer Clinical Trial

Official title:

A Phase 3, Randomized, Efficacy and Safety Study of Enzalutamide Plus Leuprolide, Enzalutamide Monotherapy, and Placebo Plus Leuprolide in Men With High-Risk Nonmetastatic Prostate Cancer Progressing After Definitive Therapy

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02319837
• Other study ID #: MDV3100-13
• Secondary ID: C34310042014-001
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: December 17, 2014
• Est. completion date: September 19, 2026

Study information

• Verified date: March 2024
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to assess enzalutamide plus leuprolide in patients with high-risk nonmetastatic prostate cancer progressing after radical prostatectomy or radiotherapy or both.

The randomized / blinded portion of the study is now completed following primary endpoint analyses. The study remains ongoing in open label format.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1068
• Est. completion date: September 19, 2026
• Est. primary completion date: January 31, 2023
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically or cytologically confirmed adenocarcinoma of the prostate at initial biopsy, without neuroendocrine differentiation, signet cell, or small cell features;

• Prostate cancer initially treated by radical prostatectomy or radiotherapy (including brachytherapy) or both, with curative intent;

• PSA doubling time = 9 months;

• Screening PSA by the central laboratory = 1 ng/mL for patients who had radical prostatectomy (with or without radiotherapy) as primary treatment for prostate cancer and at least 2 ng/mL above the nadir for patients who had radiotherapy only as primary treatment for prostate cancer;

• Serum testosterone = 150 ng/dL (5.2 nmol/L).

Exclusion Criteria:

• Prior or present evidence of distant metastatic disease as assessed by radiographic imaging;

• Prior hormonal therapy. Neoadjuvant/adjuvant therapy to treat prostate cancer = 36 months in duration and = 9 months before randomization, or a single dose or a short course (= 6 months) of hormonal therapy given for rising PSA = 9 months before randomization is allowed.;

• Prior cytotoxic chemotherapy, aminoglutethimide, ketoconazole, abiraterone acetate, or enzalutamide for prostate cancer;

• Prior systemic biologic therapy, including immunotherapy, for prostate cancer;

• Major surgery within 4 weeks before randomization;

• Treatment with 5-a reductase inhibitors (finasteride, dutasteride) within 4 weeks of randomization;

• Known or suspected brain metastasis or active leptomeningeal disease;

• History of another invasive cancer within 3 years before screening, with the exception of fully treated cancers with a remote probability of recurrence

Related Conditions & MeSH terms

• Cancer of the Prostate
• Hormone Sensitive Prostate Cancer
• Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• Enzalutamide

• Placebo (No longer applicable in Open Label study period)
Sugar pill to mimic enzalutamide
• Leuprolide Open Label

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Icon Cancer Care Wesley	Auchenflower	Queensland
Australia	Box Hill Hospital	Box Hill	Victoria
Australia	Icon Cancer Care Chermside	Chermside	Queensland
Australia	Monash Medical Centre	Clayton	Victoria
Australia	Genesis Cancer Care NSW	Gateshead	New South Wales
Australia	Austin Health	Heidelberg	Victoria
Australia	Lismore Base hospital	Lismore	New South Wales
Australia	Liverpool Hospital	Liverpool	New South Wales
Australia	Australian Urology Associates	Malvern	Victoria
Australia	Fiona Stanley Hospital	Murdoch	Western Australia
Australia	Macquarie University	North Ryde	New South Wales
Australia	Genesis Cancer Care	North Sydney	New South Wales
Australia	Port Macquarie Base Hospital	Port Macquarie	New South Wales
Australia	Icon Cancer Care South Brisbane	South Brisbane	Queensland
Australia	Icon Cancer Foundation	South Brisbane	Queensland
Australia	Icon Cancer Centre Southport	Southport	Queensland
Australia	Sunshine Hospital	St Albans	Victoria
Australia	GenesisCare North Shore	St Leonards	New South Wales
Australia	The Tweed Hospital	Tweed Heads	New South Wales
Australia	Australian Clinical Trials Pty Ltd	Wahroonga	New South Wales
Australia	Sydney Adventist Hospital	Wahroonga	New South Wales
Australia	Calvary Mater Newcastle	Waratah	New South Wales
Australia	Crown Princess Mary Cancer Centre	Westmead	NEW
Australia	Westmead Hospital	Westmead	New South Wales
Australia	Illawarra Cancer Care Centre	Wollongong	New South Wales
Austria	Hospital Barmherzige Schwestern Linz	Linz	Upper Austria
Austria	Hospital Barmherzige Schwestern Linz, Department of Urology	Linz
Austria	Ordensklinikum Linz GmbH	Linz
Austria	Department of Nuclear Medicine and Endocrinology, University Hospital Salzburg, Austria	Salzburg
Austria	Department of Radiology, University Hospital Salzburg, Austria	Salzburg
Austria	Department of Urology,Paracelsus Medical University Salzburg	Salzburg
Austria	AKH - Medizinische Universität Wien	Vienna
Austria	Department of Internal Medicine I, Medical university Vienna	Vienna
Brazil	Fundacao Pio XII - Hospital de Cancer de Barretos	Barretos	SP
Brazil	Hospital das Clinicas da Faculdade de Ciencias Medicas da UNICAMP	Campinas	SP
Brazil	Liga Paranaense de Combate ao Cancer - Hospital Erasto Gaertner	Curitiba	Parana
Brazil	Oncosite - Centro de Pesquisa Clinica em Oncologia Ltda	Ijuí/RS
Brazil	CITO - Centro Integrado de Terapia Onco-Hematologica - Hospital de Clinicas de Passo Fundo	Passo Fundo	RS
Brazil	CLINIONCO - Clinica de Oncologia de Porto Alegre Ltda.	Porto Alegre	RS
Brazil	Hospital de Clinicas de Porto Alegre	Porto Alegre	RS
Brazil	Hospital Sao Lucas da PUCRS	Porto Alegre	RS
Brazil	Hospital São Rafael S.A	Salvador	BA
Brazil	Centro de Estudos e Pesquisas de Hematologia e Oncologia - Faculdade de Medicina do ABC	Santo Andre	SP
Canada	The Male/Female Health and Research Centre, Royal Court Medical Centre	Barrie	Ontario
Canada	Prostate Cancer Centre	Calgary	Alberta
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	Urology South Shore Research	Greenfield Park	Quebec
Canada	Nova Scotia Health Authority	Halifax	Nova Scotia
Canada	Centre for Applied Urological Research	Kingston	Ontario
Canada	Hotel Dieu Hospital	Kingston	Ontario
Canada	Kingston General Hospital	Kingston	Ontario
Canada	Urology Associates/ Urologic Medical Research	Kitchener	Ontario
Canada	London Health Sciences Centre - Victoria Hospital	London	Ontario
Canada	Centre Hospitalier de l'Universite de Montreal	Montreal	Quebec
Canada	McGill University Health Centre	Montreal	Quebec
Canada	Ultra-Med Inc.	Pointe-Claire	Quebec
Canada	CHU de Quebec - L'Hotel-Dieu de Quebec	Quebec
Canada	CHU de Quebec - L'Hotel-Dieu de Quebec - CRCEO	Quebec
Canada	Sunnybrook Health Sciences Centre	Toronto	Ontario
Canada	University Health Network - Princess Margaret Cancer Centre	Toronto	Ontario
Canada	Vancouver Prostate Centre	Vancouver	British Columbia
Canada	Manitoba Prostate Centre CancerCare Manitoba	Winnipeg	Manitoba
Denmark	Aarhus University Hospital	Arhus N
Denmark	Rigshospitalet - Copenhagen University Hospital	Copenhagen
Denmark	Rigshospitalet, Dept of Radiology	Copenhagen
Denmark	Rigshospitalet - Copenhagen University Hospital	Copenhagen N
Denmark	Odense University Hospital	Odense C
Denmark	Vejle Sygehus	Vejle
Finland	Helsingin yliopistollinen keskussairaala	Helsinki
Finland	Oulun yliopistollinen sairaala	Oulu
Finland	Satakunnan Keskussairaala	Pori
Finland	Seinaejoen Keskussairaala	Seinaejoki
Finland	Tampereen yliopistollinen sairaala	Tampere
France	ICO- site Paul Papin	Angers cedex 09
France	Clinique Pasteur - Lanroze	Brest
France	Clinique Pasteur - Lanroze Service Pharmacie	Brest
France	CHD Vendée	LA ROCHE SUR YON cedex 9
France	CHRU de Lille - Hopital Claude Huriez	Lille cedex
France	ICM Val d'Aurelle	Montpellier Cedex 5
France	CHU de Nantes - Hotel Dieu	Nantes
France	Hopital Saint-Louis	Paris cedex 10
France	Institut Mutualiste Montsouris	Paris Cedex 14
France	CHP Saint-Gregoire	Saint-Gregoire
France	ICO - site Rene Gauducheau	Saint-Herblain cedex
France	Hia Begin	Saint-Mande
France	Hopital Foch	Suresnes
France	Institut Gustave Roussy	Villejuif
France	Institut Gustave Roussy	Villejuif cedex
Italy	Farmacia, Azienda Socio Sanitaria Territoriale di Cremona	Cremona
Italy	Struttura Complessa di Oncologia, Azienda Socio Sanitaria Territoriale di Cremona	Cremona
Italy	UO di Radiologia, Azienda Socio Sanitaria Territoriale di Cremona	Cremona
Italy	UO di Oncologia,Ospedale Civile degli Infermi	Faenza RA
Italy	UO di Radiologia, Ospedale Civile degli Infermi	Faenza RA
Italy	UO di Oncologia, Ospedale Civile Umberto I	Lugo RA
Italy	Uo di Radiologia, Ospedale Civile Umberto I	Lugo RA
Italy	Laboratorio Farmaci Antiblastici, IRCCS Istituto	Meldola (FC)
Italy	U.O. Oncologia Medica, IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori	Meldola (FC)
Italy	UO Radiologia,IRCCS Istituto Scientifico Romagnolo Per lO Studio e la Cura dei Tumori (IRST)	Meldola (FC)
Italy	Istituto Nazionale Tumori Fondazione G. Pascale/Oncologia Medica A	Napoli
Italy	S.C.D.U. Oncologia Medica, A.O.U. San Luigi Gonzaga	Orbassano (TO)
Italy	S.C.D.U. Radiodiagnostica, A.O.U. San Luigi Gonzaga	Orbassano (TO)
Italy	Servizio di Farmacia, Ospedale Santa Maria delle Croci	Ravenna
Italy	Servizio di Radiologia, Ospedale Santa Maria Delle Croci	Ravenna
Italy	UO di Oncologia Medica, Ospedale Santa Maria delle Croci	Ravenna
Italy	Farmacia Interna, Ospedale degli Infermi	Rimini
Italy	UO Oncologia, Ospedale degli Infermi	Rimini
Italy	Azienda Ospedaliera S, Camillo Forlanini, UOC per il governo clinico in Oncologia Medica,pad,Flajani	Roma
Italy	U.O. di Oncologia Medica, Ospedale Santa Chiara	Trento
Italy	U.O. Medicina Nucleare, Ospedale Santa Chiara	Trento
Italy	U.O. Radiologia, Ospedale Santa Chiara	Trento
Korea, Republic of	Chonnam National University Hwasun Hospital	Hwasun-gun	Jeollanam-do
Korea, Republic of	Gachon University Gil Medical Center	Incheon
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si	Gyeonggi-do
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Gangnam Severance Hospital, Yonsei University Health System	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Severance Hospital. Yonsei University Health System	Seoul
Korea, Republic of	Pusan National University Yangsan Hospital	Yangsan-si	Gyeongsangnam-do
Netherlands	Academisch Medisch Centrum	Amsterdam
Netherlands	VU Medical Centrum, Department of Urology	Amsterdam
Netherlands	Gelderse Vallei Ziekenhuis	Ede
Netherlands	Catharina Ziekenhuis Eindhoven	Eindhoven
Netherlands	University Medical Centrum Groningen, Department Urologie	Groningen
Netherlands	Medisch Centrum Leeuwarden	Leeuwarden
Netherlands	Maastricht University Medical Center, Department of Urology	Maastricht
Netherlands	Antonius Ziekenhuis	Sneek
Poland	Uniwersyteckie Centrum Kliniczne Klinika Onkologii i Radioterapii	Gdansk
Poland	Wojewodzki Szpital Specjalistyczny im. Janusza Korczaka w Slupsku Sp. z o. o.	Slupsk
Poland	Wojewodzki Szpital Specjalistyczny im. Janusza Korczaka w Slupsku Sp. z o.o., Oddzial Urologiczny	Slupsk
Poland	Kujawsko-Pomorskie Centrum Urologicznw Sp z o.o	Torun
Poland	Centrum Medyczne Melita Medical	Wroclaw
Poland	EMC Instytut Medyczny Spolka Akcyjna	Wroclaw
Slovakia	Fakultna nemocnica s poliklinikou F.D.Roosevelta	Banska Bystrica
Slovakia	CUIMED, s.r.o., Urologicka ambulancia	Bratislava
Slovakia	Vychodoslovensky onkologicky ustav, a.s.	Kosice
Slovakia	Univerzitna nemocnica Martin	Martin
Slovakia	UROEXAM, spol. s r.o.	Nitra
Slovakia	MILAB	Presov
Slovakia	Fakultna nemocnica s poliklinikou Zilina	Zilina
Spain	Hospital Clinic i Provincial de Barcelona, Dr. Antonio Alcaraz Asensio	Barcelona
Spain	Hospital del Mar	Barcelona
Spain	Hospital Universitario Puerta del Mar	Cadiz
Spain	ICO Girona; Hospital Universitari de Girona Dr. Josep Trueta. Servicio de Oncologia	Girona
Spain	Centro Oncologico MD Anderson International Espana	Madrid
Spain	Hospital General Universitario Gregorio Maranon. Servicio de Oncologia.	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario de La Princesa	Madrid
Spain	Hospital Universitario Ramon Y Cajal	Madrid
Spain	Althaia, Xarxa Assistencial Universitària de Manresa	Manresa
Spain	Althaia, Xarxa Assistencial Universitària de Manresa	Manresa	Barcelona
Spain	Complejo Hospitalario Universitario de Orense	Orense
Spain	Hospital Universitari Son Espases	Palma de Mallorca	Islas Baleares
Spain	Corporacio Sanitaria Parc Tauli	Sabadell
Spain	Hospital Clinico Universitario de Salamanca	Salamanca
Spain	Complejo Hospitalario Universitario de Santiago	Santiago de Compostela	LA Coruna
Spain	Instituto Valenciano de Oncologia IVO	Valencia
Sweden	Sahlgrenska Universitetssjukhuset, Sahlgrenska	Goteborg
Sweden	Skanes Universitetssjukhus	Malmo
Sweden	Universitetssjukhuset Orebro	Orebro
Sweden	Karolinska Universitetssjukhuset Solna	Stockholm
Sweden	Sodersjukhuset AB	Stockholm
Sweden	Norrlands Universitetssjukhus	Umea
Sweden	Norrlands Universitetssjukhus	Umea
Sweden	Akademiska Sjukhuset	Uppsala
Taiwan	Kaohsiung Medical University Chung-Ho Memorial Hospital	Kaohsiung
Taiwan	China Medical University Hospital	Taichung
Taiwan	Taichung Veterans General Hospital	Taichung
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Chang Gung Memorial Hospital, Linkou	Taoyuan
United Kingdom	Cancer Centre, Queen Elizabeth Hospital	Birmingham	WEST Midlands
United Kingdom	University Hospitals Bristol NHS Foundation Trust	Bristol
United Kingdom	Beatson West of Scotland Cancer Centre	Glasgow
United Kingdom	Ross Hall Hospital	Glasgow	CITY OF Glasgow
United Kingdom	Royal Free Hospital	London	Greater London
United Kingdom	The Royal Marsden NHS Foundation Trust	Sutton	Surrey
United Kingdom	Royal Devon & Exeter Hospital	Wonford, Exeter	Devon
United States	Alaska Urological Institute dba Alaska Clinical Research Center	Anchorage	Alaska
United States	Emory University Hospital	Atlanta	Georgia
United States	Investigational Drug Service	Atlanta	Georgia
United States	The Emory Clinic	Atlanta	Georgia
United States	Winship Cancer Institute, Emory University	Atlanta	Georgia
United States	Urologic Consultants of SE PA	Bala-Cynwyd	Pennsylvania
United States	John Hopkins University Hospital	Baltimore	Maryland
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland
United States	The Sidney Kimmel Cancer Center at Johns Hopkins Hospital- Oncology Investigational Drug Services	Baltimore	Maryland
United States	Memorial Sloan Kettering Cancer Center Basking Ridge	Basking Ridge	New Jersey
United States	Tower Hematology Oncology Medical Group	Beverly Hills	California
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	University of Alabama at Birmingham, IDS Pharmacy	Birmingham	Alabama
United States	Northwestern Medical Group	Chicago	Illinois
United States	Northwestern Memorial Hospital	Chicago	Illinois
United States	Mercy Health Jewish Hospital	Cincinnati	Ohio
United States	TriState Urologic Services PSC Inc., dba The Urology Group	Cincinnati	Ohio
United States	Memorial Sloan Kettering Cancer Center Commack	Commack	New York
United States	Urology Clinics of North Texas, PLLC	Dallas	Texas
United States	The Urology Center of Colorado	Denver	Colorado
United States	Duke Investigational Chemotherapy Services	Durham	North Carolina
United States	Duke Nuclear Medicine	Durham	North Carolina
United States	Duke University Medical Center	Durham	North Carolina
United States	Oregon Imaging Center	Eugene	Oregon
United States	VA Lahontan Valley Outpatient Clinic	Fallon	Nevada
United States	Foothills Urology, P.C.	Golden	Colorado
United States	Alliance Urology Specialists, PA	Greensboro	North Carolina
United States	Memorial Sloan Kettering Cancer Center Westchester	Harrison	New York
United States	Henrico Doctor's Hospital	Henrico	Virginia
United States	Houston Metro Urology	Houston	Texas
United States	First Urology, PSC	Jeffersonville	Indiana
United States	The University of Kansas Hospital	Kansas City	Kansas
United States	Lakeland Regional Health Hollis Cancer Center	Lakeland	Florida
United States	Keystone Urology Specialists	Lancaster	Pennsylvania
United States	Lancaster Urology	Lancaster	Pennsylvania
United States	Cedars-Senai OCC Pharmacy	Los Angeles	California
United States	Cedars-Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute	Los Angeles	California
United States	Comprehensive Urology - Macomb Office	Macomb	Michigan
United States	Clinical Research Solutions	Middleburg Heights	Ohio
United States	Southwest Urology	Middleburg Heights	Ohio
United States	Carolina Urologic Research Center	Myrtle Beach	South Carolina
United States	Vanderbilt Unversity Medical Center, Dept. of Urologic Surgery	Nashville	Tennessee
United States	Vanderbilt Unversity Medical Center, The Urology Clinic	Nashville	Tennessee
United States	Memorial Hospital	New York	New York
United States	Sidney Kimmel Center for Prostate and Urologic Cancers	New York	New York
United States	Eastern Connecticut Hematology Oncology Associates	Norwich	Connecticut
United States	OU Medical Center Presbyterian Tower	Oklahoma City	Oklahoma
United States	Stephenson Cancer Center	Oklahoma City	Oklahoma
United States	Stephenson Cancer Center	Oklahoma City	Oklahoma
United States	GU Research Network, LLC / Urology Cancer Center	Omaha	Nebraska
United States	University of California, Irvine Medical Center	Orange	California
United States	Kansas City Urology Care, PA	Overland Park	Kansas
United States	Jefferson Medical Oncology	Philadelphia	Pennsylvania
United States	Jefferson Urology Associates	Philadelphia	Pennsylvania
United States	Thomas Jefferson University Hospital, Bodine Buiding	Philadelphia	Pennsylvania
United States	Thomas Jefferson University, Medical Oncology	Philadelphia	Pennsylvania
United States	Thomas Jefferson University, Sidney Kimmel Cancer Center	Philadelphia	Pennsylvania
United States	Thomas Jefferson University, Sidney Kimmel Cancer Center, Clinical Research Organization	Philadelphia	Pennsylvania
United States	Premier Medical Group of the Hudson Valley PC	Poughkeepsie	New York
United States	Virginia Urology	Richmond	Virginia
United States	Memorial Sloan Kettering Cancer Center Rockville Centre	Rockville Centre	New York
United States	Sutter Medical Group	Roseville	California
United States	Sutter Medical Group, Vascular & Varicose Vein Center	Roseville	California
United States	Comprehensive Urology - Royal Oak (Stephenson) office	Royal Oak	Michigan
United States	UC Davis Comprehensive Cancer Center	Sacramento	California
United States	University of California Davis Medical Center	Sacramento	California
United States	University of California, Davis, School of Medicine	Sacramento	California
United States	Urology San Antonio Research	San Antonio	Texas
United States	Oregon Urology Institute	Springfield	Oregon
United States	Associated Medical Professionals of New York, PLLC	Syracuse	New York
United States	Chesapeake Urology Research Associates	Towson	Maryland
United States	Urological Associates of Southern Arizona, PC	Tucson	Arizona
United States	Memorial Sloan Kettering Cancer Center Nassau	Uniondale	New York
United States	Urology of Virginia, PLLC.	Virginia Beach	Virginia
United States	Johns Hopkins Kimmel Cancer Center/ Sibley Infusion	Washington	District of Columbia
United States	The University of Kansas Cancer Center and Medical Pavilion	Westwood	Kansas
United States	The University of Kansas Cancer Center, Investigational Drug Services	Westwood	Kansas
United States	GU Research Network/Wichita Urology Group	Wichita	Kansas

Sponsors (3)

Lead Sponsor	Collaborator
Pfizer	Astellas Pharma Inc, Medivation LLC, a wholly owned subsidiary of Pfizer Inc.

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Brazil,  Canada,  Denmark,  Finland,  France,  Italy,  Korea, Republic of,  Netherlands,  Poland,  Slovakia,  Spain,  Sweden,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Metastasis-free Survival (MFS) Compared Between Enzalutamide Plus Leuprolide and Placebo Plus Leuprolide	MFS was defined as the duration of time in months between randomization and the earliest objective evidence of radiographic progression by central imaging or death without radiographic progression, whichever occurred first. Radiographic progression for soft tissue disease was defined by Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1). Radiographic progression for bone disease was defined as the appearance of 1 or more metastatic lesions on bone scan (a bone scan assesses 5 regions of the skeleton, including skull, thorax, spine, pelvis, and extremities). Confirmation with a second imaging modality (plain film, computed tomography [CT], or magnetic resonance imaging [MRI]) was to be required when bone lesions were found in a single region on the bone scan. Appearance of metastatic lesions in 2 or more of the 5 regions on a bone scan was not to require confirmation with a second imaging modality.	From randomization until radiographic progression or death without radiographic progression, whichever occurred first (up to Month 98 when at least 197 MFS events occurred among the 3 treatment groups)
Secondary	Metastasis-free Survival (MFS) Compared Between Enzalutamide Monotherapy and Placebo Plus Leuprolide	MFS was defined as the duration of time in months between randomization and the earliest objective evidence of radiographic progression by central imaging or death without radiographic progression, whichever occurred first. Radiographic progression for soft tissue disease was defined by RECIST 1.1. Radiographic progression for bone disease was defined as the appearance of 1 or more metastatic lesions on bone scan (a bone scan assesses 5 regions of the skeleton, including skull, thorax, spine, pelvis, and extremities). Confirmation with a second imaging modality (plain film, CT, or MRI) was to be required when bone lesions were found in a single region on the bone scan. Appearance of metastatic lesions in 2 or more of the 5 regions on a bone scan was not to require confirmation with a second imaging modality.	From randomization until radiographic progression or death without radiographic progression, whichever occurred first (up to Month 98 when at least 197 MFS events occurred among the 3 treatment groups)
Secondary	Time to Prostate-specific Antigen (PSA) Progression	Time to PSA progression was defined as the time in months from randomization to the date of the first PSA value demonstrating progression, while participants were on study treatment, which was subsequently confirmed at least 3 weeks later. PSA progression date was defined as the date that a =25% increase and an absolute increase of =2 micrograms per liter (µg/L) (2 nanograms per milliliter [ng/mL]) above the nadir (or baseline for participants with no PSA decline by Week 25) that was confirmed by a second consecutive value at least 3 weeks later. For participants who had suspended treatment at Week 37 and later reinitiated treatment, baseline was reset as the last PSA assessment prior to or on the date of reinitiation of treatment.	From randomization until first PSA progression (up to Month 98)
Secondary	Time to First Use of New Antineoplastic Therapy	Time to first use of new antineoplastic therapy was defined as the time in months from randomization to first use of new antineoplastic therapy for prostate cancer.	From randomization until first use of new antineoplastic therapy (up to Month 98)
Secondary	Overall Survival (OS)	Overall survival was defined as the time in months between randomization and death due to any cause.	From randomization until death due to any cause (up to Month 98 when at least 197 MFS events occurred among the 3 treatment groups)
Secondary	Time to Distant Metastasis	The time to distant metastasis was defined as the time in months from randomization to the earliest objective evidence of distant soft tissue metastases or metastatic bone disease by blinded independent central review (BICR).	From randomization until the earliest objective evidence of distant soft tissue metastases or metastatic bone disease (up to Month 98)
Secondary	Percentage of Participants With Undetectable Prostate-specific Antigen (PSA) at 36 Weeks on Study Drug	Undetectable PSA at 36 weeks was serum PSA levels <0.2 ng/mL at Week 36. Percentage of participants with undetectable PSA at 36 weeks on study drug was calculated as the number of participants with undetectable PSA at Week 36 divided by the number of participants with PSA values at Week 36, and multiplied by 100.	At Week 36
Secondary	Percentage of Participants Who Remained Treatment-free 2 Years After Suspension of Study Treatment at Week 37 Due to Undetectable Prostate-specific Antigen (PSA)	Undetectable PSA at 36 weeks was serum PSA levels <0.2 ng/mL at Week 36. At Week 37, study treatment was suspended for participants whose PSA values were undetectable (<0.2 ng/mL) at Week 36 as determined by the central laboratory. Study treatment may have been suspended only once (at Week 37) due to undetectable PSA and was reinitiated if subsequent central laboratory PSA values increased to =2.0 ng/mL for participants with prior prostatectomy or =5.0 ng/mL for participants without prostatectomy. Percentage of participants who remained treatment-free 2 years after suspension of study treatment at Week 37 was calculated as the number of participants who remained treatment-free 2 years after suspension of study treatment at Week 37 divided by the number of participants with treatment suspension and multiplied by 100.	From randomization until 2 years after Week 37 (up to Month 34)
Secondary	Percentage of Participants With Undetectable Prostate-specific Antigen (PSA) 2 Years After Suspension of Treatment at Week 37 Due to Undetectable PSA	Undetectable PSA at 36 weeks was serum PSA levels <0.2 ng/mL at Week 36. At Week 37, study treatment was suspended for participants whose PSA values were undetectable (<0.2 ng/mL) at Week 36 as determined by the central laboratory. Study treatment may have been suspended only once (at Week 37) due to undetectable PSA and was reinitiated if subsequent central laboratory PSA values increased to =2.0 ng/mL for participants with prior prostatectomy or =5.0 ng/mL for participants without prostatectomy. Percentage of participants with undetectable PSA 2 years after suspension of treatment at Week 37 due to undetectable PSA was calculated as the number of participants with undetectable PSA 2 years after suspension of treatment at Week 37 due to undetectable PSA divided by the number of participants with treatment suspension and multiplied by 100.	From randomization until 2 years after Week 37 (up to Month 34)
Secondary	Time to Resumption of Any Hormonal Therapy Following Suspension at Week 37 Due to Undetectable Prostate-specific Antigen (PSA)	Undetectable PSA at 36 weeks was serum PSA levels <0.2 ng/mL at Week 36. At Week 37, study treatment was suspended for participants whose PSA values were undetectable (<0.2 ng/mL) at Week 36 as determined by the central laboratory. Study treatment may have been suspended only once (at Week 37) due to undetectable PSA and was reinitiated if subsequent central laboratory PSA values increased to =2.0 ng/mL for participants with prior prostatectomy or =5.0 ng/mL for participants without prostatectomy. The time to resumption of any hormonal therapy following suspension at Week 37 due to undetectable PSA was defined as the time in months between the date of treatment suspension at Week 37 due to undetectable PSA and the date that hormonal therapy was restarted.	From treatment suspension at Week 37 until resumption of any hormonal therapy (up to Month 98)
Secondary	Time to Castration Resistance	Time to castration resistance applied only to participants receiving leuprolide treatment and was defined as the time in months from randomization to the first occurrence of radiographic disease progression by BICR, PSA progression or symptomatic skeletal event (SSE) whichever occurred first with castrate levels of testosterone (<50 ng/dL).	From randomization to the first occurrence of radiographic disease progression, PSA progression or SSE, whichever occurred first with castrate levels of testosterone (up to Month 98)
Secondary	Time to Symptomatic Progression	Time to symptomatic progression was defined as the time in months from randomization to development of a skeletal-related event, worsening of disease-related symptoms requiring initiation of a new antineoplastic therapy, or development of adverse events (AEs) and clinically significant signs and/or symptoms due to loco-regional tumor progression requiring opiate use, surgical intervention or radiation therapy, whichever occurred first.	From randomization until the first development of events defined as symptomatic progression (up to Month 98)
Secondary	Time to First Symptomatic Skeletal Event (SSE)	Time to first symptomatic skeletal event was defined as the time in months from randomization to use of radiation therapy (external beam radiation therapy or radionuclides) or surgery to bone for prostate cancer, findings of clinically apparent pathologic bone fracture or of spinal cord compression, or new use of opiate and/or systemic antineoplastic therapy due to bone pain collected in the SSE case report form (CRF), whichever occurred first.	From randomization until the first development of events defined as SSE (up to Month 98)
Secondary	Time From Randomization to Onset of Clinically Relevant Pain Progression, Defined as a 2-point or Greater Increase From Baseline in the Brief Pain Inventory-Short Form (BPI-SF) Question 3 Score	Time to clinically relevant pain progression was defined as the time from randomization to onset of pain progression, where clinically relevant pain progression was defined as a 2-point or greater increase from baseline in the BPI-SF question 3 score. BPI-SF is a self-administered questionnaire containing 9 main questions related to pain and analgesic medication use, where question 3 (paraphrased) is "On a scale of 0 [no pain] to 10 [pain as bad as you can imagine], please rate your pain at its worst in the last 24 hours" with higher score indicating worse pain.	From randomization until a 2-point or greater increase from baseline in the BPI-SF question 3 score (up to Month 98)
Secondary	Time From Randomization to First Assessment With at Least a 10-point Decline (Deterioration) From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P) Total Score	Time to first deterioration of the FACT-P total score was defined as the time from randomization to first assessment with at least a 10-point decrease from baseline in the FACT-P total score. FACT-P total score is based on subscale scores of physical, social/family, emotional, and functional well-being, as well as 12 site-specific items to assess prostate-related symptoms, ranging 0-156, with higher score representing better quality of life.	From randomization to first assessment with at least a 10-point decrease from baseline in the FACT-P total score (up to Month 98)
Secondary	Number of Participants With Treatment-emergent Adverse Events (TEAEs) (All-causality) During On-treatment Period, Modified Treatment Period, and Treatment Reinitiation Period - at PCD Cut-off Date of 31 January 2023	An AE was any untoward medical occurrence (eg, sign, symptom, illness, disease or injury) in a participant administered study drug or other protocol-imposed intervention, regardless of attribution. TEAEs were those events with onset dates occurring during the on-treatment period for the first time. On-treatment period was the time from the date of first dose of study treatment through a minimum of 30 days after last dose of study treatment, or the start day of new antineoplastic drug therapy minus 1 day. Modified TEAEs (mTEAEs) were AEs that occurred during the modified treatment period (events occurring or worsening during the treatment suspension period after 30 days of last dose prior to treatment suspension were excluded). Reinitiated TEAEs (rTEAEs) were AEs that occurred with a start date during the dosing period after suspension and reinitiation of study treatment as defined by the reinitiation treatment period.	From first dose of study drug to the last dose + 30 days, or the day before initiation of a new antineoplastic treatment (up to Month 98)
Secondary	Number of Participants With Grade 3 or Higher Treatment-emergent Adverse Events (TEAEs) (All-causality) - at PCD Cut-off Date of 31 January 2023	An AE was any untoward medical occurrence (e.g., sign, symptom, illness, disease or injury) in a participant administered study drug or other protocol-imposed intervention, regardless of attribution. TEAEs were those events with onset dates occurring during the on-treatment period for the first time. On-treatment period was defined as the time from the date of first dose of study treatment through a minimum of 30 days after last dose of study treatment, or the start day of new antineoplastic drug therapy minus 1 day. The severity of all TEAEs was evaluated by the investigator based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03: grade 1 (mild), grade 2 (moderate), grade 3 (severe), grade 4 (potentially life-threatening) and grade 5 (death related to AE).	From first dose of study drug to the last dose + 30 days, or the day before initiation of a new antineoplastic treatment (up to Month 98)
Secondary	Number of Participants With Treatment-emergent Adverse Events (TEAEs) (Treatment-related) During On-treatment Period, Modified Treatment Period, and Treatment Reinitiation Period - at PCD Cut-off Date of 31 January 2023	An AE was any untoward medical occurrence (eg, sign, symptom, illness, disease or injury) in a participant administered study drug or other protocol-imposed intervention, regardless of attribution. TEAEs were those with onset dates occurring during the on-treatment period for the first time. On-treatment period was the time from date of first dose of study treatment through at least 30 days after last dose of study treatment or start day of new antineoplastic drug therapy minus 1 day. Treatment-related TEAEs were TEAEs attributed to study drug (enzalutamide, placebo or leuprolide). mTEAEs were AEs that occurred during the modified treatment period (events occurring or worsening during the treatment suspension period after 30 days of last dose prior to treatment suspension were excluded). rTEAEs were AEs that occurred with a start date during the dosing period after suspension and reinitiation of study treatment (reinitiation treatment period).	From first dose of study drug to the last dose + 30 days, or the day before initiation of a new antineoplastic treatment (up to Month 98)
Secondary	Number of Participants With SAEs (All-causality) During On-treatment Period, Modified Treatment Period and Treatment Reinitiation Period and SAEs (Treatment-related) During On-treatment period-at PCD Cut-off 31 Jan 2023	An AE was any untoward medical occurrence in a participant administered study drug/other protocol-imposed intervention regardless of attribution. SAEs were AEs resulting in any of the following outcomes/deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent/significant disability/incapacity; congenital anomaly. On-treatment period was time from first dose date of study treatment through =30 days after last dose of study treatment or start day of new antineoplastic drug therapy -1 day. mSAEs were SAEs occurring during modified treatment period (events occurring/worsening during treatment suspension period after 30 days of last dose prior to treatment suspension were excluded). rSAEs were SAEs occurring with a start date during the dosing period after suspension and reinitiation of study treatment. Treatment-related SAEs were attributed to any study drug.	From first dose of study drug to the last dose + 30 days, or the day before initiation of a new antineoplastic treatment (up to Month 98)
Secondary	Number of Participants With Treatment-emergent Adverse Events (TEAEs) Leading to Enzalutamide or Placebo Discontinuation - at PCD Cut-off Date of 31 January 2023	An AE was any untoward medical occurrence (eg, sign, symptom, illness, disease or injury) in a participant administered study drug or other protocol-imposed intervention, regardless of attribution. TEAEs were those events with onset dates occurring during the on-treatment period for the first time. On-treatment period was the time from the date of first dose of study treatment through a minimum of 30 days after last dose of study treatment, or the start day of new antineoplastic drug therapy minus 1 day.	From first dose of study drug to the last dose + 30 days, or the day before initiation of a new antineoplastic treatment (up to Month 98)
Secondary	Number of Participants With Shifts From Grade =2 at Baseline to Grade 3 or Grade 4 Post-baseline in Hematology Laboratory Test Values - at PCD Cut-off Date of 31 January 2023	Participants who experienced hematology laboratory test abnormalities were summarized according to worst toxicity grade observed for each hematology laboratory test. Hematology laboratory abnormalities were graded according to CTCAE version 4.03 (Grade 1: mild; Grade 2: moderate; Grade 3: severe; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death). This outcome measure calculated the number of participants with hematology laboratory abnormalities that were shifted from =Grade 2 at baseline to Grade 3 and Grade 4 post-baseline for the following parameters: hemoglobin, leukocytes, lymphocytes, neutrophils, platelets.	From first dose of study drug to the last dose + 30 days, or the day before initiation of a new antineoplastic treatment (up to Month 98)
Secondary	Number of Participants With Shifts From Grade =2 at Baseline to Grade 3 or Grade 4 Post-baseline in Chemistry Laboratory Test Values - at PCD Cut-off Date of 31 January 2023	Participants who experienced chemistry laboratory test abnormalities were summarized according to worst toxicity grade observed for each chemistry laboratory test. Chemistry laboratory abnormalities were graded according to CTCAE version 4.03 (Grade 1: mild; Grade 2: moderate; Grade 3: severe; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death). This outcome measure calculated the number of participants with chemistry laboratory abnormalities that were shifted from =Grade 2 at baseline to Grade 3 and Grade 4 post-baseline for the following parameters: alanine aminotransferase, albumin, alkaline phosphatase, aspartate aminotransferase, calcium, creatine kinase, glucose, magnesium, phosphate, potassium, sodium.	From first dose of study drug to the last dose + 30 days, or the day before initiation of a new antineoplastic treatment (up to Month 98)
Secondary	Number of Participants With Potentially Clinically Significant Vital Signs - at PCD Cut-off Date of 31 January 2023	Participants with potentially clinically significant abnormalities in vital signs were summarized for the following parameters: systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR). Potentially clinically significant abnormalities were defined as (1) SBP (mmHg): >180 and increase from baseline >40; <90 and decrease from baseline >30; final visit or 2 consecutive visits change from baseline (CFB) =10, =15, =20; final visit or most extreme result =140, =180, =140 and =20 CFB, =180 and =20 CFB; (2) DBP (mmHg): >105 and increase from baseline >30; <50 and decrease from baseline >20; final visit or 2 consecutive visits CFB =5, =10, =15; final visit or most extreme result =90, =105, =90 and =15 CFB, =105 and =15 CFB; (3) HR (bpm): >120 and increase from baseline >30; <50 and decrease from baseline >20.	From first dose of study drug to the last dose + 30 days, or the day before initiation of a new antineoplastic treatment (up to Month 98)