PREVAIL: A Safety and Efficacy Study of Oral MDV3100 in Chemotherapy-Naive Patients With Progressive Metastatic Prostate Cancer

Sponsor

Pfizer (Industry)

Overall Status

Completed

CT.gov ID

NCT01212991

Collaborator

Astellas Pharma Inc (Industry), Medivation LLC, a wholly owned subsidiary of Pfizer Inc. (Industry)

1,717

Enrollment

269

Locations

Arms

101

Actual Duration (Months)

6.4

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to determine the benefit of enzalutamide versus placebo as assessed by overall survival and progression-free survival in patients with progressive metastatic prostate cancer who have failed androgen deprivation therapy but not yet received chemotherapy.

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer	Drug: Enzalutamide Drug: Placebo	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

1717 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

PREVAIL: A MULTINATIONAL PHASE 3, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED EFFICACY AND SAFETY STUDY OF ORAL MDV3100 IN CHEMOTHERAPY-NAÏVE PATIENTS WITH PROGRESSIVE METASTATIC PROSTATE CANCER WHO HAVE FAILED ANDROGEN DEPRIVATION THERAPY

Actual Study Start Date :

Sep 16, 2010

Actual Primary Completion Date :

Sep 30, 2013

Actual Study Completion Date :

Feb 14, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Enzalutamide	Drug: Enzalutamide Participants received enzalutamide 160 mg, administered as four 40-mg capsules, once per day by mouth. Study drug treatment continued until disease progression (evidence of radiographic progression, a skeletal-related event, or clinical progression) and the initiation of a cytotoxic chemotherapy or an investigational agent, unacceptable toxicity, or withdrawal.
Placebo Comparator: Placebo	Drug: Placebo Participants received placebo, administered as four capsules, once per day by mouth. Study drug treatment continued until disease progression (evidence of radiographic progression, a skeletal-related event, or clinical progression) and the initiation of a cytotoxic chemotherapy or an investigational agent, unacceptable toxicity, or withdrawal.

Arm

Intervention/Treatment

Experimental: Enzalutamide

Drug: Enzalutamide

Participants received enzalutamide 160 mg, administered as four 40-mg capsules, once per day by mouth. Study drug treatment continued until disease progression (evidence of radiographic progression, a skeletal-related event, or clinical progression) and the initiation of a cytotoxic chemotherapy or an investigational agent, unacceptable toxicity, or withdrawal.

Placebo Comparator: Placebo

Drug: Placebo

Participants received placebo, administered as four capsules, once per day by mouth. Study drug treatment continued until disease progression (evidence of radiographic progression, a skeletal-related event, or clinical progression) and the initiation of a cytotoxic chemotherapy or an investigational agent, unacceptable toxicity, or withdrawal.

Outcome Measures

Primary Outcome Measures

Overall Survival [During study period (up to 3 years)]
Overall survival was defined as the time from randomization to death due to any cause. For patients who were alive at the time of the analysis data cutoff, overall survival was censored at the last date the patient was known to be alive or analysis data cutoff date, whichever was first. This included patients who were known to have died after the data analysis cutoff date. Patients with no post-baseline survival information were censored on the date of randomization.
Radiographic Progression-free Survival (rPFS) [During study period (up to 20 months)]
Radiographic progression-free survival was defined as the time from randomization to the first objective evidence of radiographic disease progression assessed by independent central radiology review or death due to any cause within 168 days after treatment discontinuation, whichever was first. Radiographic disease progression was evaluated by CT scan or MRI and radionuclide bone scans at regularly scheduled visits. Radiographic disease progression in bone required a confirmatory scan. Radiographic disease progression in soft tissue did not require a confirmatory scan for purposes of analysis. Radiographic disease progression was evaluated by independent central radiology review using RECIST 1.1 for soft tissue disease and PCWG2 guidelines for bone disease. Patients who did not reach the endpoint were censored at their last assessment.

Secondary Outcome Measures

Time to First Skeletal-related Event [During study period (up to 3 years)]
Time to first skeletal-related event was defined as the time from randomization to the date of the first occurrence of a skeletal-related event for each patient. A skeletal-related event was defined as radiation therapy or surgery to bone for prostate cancer, pathological bone fracture, spinal cord compression, or initiation/change in antineoplastic therapy to treat bone pain from prostate cancer. Skeletal-related events were recorded at each scheduled and unscheduled study visit and during long-term follow-up if a skeletal-related event was not documented previously. Patients who did not have a skeletal-related event at the time of the analysis data cutoff were censored at the date of last assessment indicating no evidence of skeletal-related event. Patients with no postbaseline assessments were censored on the date of randomization.
Time to Initiation of Cytotoxic Chemotherapy [During study period (up to 3 years)]
The time to initiation of cytotoxic chemotherapy is defined as the time from randomization to the date of initiation of cytotoxic chemotherapy for the treatment of prostate cancer for each patient. For patients who did not start cytotoxic chemotherapy at the time of the analysis data cutoff, time to initiation of cytotoxic chemotherapy was censored at the date of last assessment where no cytotoxic chemotherapy was indicated or at the analysis data cutoff date, whichever was first. Time to initiation of cytotoxic chemotherapy for patients with no postbaseline assessments was censored on the date of randomization.
Time to Prostate-specific Antigen (PSA) Progression [During study period (up to 3 years)]
Time to PSA progression was defined as the time from randomization to date of first confirmed observation of PSA progression for each patient. For patients with PSA declines at week 13, the PSA progression date was defined as the date that a ≥ 25% increase and an absolute increase of ≥ 2 ng/mL above the nadir was documented, and confirmed 3 or more weeks later. For patients with no PSA decline at week 13, the PSA progression date was defined as the date that a ≥ 25% increase and an absolute increase of ≥ 2 ng/mL above baseline was documented, and confirmed 3 or more weeks later. For patients who did not have confirmed PSA progression at the time of the analysis data cutoff, time to PSA progression was censored at the date of the last PSA assessment showing no evidence of confirmed PSA progression or the analysis data cutoff date, whichever was first. Time to PSA progression for patients with no postbaseline assessments was censored on the date of randomization.
Percentage of Patients With Prostate Specific Antigen (PSA) Response ≥ 50% [During study period (up to 3 years)]
PSA response was defined as a ≥ 50% reduction in PSA from baseline to the lowest postbaseline PSA value and required confirmation by a consecutive assessment at least 3 weeks later. Patients were evaluable for PSA response rate if a patient had a PSA level measured at baseline and at least one postbaseline assessment.
Best Overall Soft Tissue Response [During study period (up to 3 years)]
The best overall soft tissue objective response is defined as partial response [PR] or complete response [CR] while on study treatment based on investigator assessments of target, nontarget, and new lesions using RECIST 1.1. Soft tissue was assessed by CT or MRI at regularly scheduled visits. Only patients with measurable soft tissue disease (ie, at least 1 target lesion identified per RECIST 1.1) at screening are included in this analysis. All percentages are based on number of participants with measurable soft tissue disease at screening in each treatment group.

Other Outcome Measures

Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [Baseline to discontinuation from the study or death, whichever occurred first (maximum duration of 6.5 years)]
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug and up to a maximum of 6.5 years that were absent before treatment or that worsened relative to pretreatment state. AEs included both serious and non-serious AEs.
Number of Participants With Treatment-Emergent Adverse Events (AEs) Greater Than or Equal to (>=) Grade 3, Based on National Cancer Institute Common Terminology Criteria for AEs (CTCAE), Version 4.0 [Baseline to discontinuation from the study or death, whichever occurred first (maximum duration of 6.5 years)]
An AE is any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. As per NCI CTCAE, Grade 3 events =medically significant but not immediately life-threatening, unacceptable or intolerable events, significantly interrupting usual daily activity, require systemic drug therapy/other treatment, Grade 4 events =participant to be in imminent danger of death. Grade 5 events =death. A treatment-emergent AE (TEAE) was defined as an AE that occurred from the date and time of the first dose of study drug up to a maximum duration of 6.5 years. Number of participants with AEs of any of the Grade 3 or above (Grade 4, 5) were reported.
Number of Participants With Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs) [Baseline to discontinuation from the study or death, whichever occurred first (maximum duration of 6.5 years)]
Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug and up to a maximum duration of 6.5 years that were absent before treatment or that worsened relative to pre-treatment state. Relatedness to study drug was assessed by the investigator.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

Randomized, Double Blind Treatment Period:

Inclusion Criteria:

Histologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features
Ongoing androgen deprivation therapy with a GnRH analogue or bilateral orchiectomy
Progressive disease despite androgen deprivation therapy as defined by rising PSA levels or progressive soft tissue or bony disease
No prior treatment with cytotoxic chemotherapy
Asymptomatic or mildly symptomatic from prostate cancer

Exclusion Criteria:

Severe concurrent disease, infection, or co-morbidity that, in the judgment of the Investigator, would make the patient inappropriate for enrollment
Known or suspected brain metastasis or active leptomeningeal disease
History of another malignancy within the previous 5 years other than curatively treated non-melanomatous skin cancer

Open-Label Treatment Period:

The following inclusion criteria apply to patients receiving enzalutamide or placebo during double-blind treatment.

Eligible patients must meet all inclusion criteria.

Received randomized double-blind treatment in PREVAIL;
Open-label day 1 visit is within 6 months after this amendment is approved and becomes effective at the study site;
Is willing to maintain androgen deprivation therapy with a gonadotropin-releasing hormone (GnRH) agonist/antagonist or has had a bilateral orchiectomy;

The exclusion criteria apply only to patients starting new treatment with enzalutamide after receiving placebo as randomized treatment. Each patient must not meet any of the following criteria:

Has taken commercially available enzalutamide (Xtandi);
Severe concurrent disease, infection, or co-morbidity that, in the judgment of the Investigator, would make the patient inappropriate for enrollment
Known or suspected brain metastasis or active leptomeningeal disease

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35249
2	University of Alabama at Birmingham	Birmingham	Alabama	United States	35294
3	The University of Arizona Cancer Center-North Campus	Tucson	Arizona	United States	85719
4	The University of Arizona Cancer Certer-North Campus	Tucson	Arizona	United States	85719
5	Cancer Center Oncology Medical Group	La Mesa	California	United States	91942
6	Keck Hospital of USC	Los Angeles	California	United States	90033
7	LAC&USC Medical Center	Los Angeles	California	United States	90033
8	USC/Norris Comprehensive Cancer Center / Investigational Drug Services	Los Angeles	California	United States	90033
9	USC/Norris Comprehensive Cancer Center	Los Angeles	California	United States	90033
10	Ronald Reagan UCLA Medical Center Drug Information Center Department of Pharmaceutical Services	Los Angeles	California	United States	90095
11	UCLA Clark Urology Clinic	Los Angeles	California	United States	90095
12	North County Oncology Medical Clinic, Inc	Oceanside	California	United States	92056
13	UC Davis Medical Center	Sacramento	California	United States	95817
14	University of California Davis Comprehensive Cancer Center	Sacramento	California	United States	95817
15	Medical Oncology Associates-SD	San Diego	California	United States	92123
16	Sharp Memorial Hospital Investigational Pharmacy	San Diego	California	United States	92123
17	Sharp Rees-Stealy	San Diego	California	United States	92123
18	Stanford University Medical Center	Stanford	California	United States	94305
19	Anschutz Cancer Center Pavilion Pharmacy	Aurora	Colorado	United States	80045
20	University of Colorado Hospital, Anschutz Cancer Pavilion	Aurora	Colorado	United States	80045
21	Lynn Cancer Institute Center for Hematology Oncology	Boca Raton	Florida	United States	33486
22	Northwestern Medical Faculty Foundation	Chicago	Illinois	United States	60611
23	Northwestern Memorial Hospital	Chicago	Illinois	United States	60611
24	Jewish Hospital & St. Mary's Healthcare, Inc.	Louisville	Kentucky	United States	40245
25	Brigham & Women's Hospital	Boston	Massachusetts	United States	02115
26	Beth Israel Deaoness Medical Center	Boston	Massachusetts	United States	02215
27	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02215
28	Karmanos Cancer Institute	Detroit	Michigan	United States	48201
29	Karmanos Cancer Institute Weisberg Cancer Treatment Center	Farmington Hills	Michigan	United States	48334
30	Mayo Clinic	Rochester	Minnesota	United States	55905
31	Barnes-Jewish West County Hospital	Creve Coeur	Missouri	United States	63141
32	BJH Pharmacy	Saint Louis	Missouri	United States	63108
33	Barnes-Jewish Hospital	Saint Louis	Missouri	United States	63110
34	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
35	Barnes-Jewish St. Peters Hospital	Saint Peters	Missouri	United States	63376
36	Nebraska Methodist Hospital	Omaha	Nebraska	United States	68114
37	The Mount Sinai Medical Center	New York	New York	United States	10029
38	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10065
39	Cancer Centers of North Carolina	Cary	North Carolina	United States	27518
40	Levine Cancer Institute	Charlotte	North Carolina	United States	28203
41	Levine Cancer Institute - Main	Charlotte	North Carolina	United States	28204
42	Levine Cancer Institute - Southpark	Charlotte	North Carolina	United States	28211
43	Levine Cancer Institute - University	Charlotte	North Carolina	United States	28262
44	Levine Cancer Institute - Ballantyne	Charlotte	North Carolina	United States	28277
45	Duke University Medical Center	Durham	North Carolina	United States	27710
46	Investigational Chemotherapy Services	Durham	North Carolina	United States	27710
47	Cancer Centers of North Carolina	Raleigh	North Carolina	United States	27607
48	Portland VA Medical Center Laboratory	Portland	Oregon	United States	97239
49	Abramson Cancer Center of the University of Pennsylvania at Perelman Center for Advanced Medicine	Philadelphia	Pennsylvania	United States	19104
50	UPMC Presbyterian	Pittsburgh	Pennsylvania	United States	15213
51	UPMC Hillman Cancer Center	Pittsburgh	Pennsylvania	United States	15232
52	Hematology / Oncology MUSC Hollings Cancer Center	Charleston	South Carolina	United States	29425
53	Medical University of South Carolina - Urology Services	Charleston	South Carolina	United States	29425
54	MUSC Department of Radiology	Charleston	South Carolina	United States	29425
55	MUSC Urology Ambulatory Care	Charleston	South Carolina	United States	29425
56	MUSC Hematology / Oncology Medical Specialty Associates, East Cooper Medical Arts Center 3rd Floor	Mount Pleasant	South Carolina	United States	29464
57	MUSC Urology Medical Specialty Associates, East Cooper Medical Arts Center 3rd Floor	Mount Pleasant	South Carolina	United States	29464
58	UT Southwestern Medical Center at Dallas	Dallas	Texas	United States	75390
59	Virginia Oncology Associates	Hampton	Virginia	United States	23666
60	Virginia Oncology Associates	Newport News	Virginia	United States	23606
61	Virginia Oncology Associates	Norfolk	Virginia	United States	23502
62	Virginia Oncology Associates	Virginia Beach	Virginia	United States	23456
63	Seattle Cancer Care Alliance	Seattle	Washington	United States	98109
64	University of Washington Medical Center	Seattle	Washington	United States	98195
65	University of Wisconsin Hospital and Clinics	Madison	Wisconsin	United States	53792
66	Concord Repatriation General Hospital	Concord	New South Wales	Australia	2139
67	St George Private Hospital	Kogarah	New South Wales	Australia	2217
68	Lismore Base Hospital, Lismore Cancer Care and Haematology Unit	Lismore	New South Wales	Australia	2480
69	Liverpool Hospital	Liverpool	New South Wales	Australia	2170
70	North Coast Cancer Institute	Port Macquarie	New South Wales	Australia	2444
71	Prince of Wales Hospital	Randwick	New South Wales	Australia	2031
72	Royal North Shore Hospital, Department of Medical Oncology	St Leonards	New South Wales	Australia	2065
73	Sydney Adventist Hospital	Sydney	New South Wales	Australia	2076
74	Australian Clinical Trials Pty Ltd	Wahroonga	New South Wales	Australia	2076
75	SAN Pathology	Wahroonga	New South Wales	Australia	2076
76	SAN Radiology	Wahroonga	New South Wales	Australia	2076
77	Calvary Mater Newcastle	Waratah	New South Wales	Australia	2298
78	Westmead Hospital	Westmead	New South Wales	Australia	2145
79	Heart Care Partners	Auchenflower	Queensland	Australia	4066
80	Icon Cancer Care Wesley	Auchenflower	Queensland	Australia	4066
81	River City Pharmacy	Auchenflower	Queensland	Australia	4066
82	Icon Cancer Care Chermside	Chermside	Queensland	Australia	4032
83	University of Queensland Centre for Clinical Research (UQCCR)	Herston	Queensland	Australia	4006
84	Nuclear Medicine and Imaging Department	Herston	Queensland	Australia	4029
85	Icon Cancer Care South Brisbane	South Brisbane	Queensland	Australia	4101
86	Icon Cancer Foundation	South Brisbane	Queensland	Australia	4101
87	Mater Private Cardiology	South Brisbane	Queensland	Australia	4101
88	Adelaide Cancer Centre	Kurralta Park	South Australia	Australia	5037
89	APHS Pharmacy	Kurralta Park	South Australia	Australia	5037
90	Ashford Cancer Centre Research	Kurralta park	South Australia	Australia	5037
91	Cancer Care SA Pty Ltd	Kurralta Park	South Australia	Australia	5037
92	Bendigo Health, Bendigo Hospital	Bendigo	Victoria	Australia	3550
93	Bendigo Health Medical Imaging	Bendigo	Victoria	Australia	3552
94	Eastern Health	Box Hill	Victoria	Australia	3128
95	MIA Box Hill Radiology	Box Hill	Victoria	Australia	3128
96	Oncology Eastern Clinical Research Unit (ECRU)	Box Hill	Victoria	Australia	3128
97	Pharmacy Department	Box Hill	Victoria	Australia	3128
98	Cabrini Hospital Brighton	Brighton	Victoria	Australia	3186
99	Monash Health Translation Precinct	Clayton	Victoria	Australia	3168
100	Peter MacCallum Cancer Centre	East Melbourne	Victoria	Australia	3002
101	Barwon Health, Geelong Hospital	Geelong	Victoria	Australia	3220
102	Austin Hospital	Heidelberg	Victoria	Australia	3084
103	Cabrini Hospital Malvern	Malvern,	Victoria	Australia	3144
104	Cabrini Radiology	Malvern	Victoria	Australia	3144
105	MDI Chemer	Malvern	Victoria	Australia	3144
106	Peter MacCallum Cancer Centre	Melbourne	Victoria	Australia	3000
107	Sunshine Hospital	St Albans	Victoria	Australia	3021
108	Krankenhaus der Barmherzigen Schwestern Linz	Linz		Austria	4010
109	Ordination Dr. Fink	Salzburg		Austria	5020
110	Salzburger Universitatsklinikum	Salzburg		Austria	5020
111	Medizinische Universitaet Wien	Wien		Austria	1090
112	Cliniques Universitaires Saint-Luc	Brussels		Belgium	1200
113	AZ Sint-Lucas	Ghent		Belgium	9000
114	Jessaziekenhuis	Hasselt		Belgium	3500
115	AZ Groeninge, Campus KL	Kortrijk		Belgium	8500
116	UZ Leuven - University Hospital Gasthuisberg	Leuven		Belgium	3000
117	Centre Hospitalier Universitaire de Liege-Urologie	Liege		Belgium	4000
118	Alberta Health Services - Cancer Care, Tom Baker Cancer Centre	Calgary	Alberta	Canada	T2N 4N2
119	Tom Baker Cancer Centre - Holy Cross Site	Calgary	Alberta	Canada	T2S 3C3
120	Cross Cancer Institute	Edmonton	Alberta	Canada	T6G 1Z2
121	British Columbia Cancer Agency, Sindi Ahluwalia Hawkins, Centre for the Southern Interior	Kelowna	British Columbia	Canada	V1Y 5L3
122	Vancouver Prostate Centre	Vancouver	British Columbia	Canada	V5Z 1M9
123	Vancouver Island Health Authority-Royal Jubilee Hospital Medical Imaging	Victoria	British Columbia	Canada	V8R 1J8
124	British Columbia Cancer Agency - Vancouver Island Centre	Victoria	British Columbia	Canada	V8R 6V5
125	Manitoba Prostate Centre	Winnipeg	Manitoba	Canada	R3E 0V9
126	QEII Health Sciences Centre, Nova Scotia Cancer Centre.	Halifax	Nova Scotia	Canada	B3H 1V7
127	QEII Health Sciences Centre	Halifax	Nova Scotia	Canada	B3H 2Y9
128	QEII Health Sciences Centre	Halifax	Nova Scotia	Canada	B3H 3A7
129	Juravinski Cancer Centre at Hamilton Health Sciences	Hamilton	Ontario	Canada	L8V5C2
130	London RegCancer Program, London Health Sciences Centre	London	Ontario	Canada	N6A 4L6
131	The Ottawa Hospital Cancer Centre, General Campus	Ottawa	Ontario	Canada	K1H8L6
132	The Ottawa Hospital Cancer Centre	Ottawa	Ontario	Canada	K2H 8P4
133	Sunnybrook Health Sciences Centre	Toronto	Ontario	Canada	M4N 3M5
134	Princess Margaret Cancer Centre	Toronto	Ontario	Canada	M5G 2M9
135	Centre Hospitalier de l'Universite de Montreal	Montreal	Quebec	Canada	H2L 4M1
136	CHU de Quebec - L'Hotel-Dieu de Quebec	Quebec		Canada	G1R 2J6
137	Centre de recherche clinique el evaluative en oncologie (CRCEO)	Quebec		Canada	G1R 3S1
138	Aalborg Hospital Nord	Aalborg		Denmark	9100
139	Aarhus Universitetshospital	Aarhus N		Denmark	8200
140	Rigshospitalet	Copenhagen		Denmark	2200
141	Frederiksberg Hospital	Frederiksberg		Denmark	2000
142	Herlev Hospital	Herlev		Denmark	2730
143	Roskilde Sygehus	Roskilde		Denmark	4000
144	Docrates Clinic	Helsinki		Finland	00180
145	Helsinki University Central Hospital	Helsinki		Finland	00290
146	Oulu University Hospital	Oulu		Finland	90220
147	Tampere University Hospital	Tampere		Finland	33520
148	Hopital Civil	Strasbourg	Alsace	France	FR-67901
149	Centre Eugene Marquis-Service d'Oncologie Medicale	Rennes cedex	Bretagne	France	35042
150	Institut Bergonie	Bordeaux	Nouvelle Aquitaine	France	FR-33076
151	ICO Paul Papin	Angers		France	49055
152	Clinique Rhone Durance	Avignon		France	84000
153	Institut Bergonie	Bordeaux		France	FR-33076
154	CHD Vendee	La Roche sur Yon Cedex		France	85925
155	Centre Jean Bernard - Clinique Victor Hugo	Le Mans		France	72000
156	Centre Leon Berard	Lyon		France	69008 Cedex 08
157	Hopital Europeen Georges Pompidou	Paris Cedex 15		France	75908
158	Institut Curie	Paris		France	75005
159	Groupe Hospitalier La Pitie Salpetriere	Paris		France	75013
160	Centre de Recherche Clinique	Saint Herblain Cedex		France	44805
161	HIA Begin, Service de Medecine Interne et Oncologie	Saint-Mande		France	FR-94160
162	Institut de Cancerologie Lucien Neuwirth	Saint-Priest en Jarez		France	42271
163	Clinique Pasteur	Toulouse		France	31300
164	Institut Gustave Roussy	Villejuif		France	94805
165	Medizinische Hochschule Hannover	Hannover	Niedersachsen	Germany	30625
166	Charite-Universitaetsmedizin Berlin, Campus Benjamin Franklin	Berlin		Germany	12200
167	Staedtisches Klinikum Braunschweig gGmbH	Braunschweig		Germany	38126
168	Universitaetsklinikum Carl Gustav Carus Dresden an der	Dresden		Germany	01307
169	Martini-Klinik am UKE Gmbh	Hamburg		Germany	20246
170	Urologikum Hamburg	Hamburg		Germany	22399
171	Universitaetsklinikum Heidelberg, Klinik Fuer Urologie	Heidelberg		Germany	69120
172	Universitaetsklinikum des Saarlandes	Homburg/Saar		Germany	66424
173	Universitaetsklinikum Mannheim, Klinik fuer Urologie	Mannheim		Germany	68167
174	Universitaetsklinikum Muenster	Muenster		Germany	48149
175	Universitaetsklinikum Tuebingen, Universitaetsklinik fuer Urologie	Tuebingen		Germany	72076
176	Universitaetsklinikum Ulm	Ulm		Germany	89075
177	Kliniken Nordoberpfalz AG, Klinikum Weiden	Weiden In Der Oberpfalz		Germany	92637
178	Soroka University Medical Center	Beer Sheva		Israel	84101
179	Assaf Harofe Medical Center	Beer Yaakov		Israel	70300
180	Bnai Zion Medical Center	Haifa		Israel	31048
181	Rabin Medical Center	Petach Tikva		Israel	49100
182	The Chaim Sheba Medical Center	Ramat Gan		Israel	52621
183	Azienda Socio Sanitaria Territoriale di Cremona	Cremona	CR	Italy	26100
184	Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.)	Meldola	FC	Italy	47014
185	Azienda Ospedaliero-Universitaria San Luigi Gonzaga	Orbassano	TO	Italy	10043
186	Azienda USL8-Presidio Ospedaliero S.Donato	Arezzo		Italy	52100
187	Ospedale G.B. Morgagni	Forli		Italy	47100
188	Azienda Ospedaliera San. Camillo Forlanini	Rome		Italy	00152
189	Kyushu University Hospital	Fukuoka-shi	Fukuoka	Japan	8128582
190	Yokohama City University Hospital	Yokohama-shi	Kanagawa-ken	Japan	2360004
191	Tohoku University Hospital	Sendai-Shi	Miyagi	Japan	9800872
192	Nagasaki University Hospital	Nagasaki-shi	Nagasaki	Japan	8528501
193	Kindai University Hospital	Osaka-sayama	Osaka	Japan	5898511
194	Osaka International Cancer Institute	Osaka-shi	Osaka	Japan	5418567
195	Osaka University Hospital	Suita-shi	Osaka	Japan	5650871
196	Tokushima University Hospital	Tokushima-shi	Tokushima	Japan	7708503
197	Nippon Medical School Hospital	Bunkyo-ku	Tokyo	Japan	1138603
198	Nihon University Itabashi Hospital	Itabashi-ku	Tokyo	Japan	1738610
199	Cancer Institute Hospital	Koutou-ku	Tokyo	Japan	1358550
200	Kyorin University Hospital	Mitaka-shi	Tokyo	Japan	181 8611
201	Showa University Hospital	Shinagawa-ku	Tokyo	Japan	1428666
202	Keio University Hospital	Shinjyuku-ku	Tokyo	Japan	1608582
203	Yamaguchi University Hospital	Ube-shi	Yamaguchi	Japan	7558505
204	Chiba Cancer Center	Chiba		Japan	2608717
205	Kyoto University Hospital	Kyoto		Japan	6068507
206	Niigata University Medical and Dental Hospital	Niigata		Japan	9518520
207	Osaka City University Hospital	Osaka		Japan	5450051
208	Jikei University Hospital	Tokyo		Japan	1058471
209	Yamagata Prefectural Central Hospital	Yamagata		Japan	9902292
210	National Cancer Center	Goyang	Gyeonggi-do	Korea, Republic of	10408
211	Seoul National University Bundang Hospital	Seongnam-si	Gyeonggi-do	Korea, Republic of	13620
212	Chonnam National University Hwasun Hospital	Hwasun-eup, Hwasun-gun	Jeonnam	Korea, Republic of	619763
213	Samsung Medical Center	Gangnam-gu	Seoul	Korea, Republic of	06351
214	Asan Medical Center	Songpa-gu	Seoul	Korea, Republic of	05505
215	Severance Hospital, Yonsei University Health System	Seoul		Korea, Republic of	03722
216	Gangnam Severance Hospital, Yonsei University Health System	Seoul		Korea, Republic of	06273
217	Klaipeda University Hospital	Klaipeda		Lithuania	92288
218	Division of Oncourology, National Cancer Institute	Vilnius		Lithuania	08660
219	Vrije Universiteit Medical Center, Department of Medical Oncology	Amsterdam		Netherlands	1081 HV
220	Catharina Ziekenhuis	Eindhoven		Netherlands	5623 EJ
221	University Medical Center Groningen, Department of Urology	Groningen		Netherlands	9713 GZ
222	UMC St. Radboud	Nijmegen		Netherlands	6525 GA
223	EMC Instytut Medyczny S.A.	Wroclaw	Dolnoslaskie	Poland	54-144
224	Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Tramatologii im. M.Kopernika w Lodzi	Lodz	Lodzkie	Poland	93-509
225	Apteka Szpitalna	Gdansk	Pomorskie	Poland	80-214
226	Uniwersyteckie Centrum Kliniczne	Gdansk	Pomorskie	Poland	80-952
227	Niepubliczny Zaklad Opieki Zdrowotnej	Myslowice	Slaskie	Poland	41-400
228	Wielkopolskie Centrum Onkologii	Poznan	Wielkopolskie	Poland	61-866
229	Russian Academy of Medical Sciences Institution	Moscow		Russian Federation	115478
230	State Educational Institution of Higher Professional Education	St-Petersburg		Russian Federation	197022
231	State healthcare institute	St-Petersburg		Russian Federation	197758
232	North-Western State Medical University named after I.I.Mechnikov of the Ministry of Healthcare	St.-Petersburg		Russian Federation	191015
233	Department of Urology, National University Hospital	Singapore		Singapore	119074
234	Singapore General Hospital	Singapore		Singapore	169608
235	Fakultna nemocnica s poliklinikou F.D. Roosevelta B. bystrica	Banska Bystrica		Slovakia	975 17
236	CUIMED s.r.o.	Bratislava		Slovakia	851 05
237	Univerzitna Nemocnica Martin	Martin		Slovakia	036 59
238	UROEXAM, spol. s r.o. urologicka ambulancia	Nitra		Slovakia	949 01
239	Poliklinika Sekcov, wesper, s.r.o.	Presov		Slovakia	080 01
240	UROCENTRUM MILAB s.r.o.	Presov		Slovakia	080 01
241	Hospital Universitario German Trias i Pujol	Badalona	Barcelona	Spain	08916
242	Althaia Xarxa Asistencial Manresa	Manresa	Barcelona	Spain	08243
243	Hospital Son Espases	Palma de Mallorca	Islas Baleares	Spain	07010
244	Clínica Universidad de Navarra	Pamplona	Navarra	Spain	31008
245	Complejo Hospitalario Universitario A Coruna	A Coruna		Spain	15006
246	Hospital del Mar	Barcelona		Spain	08003
247	Hospital Vall d'Hebron	Barcelona		Spain	08035
248	Hospital Clinic i Provincial	Barcelona		Spain	08036
249	Hospital Universitario Ramon y Cajal	Madrid		Spain	28034
250	Hospital Madrid Norte Sanchinarro	Madrid		Spain	28050
251	Corporacio Sanitaria Parc Tauli	Sabadell(Barcelona)		Spain	08208
252	Sahlgrenska University Hospital	Gothenburg		Sweden	SE-413 45
253	Skane University Hospital	Malmo		Sweden	SE-205 02
254	Orebro University Hospital	Orebro		Sweden	se-701 85
255	Karolinska University Hospital Solna	Stockholm		Sweden	SE-171 76
256	Umea University Hospital	Umea		Sweden	SE-901 85
257	Bishops Wood Hospital	Northwood	Middlesex	United Kingdom	HA6 2JW
258	Mount Vernon Hospital	Northwood	Middlesex	United Kingdom	HA6 2RN
259	Oxford University Hospitals NHS Trust	Oxford	Oxfordshire	United Kingdom	OX3 7LJ
260	Royal Marsden Hospital	Sutton	Surrey	United Kingdom	SM2 5PT
261	Northern Centre for Cancer Care	Newcastle Upon Tyne	Tyne and Wear	United Kingdom	NE7 7DN
262	Velindre Cancer Centre	Cardiff	Wales	United Kingdom	CF14 2TL
263	Clatterbridge Cancer Centre NHS Foundation Trust	Bebington	Wirral, Merseyside	United Kingdom	CH63 4JY
264	Clinical Investigations and Research Unit, Royal Sussex County Hospital	Brighton, East Sussex		United Kingdom	BN2 5BE
265	University Hospitals Bristol NHS Foundation Trust	Bristol		United Kingdom	BS2 8ED
266	Edinburgh Cancer Centre	Edinburgh		United Kingdom	EH4 2XU
267	University College London Hospital NHS Trust	London		United Kingdom	NW1 2PG
268	Guy's and St Thomas' NHS Foundation Trust	London		United Kingdom	SE1 9RT
269	Imperial College Healthcare NHS Trust	London		United Kingdom	W12 0HS

Sponsors and Collaborators

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

Investigators

Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Pfizer

ClinicalTrials.gov Identifier:

NCT01212991

Other Study ID Numbers:

MDV3100-03
2010-020821-41
C3431003

First Posted:

Oct 1, 2010

Last Update Posted:

Mar 17, 2020

Last Verified:

Mar 1, 2020

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Keywords provided by Pfizer

Progressive Metastatic Prostate Cancer

Additional relevant MeSH terms:

Prostatic Neoplasms

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail	Following the independent data monitoring committee's recommendation, a protocol amendment was implemented for double-blind phase to be proceeded to open-label phase, which allowed previously placebo treated participants who had not received commercial enzalutamide the opportunity, to receive open-label access to enzalutamide.

Arm/Group Title	Enzalutamide	Placebo	Placebo Participants Crossover to Enzalutamide
Arm/Group Description	Participants received enzalutamide 160 mg, administered as four 40-mg capsules, once per day by mouth.	Participants received placebo, administered as four capsules, once per day by mouth.	Participants who received placebo in double-blind period and who agreed to proceed to open-label phase period, received enzalutamide 160 mg, administered as four 40-mg capsules, once per day by mouth.
Period Title: Double-blind
STARTED	872	845	0
Safety Population	871	844	0
COMPLETED	0	234	0
NOT COMPLETED	872	611	0
Period Title: Double-blind
STARTED	0	0	234
COMPLETED	0	0	0
NOT COMPLETED	0	0	234

Baseline Characteristics

Arm/Group Title	Enzalutamide	Placebo	Total
Arm/Group Description	Participants received enzalutamide 160 mg, administered as four 40-mg capsules, once per day by mouth.	Participants received placebo, administered as four capsules, once per day by mouth.	Total of all reporting groups
Overall Participants	872	845	1717
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	179 20.5%	179 21.2%	358 20.9%
>=65 years	693 79.5%	666 78.8%	1359 79.1%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	71.3 (8.51)	71.2 (8.42)	71.3 (8.47)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	872 100%	845 100%	1717 100%
Region of Enrollment (count of participants) [Number]
United States	127 14.6%	120 14.2%	247 14.4%
Slovakia	13 1.5%	14 1.7%	27 1.6%
Finland	18 2.1%	15 1.8%	33 1.9%
Spain	44 5%	37 4.4%	81 4.7%
Lithuania	8 0.9%	6 0.7%	14 0.8%
Austria	9 1%	9 1.1%	18 1%
Russian Federation	12 1.4%	10 1.2%	22 1.3%
Israel	14 1.6%	11 1.3%	25 1.5%
United Kingdom	78 8.9%	75 8.9%	153 8.9%
Italy	15 1.7%	15 1.8%	30 1.7%
France	85 9.7%	90 10.7%	175 10.2%
Canada	91 10.4%	88 10.4%	179 10.4%
Poland	21 2.4%	18 2.1%	39 2.3%
Belgium	28 3.2%	29 3.4%	57 3.3%
Singapore	5 0.6%	4 0.5%	9 0.5%
Australia	116 13.3%	116 13.7%	232 13.5%
Denmark	43 4.9%	44 5.2%	87 5.1%
Netherlands	15 1.7%	13 1.5%	28 1.6%
Germany	41 4.7%	42 5%	83 4.8%
Japan	28 3.2%	33 3.9%	61 3.6%
Sweden	21 2.4%	18 2.1%	39 2.3%
Korea, Republic of	40 4.6%	38 4.5%	78 4.5%

Outcome Measures

1. Primary Outcome

Title	Overall Survival
Description	Overall survival was defined as the time from randomization to death due to any cause. For patients who were alive at the time of the analysis data cutoff, overall survival was censored at the last date the patient was known to be alive or analysis data cutoff date, whichever was first. This included patients who were known to have died after the data analysis cutoff date. Patients with no post-baseline survival information were censored on the date of randomization.
Time Frame	During study period (up to 3 years)

Outcome Measure Data

Analysis Population Description
Intent to Treat (ITT) - All patients randomly assigned to treatment.

Arm/Group Title	Enzalutamide	Placebo
Arm/Group Description	Participants received enzalutamide 160 mg, administered as four 40-mg capsules, once per day by mouth.	Participants received placebo, administered as four capsules, once per day by mouth.
Measure Participants	872	845
Median (95% Confidence Interval) [months]	32.4	30.2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Enzalutamide, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	A 2-stage group sequential method (Lan DeMets OBF) assigned the level of significance for the pre-specified interim overall survival analysis (p<0.015) based on overall 2-sided type I error rate of 0.049. Final results based upon interim analysis.
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.706
	Confidence Interval	(2-Sided) 95% 0.596 to 0.837
	Parameter Dispersion	Type: Value:
	Estimation Comments	The hazard ratio is based on an unstratified Cox regression model (with treatment as the only covariate) and is relative to placebo with <1 favoring enzalutamide.

2. Primary Outcome

Title	Radiographic Progression-free Survival (rPFS)
Description	Radiographic progression-free survival was defined as the time from randomization to the first objective evidence of radiographic disease progression assessed by independent central radiology review or death due to any cause within 168 days after treatment discontinuation, whichever was first. Radiographic disease progression was evaluated by CT scan or MRI and radionuclide bone scans at regularly scheduled visits. Radiographic disease progression in bone required a confirmatory scan. Radiographic disease progression in soft tissue did not require a confirmatory scan for purposes of analysis. Radiographic disease progression was evaluated by independent central radiology review using RECIST 1.1 for soft tissue disease and PCWG2 guidelines for bone disease. Patients who did not reach the endpoint were censored at their last assessment.
Time Frame	During study period (up to 20 months)

Outcome Measure Data

Analysis Population Description
Intent to Treat (ITT) - All patients randomly assigned to treatment excluding 84 patients who were not randomized before the radiographic Progression-free Survival data cutoff date of 06 May 2012.

Arm/Group Title	Enzalutamide	Placebo
Arm/Group Description	Participants received enzalutamide 160 mg, administered as four 40-mg capsules, once per day by mouth.	Participants received placebo, administered as four capsules, once per day by mouth.
Measure Participants	832	801
Median (95% Confidence Interval) [months]	NA	3.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Enzalutamide, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	The assigned 2-sided type I error rate was 0.001 for the analysis of radiographic progression-free survival.
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.186
	Confidence Interval	(2-Sided) 95% 0.149 to 0.231
	Parameter Dispersion	Type: Value:
	Estimation Comments	The hazard ratio is based on an unstratified Cox regression model (with treatment as the only covariate) and is relative to placebo with < 1 favoring enzalutamide.

3. Secondary Outcome

Title	Time to First Skeletal-related Event
Description	Time to first skeletal-related event was defined as the time from randomization to the date of the first occurrence of a skeletal-related event for each patient. A skeletal-related event was defined as radiation therapy or surgery to bone for prostate cancer, pathological bone fracture, spinal cord compression, or initiation/change in antineoplastic therapy to treat bone pain from prostate cancer. Skeletal-related events were recorded at each scheduled and unscheduled study visit and during long-term follow-up if a skeletal-related event was not documented previously. Patients who did not have a skeletal-related event at the time of the analysis data cutoff were censored at the date of last assessment indicating no evidence of skeletal-related event. Patients with no postbaseline assessments were censored on the date of randomization.
Time Frame	During study period (up to 3 years)

Outcome Measure Data

Analysis Population Description
Intent to Treat (ITT) - All patients randomly assigned to treatment.

Arm/Group Title	Enzalutamide	Placebo
Arm/Group Description	Participants received enzalutamide 160 mg, administered as four 40-mg capsules, once per day by mouth.	Participants received placebo, administered as four capsules, once per day by mouth.
Measure Participants	872	845
Median (95% Confidence Interval) [months]	31.1	31.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Enzalutamide, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	The Holm step down method of multiple comparisons was used to maintain a study wide type I error of 5% for prespecified secondary efficacy analyses. The 2-sided type I error rate was 0.01 for this analysis.
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.718
	Confidence Interval	() 95% 0.610 to 0.844
	Parameter Dispersion	Type: Value:
	Estimation Comments	The hazard ratio is based on an unstratified Cox regression model (with treatment as the only covariate) and is relative to placebo with < 1 favoring enzalutamide.

4. Secondary Outcome

Title	Time to Initiation of Cytotoxic Chemotherapy
Description	The time to initiation of cytotoxic chemotherapy is defined as the time from randomization to the date of initiation of cytotoxic chemotherapy for the treatment of prostate cancer for each patient. For patients who did not start cytotoxic chemotherapy at the time of the analysis data cutoff, time to initiation of cytotoxic chemotherapy was censored at the date of last assessment where no cytotoxic chemotherapy was indicated or at the analysis data cutoff date, whichever was first. Time to initiation of cytotoxic chemotherapy for patients with no postbaseline assessments was censored on the date of randomization.
Time Frame	During study period (up to 3 years)

Outcome Measure Data

Analysis Population Description
Intent to Treat (ITT) - All patients randomly assigned to treatment.

Arm/Group Title	Enzalutamide	Placebo
Arm/Group Description	Participants received enzalutamide 160 mg, administered as four 40-mg capsules, once per day by mouth.	Participants received placebo, administered as four capsules, once per day by mouth.
Measure Participants	872	845
Median (95% Confidence Interval) [months]	28.0	10.8

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Enzalutamide, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	The Holm step down method of multiple comparisons was used to maintain a study wide type I error of 5% for prespecified secondary efficacy analyses. The 2-sided type I error rate was 0.0125 for this analysis.
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.349
	Confidence Interval	() 95% 0.303 to 0.403
	Parameter Dispersion	Type: Value:
	Estimation Comments	The hazard ratio is based on an unstratified Cox regression model (with treatment as the only covariate) and is relative to placebo with < 1 favoring enzalutamide.

5. Secondary Outcome

Title	Time to Prostate-specific Antigen (PSA) Progression
Description	Time to PSA progression was defined as the time from randomization to date of first confirmed observation of PSA progression for each patient. For patients with PSA declines at week 13, the PSA progression date was defined as the date that a ≥ 25% increase and an absolute increase of ≥ 2 ng/mL above the nadir was documented, and confirmed 3 or more weeks later. For patients with no PSA decline at week 13, the PSA progression date was defined as the date that a ≥ 25% increase and an absolute increase of ≥ 2 ng/mL above baseline was documented, and confirmed 3 or more weeks later. For patients who did not have confirmed PSA progression at the time of the analysis data cutoff, time to PSA progression was censored at the date of the last PSA assessment showing no evidence of confirmed PSA progression or the analysis data cutoff date, whichever was first. Time to PSA progression for patients with no postbaseline assessments was censored on the date of randomization.
Time Frame	During study period (up to 3 years)

Outcome Measure Data

Analysis Population Description
Intent to Treat (ITT) - All patients randomized.

Arm/Group Title	Enzalutamide	Placebo
Arm/Group Description	Participants received enzalutamide 160 mg, administered as four 40-mg capsules, once per day by mouth.	Participants received placebo, administered as four capsules, once per day by mouth.
Measure Participants	872	845
Median (95% Confidence Interval) [months]	11.2	2.8

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Enzalutamide, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	The Holm step down method of multiple comparisons was used to maintain a study wide type I error of 5% for prespecified secondary efficacy analyses. The 2-sided type I error rate was 0.0167 for this analysis.
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.169
	Confidence Interval	() 95% 0.147 to 0.195
	Parameter Dispersion	Type: Value:
	Estimation Comments	The hazard ratio is based on an unstratified Cox regression model (with treatment as the only covariate) and is relative to placebo with < 1 favoring enzalutamide.

6. Secondary Outcome

Title	Percentage of Patients With Prostate Specific Antigen (PSA) Response ≥ 50%
Description	PSA response was defined as a ≥ 50% reduction in PSA from baseline to the lowest postbaseline PSA value and required confirmation by a consecutive assessment at least 3 weeks later. Patients were evaluable for PSA response rate if a patient had a PSA level measured at baseline and at least one postbaseline assessment.
Time Frame	During study period (up to 3 years)

Outcome Measure Data

Analysis Population Description
Evaluable intent to treat (ITT) population - All patients randomly assigned to treatment with PSA values at baseline and at least one postbaseline assessment.

Arm/Group Title	Enzalutamide	Placebo
Arm/Group Description	Participants received enzalutamide 160 mg, administered as four 40-mg capsules, once per day by mouth.	Participants received placebo, administered as four capsules, once per day by mouth.
Measure Participants	854	777
Number (95% Confidence Interval) [Percentage of Participants]	78 8.9%	3.5 0.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Enzalutamide, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	The Holm step down method of multiple comparisons was used to maintain a study wide type I error of 5% for prespecified secondary efficacy analyses. The 2-sided type I error rate was 0.025 for this analysis.
	Method	Cochran-Mantel-Haenszel
	Comments

Method of Estimation	Estimation Parameter	Difference in response rates
	Estimated Value	74.51
	Confidence Interval	() 95% 71.45 to 77.57
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Best Overall Soft Tissue Response
Description	The best overall soft tissue objective response is defined as partial response [PR] or complete response [CR] while on study treatment based on investigator assessments of target, nontarget, and new lesions using RECIST 1.1. Soft tissue was assessed by CT or MRI at regularly scheduled visits. Only patients with measurable soft tissue disease (ie, at least 1 target lesion identified per RECIST 1.1) at screening are included in this analysis. All percentages are based on number of participants with measurable soft tissue disease at screening in each treatment group.
Time Frame	During study period (up to 3 years)

Outcome Measure Data

Analysis Population Description
Intent to treat (ITT) population With Measurable Disease - All participants who were randomly assigned to treatment and had at least one target lesion at screening.

Arm/Group Title	Enzalutamide	Placebo
Arm/Group Description	Participants received enzalutamide 160 mg, administered as four 40-mg capsules, once per day by mouth.	Participants received placebo, administered as four capsules, once per day by mouth.
Measure Participants	396	381
Number [Percentage of participants]	58.8 6.7%	5.0 0.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Enzalutamide, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	The Holm step down method of multiple comparisons was used to maintain a study wide type I error of 5% for prespecified secondary efficacy analyses. The 2-sided type I error rate was 0.05 for this analysis.
	Method	Cochran-Mantel-Haenszel
	Comments

Method of Estimation	Estimation Parameter	Difference in objective response rate
	Estimated Value	53.85
	Confidence Interval	() 95% 48.53 to 59.17
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Other Pre-specified Outcome

Title	Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug and up to a maximum of 6.5 years that were absent before treatment or that worsened relative to pretreatment state. AEs included both serious and non-serious AEs.
Time Frame	Baseline to discontinuation from the study or death, whichever occurred first (maximum duration of 6.5 years)

Outcome Measure Data

Analysis Population Description
The safety analysis set included all randomized participants who received at least 1 dose or partial dose of study drug.

Arm/Group Title	Enzalutamide	Placebo	Placebo Participants Crossover to Enzalutamide
Arm/Group Description	Participants received enzalutamide 160 mg, administered as four 40-mg capsules, once per day by mouth.	Participants received placebo, administered as four capsules, once per day by mouth.	Participants who received placebo in double-blind period and who agreed to proceed to open-label phase period, received enzalutamide 160 mg, administered as four 40-mg capsules, once per day by mouth.
Measure Participants	871	844	234
AEs	857 98.3%	791 93.6%	212 12.3%
SAEs	384 44%	229 27.1%	104 6.1%

9. Other Pre-specified Outcome

Title	Number of Participants With Treatment-Emergent Adverse Events (AEs) Greater Than or Equal to (>=) Grade 3, Based on National Cancer Institute Common Terminology Criteria for AEs (CTCAE), Version 4.0
Description	An AE is any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. As per NCI CTCAE, Grade 3 events =medically significant but not immediately life-threatening, unacceptable or intolerable events, significantly interrupting usual daily activity, require systemic drug therapy/other treatment, Grade 4 events =participant to be in imminent danger of death. Grade 5 events =death. A treatment-emergent AE (TEAE) was defined as an AE that occurred from the date and time of the first dose of study drug up to a maximum duration of 6.5 years. Number of participants with AEs of any of the Grade 3 or above (Grade 4, 5) were reported.
Time Frame	Baseline to discontinuation from the study or death, whichever occurred first (maximum duration of 6.5 years)

Outcome Measure Data

Analysis Population Description
The safety analysis set included all randomized participants who received at least 1 dose or partial dose of study drug.

Arm/Group Title	Enzalutamide	Placebo	Placebo Participants Crossover to Enzalutamide
Arm/Group Description	Participants received enzalutamide 160 mg, administered as four 40-mg capsules, once per day by mouth.	Participants received placebo, administered as four capsules, once per day by mouth.	Participants who received placebo in double-blind period and who agreed to proceed to open-label phase period, received enzalutamide 160 mg, administered as four 40-mg capsules, once per day by mouth.
Measure Participants	871	844	234
Count of Participants [Participants]	465 53.3%	318 37.6%	129 7.5%

10. Other Pre-specified Outcome

Title	Number of Participants With Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description	Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug and up to a maximum duration of 6.5 years that were absent before treatment or that worsened relative to pre-treatment state. Relatedness to study drug was assessed by the investigator.
Time Frame	Baseline to discontinuation from the study or death, whichever occurred first (maximum duration of 6.5 years)

Outcome Measure Data

Analysis Population Description
The safety analysis set included all randomized participants who received at least 1 dose or partial dose of study drug.

Arm/Group Title	Enzalutamide	Placebo	Placebo Participants Crossover to Enzalutamide
Arm/Group Description	Participants received enzalutamide 160 mg, administered as four 40-mg capsules, once per day by mouth.	Participants received placebo, administered as four capsules, once per day by mouth.	Participants who received placebo in double-blind period and who agreed to proceed to open-label phase period, received enzalutamide 160 mg, administered as four 40-mg capsules, once per day by mouth.
Measure Participants	871	844	234
AEs	579 66.4%	423 50.1%	119 6.9%
SAEs	38 4.4%	22 2.6%	14 0.8%

Adverse Events

	Enzalutamide		Placebo		Placebo Participants Crossover to Enzalutamide
Time Frame	Baseline to discontinuation from the study or death, whichever occurred first (maximum duration of 6.5 years)
Adverse Event Reporting Description	Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety set.

Arm/Group Title	Enzalutamide		Placebo		Placebo Participants Crossover to Enzalutamide
Arm/Group Description	Participants received enzalutamide 160 mg, administered as four 40-mg capsules, once per day by mouth.		Participants received placebo, administered as four capsules, once per day by mouth.		Participants who received placebo in double-blind period and who agreed to proceed to open-label phase period, received enzalutamide 160 mg, administered as four 40-mg capsules, once per day by mouth.
All Cause Mortality
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	699/871 (80.3%)		550/844 (65.2%)		166/234 (70.9%)
Serious Adverse Events
	Enzalutamide		Placebo		Placebo Participants Crossover to Enzalutamide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	384/871 (44.1%)		229/844 (27.1%)		104/234 (44.4%)
Blood and lymphatic system disorders
Anaemia	18/871 (2.1%)		9/844 (1.1%)		6/234 (2.6%)
Disseminated intravascular coagulation	1/871 (0.1%)		1/844 (0.1%)		1/234 (0.4%)
Iron deficiency anaemia	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Neutropenia	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Pancytopenia	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Haemolytic Uraemic Syndrome	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Idiopathic Thrombocytopenic Purpura	2/871 (0.2%)		0/844 (0%)		0/234 (0%)
Lymphadenopathy	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Platelet Dysfunction	0/871 (0%)		0/844 (0%)		1/234 (0.4%)
Cardiac disorders
Atrial fibrillation	10/871 (1.1%)		6/844 (0.7%)		0/234 (0%)
Acute myocardial infarction	11/871 (1.3%)		0/844 (0%)		1/234 (0.4%)
Arteriosclerosis coronary artery	1/871 (0.1%)		1/844 (0.1%)		1/234 (0.4%)
Atrioventricular block	1/871 (0.1%)		1/844 (0.1%)		0/234 (0%)
Acute coronary syndrome	5/871 (0.6%)		0/844 (0%)		0/234 (0%)
Angina pectoris	3/871 (0.3%)		0/844 (0%)		1/234 (0.4%)
Angina unstable	0/871 (0%)		1/844 (0.1%)		1/234 (0.4%)
Cardiac failure acute	0/871 (0%)		1/844 (0.1%)		0/234 (0%)
Congestive cardiomyopathy	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Hypertensive heart disease	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Sick sinus syndrome	0/871 (0%)		1/844 (0.1%)		0/234 (0%)
Sinus tachycardia	0/871 (0%)		1/844 (0.1%)		0/234 (0%)
Ventricular tachycardia	0/871 (0%)		1/844 (0.1%)		0/234 (0%)
Ventricular extrasystoles	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Atrial Flutter	0/871 (0%)		0/844 (0%)		2/234 (0.9%)
Atrial Tachycardia	0/871 (0%)		0/844 (0%)		1/234 (0.4%)
Atrioventricular Block Complete	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Bradycardia	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Cardiac Arrest	3/871 (0.3%)		2/844 (0.2%)		0/234 (0%)
Cardiac Failure	5/871 (0.6%)		2/844 (0.2%)		3/234 (1.3%)
Cardiac Failure Congestive	2/871 (0.2%)		1/844 (0.1%)		1/234 (0.4%)
Cardiopulmonary Failure	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Cardiovascular Insufficiency	0/871 (0%)		0/844 (0%)		1/234 (0.4%)
Coronary Artery Disease	6/871 (0.7%)		0/844 (0%)		0/234 (0%)
Coronary Artery Stenosis	0/871 (0%)		0/844 (0%)		1/234 (0.4%)
Ischaemic Cardiomyopathy	0/871 (0%)		0/844 (0%)		1/234 (0.4%)
Left Ventricular Failure	2/871 (0.2%)		0/844 (0%)		0/234 (0%)
Mitral Valve Disease	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Mitral Valve Incompetence	0/871 (0%)		0/844 (0%)		1/234 (0.4%)
Myocardial Infarction	6/871 (0.7%)		1/844 (0.1%)		1/234 (0.4%)
Supraventricular Tachycardia	2/871 (0.2%)		0/844 (0%)		1/234 (0.4%)
Tricuspid Valve Incompetence	0/871 (0%)		0/844 (0%)		1/234 (0.4%)
Ventricular Fibrillation	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Wolff-Parkinson-White Syndrome	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Ear and labyrinth disorders
Vertigo	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Endocrine disorders
Adrenal insufficiency	0/871 (0%)		1/844 (0.1%)		0/234 (0%)
Goitre	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Inappropriate antidiuretic hormone secretion	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Eye disorders
Amaurosis	0/871 (0%)		1/844 (0.1%)		0/234 (0%)
Cataract	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Retinal artery occlusion	2/871 (0.2%)		0/844 (0%)		0/234 (0%)
Eyelid Ptosis	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Retinal Vein Occlusion	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Gastrointestinal disorders
Constipation	5/871 (0.6%)		5/844 (0.6%)		2/234 (0.9%)
Vomiting	2/871 (0.2%)		2/844 (0.2%)		0/234 (0%)
Diarrhoea	3/871 (0.3%)		1/844 (0.1%)		1/234 (0.4%)
Nausea	3/871 (0.3%)		0/844 (0%)		2/234 (0.9%)
Upper gastrointestinal haemorrhage	4/871 (0.5%)		0/844 (0%)		0/234 (0%)
Abdominal pain	1/871 (0.1%)		1/844 (0.1%)		0/234 (0%)
Gastrointestinal haemorrhage	1/871 (0.1%)		1/844 (0.1%)		1/234 (0.4%)
Inguinal hernia	1/871 (0.1%)		1/844 (0.1%)		0/234 (0%)
Intestinal obstruction	0/871 (0%)		2/844 (0.2%)		0/234 (0%)
Melaena	1/871 (0.1%)		1/844 (0.1%)		0/234 (0%)
Small intestinal obstruction	2/871 (0.2%)		1/844 (0.1%)		1/234 (0.4%)
Duodenal ulcer haemorrhage	2/871 (0.2%)		0/844 (0%)		0/234 (0%)
Abdominal pain lower	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Diverticulum intestinal haemorrhagic	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Dysphagia	1/871 (0.1%)		1/844 (0.1%)		0/234 (0%)
Gastric ulcer haemorrhage	2/871 (0.2%)		0/844 (0%)		0/234 (0%)
Large intestinal haemorrhage	0/871 (0%)		1/844 (0.1%)		0/234 (0%)
Large intestine polyp	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Lower gastrointestinal haemorrhage	2/871 (0.2%)		0/844 (0%)		0/234 (0%)
Pancreatitis acute	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Peritoneal haemorrhage	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Rectal stenosis	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Subileus	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Duodenal ulcer	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Gastritis	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Anal Stenosis	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Gastrointestinal Ulcer	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Ileus	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Oesophageal Spasm	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Peptic Ulcer	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Rectal Haemorrhage	0/871 (0%)		0/844 (0%)		2/234 (0.9%)
General disorders
General physical health deterioration	15/871 (1.7%)		10/844 (1.2%)		6/234 (2.6%)
Disease progression	10/871 (1.1%)		7/844 (0.8%)		11/234 (4.7%)
Death	5/871 (0.6%)		1/844 (0.1%)		0/234 (0%)
Oedema peripheral	2/871 (0.2%)		3/844 (0.4%)		0/234 (0%)
Fatigue	5/871 (0.6%)		0/844 (0%)		2/234 (0.9%)
Gait disturbance	2/871 (0.2%)		1/844 (0.1%)		0/234 (0%)
Pain	3/871 (0.3%)		0/844 (0%)		0/234 (0%)
Performance status decreased	0/871 (0%)		2/844 (0.2%)		0/234 (0%)
Pyrexia	2/871 (0.2%)		1/844 (0.1%)		3/234 (1.3%)
Asthenia	0/871 (0%)		1/844 (0.1%)		5/234 (2.1%)
Chest pain	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Device dislocation	1/871 (0.1%)		1/844 (0.1%)		1/234 (0.4%)
Drowning	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Generalized oedema	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Medical device complication	0/871 (0%)		1/844 (0.1%)		1/234 (0.4%)
Non-cardiac chest pain	2/871 (0.2%)		0/844 (0%)		0/234 (0%)
Oedema	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Sudden death	0/871 (0%)		1/844 (0.1%)		0/234 (0%)
Suprapubic pain	0/871 (0%)		1/844 (0.1%)		0/234 (0%)
Adverse drug reaction	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Device occlusion	2/871 (0.2%)		1/844 (0.1%)		0/234 (0%)
Local swelling	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Device Malfunction	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Medical Device Pain	0/871 (0%)		1/844 (0.1%)		0/234 (0%)
Multi-Organ Failure	3/871 (0.3%)		0/844 (0%)		0/234 (0%)
Hepatobiliary disorders
Bile duct obstruction	0/871 (0%)		1/844 (0.1%)		0/234 (0%)
Cholecystitis	0/871 (0%)		1/844 (0.1%)		0/234 (0%)
Cholecystitis chronic	0/871 (0%)		1/844 (0.1%)		0/234 (0%)
Hepatic failure	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Hepatic function abnormal	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Jaundice	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Jaundice cholestatic	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Bile Duct Stone	1/871 (0.1%)		0/844 (0%)		1/234 (0.4%)
Cholangitis	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Hepatic Cyst	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Immune system disorders
Anaphylactic shock	0/871 (0%)		1/844 (0.1%)		0/234 (0%)
Drug hypersensitivity	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Infections and infestations
Pneumonia	14/871 (1.6%)		7/844 (0.8%)		8/234 (3.4%)
Urinary tract infection	8/871 (0.9%)		5/844 (0.6%)		10/234 (4.3%)
Urosepsis	5/871 (0.6%)		3/844 (0.4%)		4/234 (1.7%)
Sepsis	3/871 (0.3%)		4/844 (0.5%)		1/234 (0.4%)
Gastroenteritis	4/871 (0.5%)		1/844 (0.1%)		0/234 (0%)
Device related infection	2/871 (0.2%)		1/844 (0.1%)		0/234 (0%)
Bronchitis	1/871 (0.1%)		1/844 (0.1%)		0/234 (0%)
Cellulitis	2/871 (0.2%)		1/844 (0.1%)		0/234 (0%)
Herpes zoster	1/871 (0.1%)		1/844 (0.1%)		0/234 (0%)
Appendicitis	0/871 (0%)		1/844 (0.1%)		0/234 (0%)
Appendicitis perforated	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Bacteraemia	0/871 (0%)		1/844 (0.1%)		0/234 (0%)
Diverticulitis	2/871 (0.2%)		0/844 (0%)		0/234 (0%)
Gallbladder abscess	0/871 (0%)		1/844 (0.1%)		0/234 (0%)
Gastroenteritis staphylococcal	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Lower respiratory tract infection	2/871 (0.2%)		0/844 (0%)		0/234 (0%)
Osteomyelitis	0/871 (0%)		1/844 (0.1%)		0/234 (0%)
Peritonitis	1/871 (0.1%)		0/844 (0%)		1/234 (0.4%)
Respiratory tract infection	0/871 (0%)		1/844 (0.1%)		0/234 (0%)
Septic shock	0/871 (0%)		1/844 (0.1%)		0/234 (0%)
Urinary tract infection fungal	0/871 (0%)		1/844 (0.1%)		0/234 (0%)
Viral infection	0/871 (0%)		1/844 (0.1%)		0/234 (0%)
Wound infection	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Chronic sinusitis	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Acute Sinusitis	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Arthritis Bacterial	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Cholecystitis Infective	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Clostridium Difficile Colitis	0/871 (0%)		0/844 (0%)		1/234 (0.4%)
Clostridium Difficile Sepsis	0/871 (0%)		0/844 (0%)		1/234 (0.4%)
Erysipelas	0/871 (0%)		0/844 (0%)		1/234 (0.4%)
Escherichia Urinary Tract Infection	0/871 (0%)		0/844 (0%)		1/234 (0.4%)
Infected Dermal Cyst	0/871 (0%)		0/844 (0%)		1/234 (0.4%)
Infection	2/871 (0.2%)		0/844 (0%)		3/234 (1.3%)
Meningitis Pneumococcal	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Postoperative Wound Infection	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Pulmonary Sepsis	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Pyelonephritis Acute	0/871 (0%)		0/844 (0%)		1/234 (0.4%)
Upper Respiratory Tract Infection	0/871 (0%)		0/844 (0%)		2/234 (0.9%)
Injury, poisoning and procedural complications
Fall	12/871 (1.4%)		3/844 (0.4%)		2/234 (0.9%)
Femoral neck fracture	7/871 (0.8%)		0/844 (0%)		0/234 (0%)
Femur fracture	3/871 (0.3%)		2/844 (0.2%)		1/234 (0.4%)
Spinal compression fracture	4/871 (0.5%)		1/844 (0.1%)		0/234 (0%)
Road traffic accident	2/871 (0.2%)		1/844 (0.1%)		0/234 (0%)
Humerus fracture	4/871 (0.5%)		0/844 (0%)		1/234 (0.4%)
Wrist fracture	3/871 (0.3%)		0/844 (0%)		0/234 (0%)
Hip fracture	3/871 (0.3%)		2/844 (0.2%)		1/234 (0.4%)
Subdural haematoma	0/871 (0%)		2/844 (0.2%)		2/234 (0.9%)
Toxicity to various agents	2/871 (0.2%)		0/844 (0%)		0/234 (0%)
Cystitis radiation	2/871 (0.2%)		0/844 (0%)		0/234 (0%)
Ankle fracture	1/871 (0.1%)		1/844 (0.1%)		0/234 (0%)
Chest injury	0/871 (0%)		1/844 (0.1%)		0/234 (0%)
Clavicle fracture	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Extradural haematoma	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Facial bones fracture	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Foreign body	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Gastroenteritis radiation	2/871 (0.2%)		0/844 (0%)		0/234 (0%)
Hand fracture	0/871 (0%)		1/844 (0.1%)		0/234 (0%)
Head injury	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Lumbar vertebral fracture	1/871 (0.1%)		1/844 (0.1%)		0/234 (0%)
Post procedural haemorrhage	0/871 (0%)		1/844 (0.1%)		0/234 (0%)
Radiation oesophagitis	0/871 (0%)		1/844 (0.1%)		0/234 (0%)
Radius fracture	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Skeletal injury	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Subdural haemorrhage	1/871 (0.1%)		1/844 (0.1%)		0/234 (0%)
Tibia fracture	0/871 (0%)		1/844 (0.1%)		0/234 (0%)
Traumatic fracture	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Traumatic intracranial haemorrhage	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Upper limb fracture	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Contrast media reaction	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Contusion	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Lower limb fracture	2/871 (0.2%)		0/844 (0%)		0/234 (0%)
Post procedural haematuria	0/871 (0%)		1/844 (0.1%)		0/234 (0%)
Procedural pain	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Pubis fracture	0/871 (0%)		1/844 (0.1%)		0/234 (0%)
Vascular pseudoaneurysm	2/871 (0.2%)		0/844 (0%)		0/234 (0%)
Back Injury	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Cervical Vertebral Fracture	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Joint Injury	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Post Procedural Bile Leak	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Renal Haematoma	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Rib Fracture	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Spinal Fracture	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Sternal Fracture	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Thoracic Vertebral Fracture	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Investigations
Electrocardiogram QT prolonged	1/871 (0.1%)		1/844 (0.1%)		0/234 (0%)
Haemoglobin decreased	2/871 (0.2%)		0/844 (0%)		0/234 (0%)
Platelet count decreased	1/871 (0.1%)		1/844 (0.1%)		1/234 (0.4%)
Hepatic enzyme increased	0/871 (0%)		2/844 (0.2%)		0/234 (0%)
Arteriogram coronary	0/871 (0%)		1/844 (0.1%)		0/234 (0%)
Blood creatinine increased	0/871 (0%)		1/844 (0.1%)		0/234 (0%)
Coagulation time prolonged	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Eastern cooperative oncology group performance status worsened	0/871 (0%)		1/844 (0.1%)		0/234 (0%)
International normalized ratio increased	0/871 (0%)		1/844 (0.1%)		0/234 (0%)
Electrocardiogram repolarisation abnormality	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Weight decreased	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Biopsy	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Ejection Fraction Decreased	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Electrocardiogram Abnormal	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Metabolism and nutrition disorders
Dehydration	2/871 (0.2%)		3/844 (0.4%)		1/234 (0.4%)
Decreased appetite	2/871 (0.2%)		2/844 (0.2%)		1/234 (0.4%)
Hypercalcaemia	3/871 (0.3%)		0/844 (0%)		0/234 (0%)
Hypoglycaemia	1/871 (0.1%)		1/844 (0.1%)		0/234 (0%)
Cachexia	1/871 (0.1%)		1/844 (0.1%)		0/234 (0%)
Fluid retention	0/871 (0%)		1/844 (0.1%)		0/234 (0%)
Hyperkalaemia	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Hypokalaemia	2/871 (0.2%)		0/844 (0%)		0/234 (0%)
Hyponatraemia	0/871 (0%)		1/844 (0.1%)		0/234 (0%)
Type 2 diabetes mellitus	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Metabolic acidosis	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Hypophagia	0/871 (0%)		0/844 (0%)		1/234 (0.4%)
Malnutrition	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Musculoskeletal and connective tissue disorders
Pathological Fracture	15/871 (1.7%)		6/844 (0.7%)		3/234 (1.3%)
Back pain	4/871 (0.5%)		5/844 (0.6%)		0/234 (0%)
Bone pain	3/871 (0.3%)		5/844 (0.6%)		0/234 (0%)
Osteoarthritis	8/871 (0.9%)		2/844 (0.2%)		2/234 (0.9%)
Intervertebral disc protrusion	4/871 (0.5%)		1/844 (0.1%)		0/234 (0%)
Muscular weakness	1/871 (0.1%)		2/844 (0.2%)		1/234 (0.4%)
Musculoskeletal chest pain	0/871 (0%)		3/844 (0.4%)		0/234 (0%)
Arthralgia	2/871 (0.2%)		0/844 (0%)		1/234 (0.4%)
Neck pain	0/871 (0%)		2/844 (0.2%)		0/234 (0%)
Osteolysis	0/871 (0%)		2/844 (0.2%)		0/234 (0%)
Spinal column stenosis	2/871 (0.2%)		0/844 (0%)		0/234 (0%)
Lumbar spinal stenosis	1/871 (0.1%)		1/844 (0.1%)		1/234 (0.4%)
Musculoskeletal pain	1/871 (0.1%)		0/844 (0%)		1/234 (0.4%)
Myalgia	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Myopathy	0/871 (0%)		1/844 (0.1%)		0/234 (0%)
Periostitis	0/871 (0%)		1/844 (0.1%)		0/234 (0%)
Rhabdomyolysis	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Spinal osteoarthritis	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Arthritis	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Groin pain	1/871 (0.1%)		1/844 (0.1%)		0/234 (0%)
Pain in extremity	1/871 (0.1%)		1/844 (0.1%)		0/234 (0%)
Bursitis	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Cervical Spinal Stenosis	0/871 (0%)		0/844 (0%)		1/234 (0.4%)
Synovial Cyst	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastatic pain	18/871 (2.1%)		17/844 (2%)		4/234 (1.7%)
Cancer pain	3/871 (0.3%)		3/844 (0.4%)		2/234 (0.9%)
Gastric cancer	2/871 (0.2%)		1/844 (0.1%)		0/234 (0%)
Transitional cell carcinoma	4/871 (0.5%)		0/844 (0%)		2/234 (0.9%)
Adenocarcinoma of colon	2/871 (0.2%)		1/844 (0.1%)		0/234 (0%)
Lung adenocarcinoma	1/871 (0.1%)		1/844 (0.1%)		0/234 (0%)
Malignant pleural effusion	1/871 (0.1%)		1/844 (0.1%)		0/234 (0%)
Metastases to central nervous system	2/871 (0.2%)		1/844 (0.1%)		0/234 (0%)
Metastases to liver	0/871 (0%)		2/844 (0.2%)		0/234 (0%)
Metastases to meninges	1/871 (0.1%)		1/844 (0.1%)		1/234 (0.4%)
Metastases to soft tissue	1/871 (0.1%)		1/844 (0.1%)		0/234 (0%)
Metastases to spine	2/871 (0.2%)		0/844 (0%)		0/234 (0%)
Prostate cancer metastatic	0/871 (0%)		2/844 (0.2%)		1/234 (0.4%)
Rectal cancer	2/871 (0.2%)		0/844 (0%)		0/234 (0%)
Malignant melanoma	2/871 (0.2%)		0/844 (0%)		0/234 (0%)
Prostate cancer	1/871 (0.1%)		1/844 (0.1%)		1/234 (0.4%)
Tonsil cancer	2/871 (0.2%)		0/844 (0%)		0/234 (0%)
Adenocarcinoma gastric	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Anal cancer	0/871 (0%)		1/844 (0.1%)		0/234 (0%)
Bladder cancer	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Bladder transitional cell carcinoma	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Colon cancer	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Colorectal cancer	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Hepatocellular carcinoma	3/871 (0.3%)		0/844 (0%)		0/234 (0%)
Intestinal adenocarcinoma	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Lung neoplasm malignant	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Metastases to bladder	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Metastases to bone	2/871 (0.2%)		0/844 (0%)		0/234 (0%)
Metastases to bone marrow	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Metastases to breast	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Metastases to lung	0/871 (0%)		1/844 (0.1%)		2/234 (0.9%)
Metastases to peritoneum	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Neuroendocrine carcinoma of the skin	0/871 (0%)		1/844 (0.1%)		0/234 (0%)
Osteosarcoma	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Renal cell carcinoma	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Small cell lung cancer limited stage	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Thyroid adenoma	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Tumour associated fever	0/871 (0%)		1/844 (0.1%)		1/234 (0.4%)
Tumour embolism	0/871 (0%)		1/844 (0.1%)		0/234 (0%)
Tumour pain	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
B-cell lymphoma	3/871 (0.3%)		0/844 (0%)		0/234 (0%)
Gastrointestinal stromal tumour	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Myelodysplastic syndrome	0/871 (0%)		1/844 (0.1%)		0/234 (0%)
Acute Myeloid Leukaemia	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Basal Cell Carcinoma	2/871 (0.2%)		0/844 (0%)		0/234 (0%)
Brain Neoplasm	0/871 (0%)		0/844 (0%)		1/234 (0.4%)
Colorectal Adenocarcinoma	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Colorectal Cancer Metastatic	0/871 (0%)		0/844 (0%)		1/234 (0.4%)
Diffuse Large B-Cell Lymphoma	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Gastric Cancer Recurrent	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Gastrointestinal Cancer Metastatic	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Glioblastoma Multiforme	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Metastases To Chest Wall	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Metastases To Penis	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Metastatic Neoplasm	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Myxofibrosarcoma	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Non-Hodgkin's Lymphoma	1/871 (0.1%)		0/844 (0%)		1/234 (0.4%)
Plasma Cell Myeloma	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Small Cell Lung Cancer	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Squamous Cell Carcinoma Of Skin	0/871 (0%)		0/844 (0%)		1/234 (0.4%)
Nervous system disorders
Spinal cord compression	35/871 (4%)		25/844 (3%)		10/234 (4.3%)
Syncope	8/871 (0.9%)		0/844 (0%)		3/234 (1.3%)
Cerebrovascular accident	7/871 (0.8%)		1/844 (0.1%)		0/234 (0%)
Cauda equina syndrome	4/871 (0.5%)		0/844 (0%)		0/234 (0%)
Nerve root compression	2/871 (0.2%)		2/844 (0.2%)		0/234 (0%)
Transient ischaemic attack	6/871 (0.7%)		3/844 (0.4%)		0/234 (0%)
Presyncope	3/871 (0.3%)		0/844 (0%)		0/234 (0%)
Paraesthesia	0/871 (0%)		2/844 (0.2%)		0/234 (0%)
Paraparesis	1/871 (0.1%)		1/844 (0.1%)		0/234 (0%)
Ataxia	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Brain injury	0/871 (0%)		1/844 (0.1%)		0/234 (0%)
Cerebral haemorrhage	1/871 (0.1%)		1/844 (0.1%)		0/234 (0%)
Cerebral infarction	2/871 (0.2%)		0/844 (0%)		0/234 (0%)
Cervicobrachial syndrome	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Coma hepatic	0/871 (0%)		1/844 (0.1%)		0/234 (0%)
Dementia	0/871 (0%)		1/844 (0.1%)		0/234 (0%)
Memory impairment	0/871 (0%)		1/844 (0.1%)		0/234 (0%)
Meningorrhagia	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Metabolic encephalopathy	0/871 (0%)		1/844 (0.1%)		0/234 (0%)
Reversible ischaemic neurological deficit	0/871 (0%)		1/844 (0.1%)		0/234 (0%)
Spinal cord ischaemia	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Subarachnoid haemorrhage	2/871 (0.2%)		0/844 (0%)		0/234 (0%)
Vith nerve disorder	0/871 (0%)		1/844 (0.1%)		0/234 (0%)
Complex partial seizures	0/871 (0%)		1/844 (0.1%)		0/234 (0%)
Neuralgia	1/871 (0.1%)		0/844 (0%)		1/234 (0.4%)
Sciatica	0/871 (0%)		2/844 (0.2%)		0/234 (0%)
Cervical Cord Compression	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Convulsion	1/871 (0.1%)		0/844 (0%)		1/234 (0.4%)
Cranial Nerve Paralysis	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Grand Mal Convulsion	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Haemorrhage Intracranial	2/871 (0.2%)		0/844 (0%)		0/234 (0%)
Headache	1/871 (0.1%)		0/844 (0%)		1/234 (0.4%)
Hypoxic-Ischaemic Encephalopathy	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Lethargy	0/871 (0%)		1/844 (0.1%)		0/234 (0%)
Loss Of Consciousness	1/871 (0.1%)		0/844 (0%)		1/234 (0.4%)
Neurological Symptom	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Sensory Loss	0/871 (0%)		0/844 (0%)		1/234 (0.4%)
Vith Nerve Paralysis	0/871 (0%)		0/844 (0%)		1/234 (0.4%)
Dizziness	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Epiduritis	0/871 (0%)		0/844 (0%)		1/234 (0.4%)
Monoplegia	0/871 (0%)		0/844 (0%)		1/234 (0.4%)
Status Epilepticus	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Psychiatric disorders
Confusional state	1/871 (0.1%)		4/844 (0.5%)		2/234 (0.9%)
Suicide attempt	1/871 (0.1%)		1/844 (0.1%)		1/234 (0.4%)
Depression	0/871 (0%)		1/844 (0.1%)		0/234 (0%)
Major depression	0/871 (0%)		1/844 (0.1%)		0/234 (0%)
Delirium	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Renal and urinary disorders
Urinary retention	10/871 (1.1%)		13/844 (1.5%)		3/234 (1.3%)
Haematuria	11/871 (1.3%)		12/844 (1.4%)		3/234 (1.3%)
Urinary tract obstruction	8/871 (0.9%)		9/844 (1.1%)		1/234 (0.4%)
Hydronephrosis	2/871 (0.2%)		11/844 (1.3%)		1/234 (0.4%)
Renal failure acute	6/871 (0.7%)		5/844 (0.6%)		2/234 (0.9%)
Ureteric obstruction	4/871 (0.5%)		4/844 (0.5%)		1/234 (0.4%)
Obstructive uropathy	5/871 (0.6%)		6/844 (0.7%)		3/234 (1.3%)
Bladder outlet obstruction	2/871 (0.2%)		3/844 (0.4%)		0/234 (0%)
Postrenal failure	2/871 (0.2%)		3/844 (0.4%)		0/234 (0%)
Urinary bladder haemorrhage	3/871 (0.3%)		0/844 (0%)		0/234 (0%)
Calculus bladder	1/871 (0.1%)		1/844 (0.1%)		1/234 (0.4%)
Prerenal failure	1/871 (0.1%)		1/844 (0.1%)		0/234 (0%)
Renal failure	3/871 (0.3%)		1/844 (0.1%)		0/234 (0%)
Acute prerenal failure	0/871 (0%)		1/844 (0.1%)		0/234 (0%)
Bladder obstruction	0/871 (0%)		1/844 (0.1%)		0/234 (0%)
Renal failure chronic	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Urethral meatus stenosis	0/871 (0%)		1/844 (0.1%)		0/234 (0%)
Urethral obstruction	0/871 (0%)		1/844 (0.1%)		0/234 (0%)
Urine flow decreased	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Bladder neck obstruction	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Micturition urgency	0/871 (0%)		1/844 (0.1%)		0/234 (0%)
Calculus Ureteric	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Nephrolithiasis	2/871 (0.2%)		0/844 (0%)		0/234 (0%)
Renal Colic	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Urethral Stenosis	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Urinary Incontinence	0/871 (0%)		0/844 (0%)		1/234 (0.4%)
Nephrotic Syndrome	0/871 (0%)		0/844 (0%)		1/234 (0.4%)
Calculus Urinary	2/871 (0.2%)		0/844 (0%)		0/234 (0%)
Reproductive system and breast disorders
Benign prostatic hyperplasia	0/871 (0%)		1/844 (0.1%)		0/234 (0%)
Pelvic pain	1/871 (0.1%)		0/844 (0%)		1/234 (0.4%)
Prostatic obstruction	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Prostatitis	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Testicular pain	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Epididymitis	0/871 (0%)		0/844 (0%)		1/234 (0.4%)
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	6/871 (0.7%)		7/844 (0.8%)		0/234 (0%)
Chronic obstructive pulmonary disease	5/871 (0.6%)		3/844 (0.4%)		0/234 (0%)
Dyspnoea	3/871 (0.3%)		2/844 (0.2%)		0/234 (0%)
Pleural effusion	2/871 (0.2%)		1/844 (0.1%)		0/234 (0%)
Epistaxis	1/871 (0.1%)		1/844 (0.1%)		0/234 (0%)
Acute pulmonary oedema	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Aspiration	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Asthma	0/871 (0%)		1/844 (0.1%)		0/234 (0%)
Haemothorax	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Hydrothorax	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Hypoxia	0/871 (0%)		1/844 (0.1%)		0/234 (0%)
Nasal polyps	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Organising pneumonia	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Pneumonia aspiration	3/871 (0.3%)		0/844 (0%)		1/234 (0.4%)
Pneumonitis	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Pulmonary haemorrhage	0/871 (0%)		1/844 (0.1%)		0/234 (0%)
Restrictive pulmonary disease	0/871 (0%)		1/844 (0.1%)		0/234 (0%)
Tracheal obstruction extrinsic	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Bronchiectasis	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Pneumothorax	2/871 (0.2%)		1/844 (0.1%)		1/234 (0.4%)
Skin and subcutaneous tissue disorders
Toxic skin eruption	2/871 (0.2%)		0/844 (0%)		0/234 (0%)
Rash	1/871 (0.1%)		0/844 (0%)		1/234 (0.4%)
Swelling face	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Rash Maculo-Papular	0/871 (0%)		0/844 (0%)		1/234 (0.4%)
Surgical and medical procedures
Cancer hormonal therapy	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Pain management	0/871 (0%)		1/844 (0.1%)		0/234 (0%)
Knee Arthroplasty	0/871 (0%)		0/844 (0%)		1/234 (0.4%)
Radical Cystectomy	0/871 (0%)		0/844 (0%)		1/234 (0.4%)
Umbilical Hernia Repair	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Vascular disorders
Deep vein thrombosis	4/871 (0.5%)		2/844 (0.2%)		0/234 (0%)
Hypertension	4/871 (0.5%)		0/844 (0%)		1/234 (0.4%)
Hypotension	1/871 (0.1%)		1/844 (0.1%)		0/234 (0%)
Orthostatic hypotension	1/871 (0.1%)		1/844 (0.1%)		0/234 (0%)
Aortic aneurysm	1/871 (0.1%)		1/844 (0.1%)		0/234 (0%)
Aortic aneurysm rupture	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Circulatory collapse	2/871 (0.2%)		0/844 (0%)		0/234 (0%)
Hypovolaemic shock	1/871 (0.1%)		0/844 (0%)		1/234 (0.4%)
Lymphoedema	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Vena cava thrombosis	0/871 (0%)		1/844 (0.1%)		0/234 (0%)
Aortic stenosis	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Phlebitis	0/871 (0%)		1/844 (0.1%)		0/234 (0%)
Subclavian artery stenosis	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Aneurysm	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Peripheral Artery Stenosis	1/871 (0.1%)		0/844 (0%)		0/234 (0%)
Other (Not Including Serious) Adverse Events
	Enzalutamide		Placebo		Placebo Participants Crossover to Enzalutamide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	814/871 (93.5%)		723/844 (85.7%)		180/234 (76.9%)
Blood and lymphatic system disorders
Anaemia	76/871 (8.7%)		68/844 (8.1%)		23/234 (9.8%)
Gastrointestinal disorders
Nausea	211/871 (24.2%)		192/844 (22.7%)		34/234 (14.5%)
Constipation	220/871 (25.3%)		145/844 (17.2%)		38/234 (16.2%)
Diarrhoea	160/871 (18.4%)		121/844 (14.3%)		20/234 (8.5%)
Vomiting	64/871 (7.3%)		70/844 (8.3%)		9/234 (3.8%)
Abdominal pain	56/871 (6.4%)		31/844 (3.7%)		4/234 (1.7%)
General disorders
Fatigue	332/871 (38.1%)		220/844 (26.1%)		63/234 (26.9%)
Asthenia	122/871 (14%)		69/844 (8.2%)		15/234 (6.4%)
Oedema peripheral	115/871 (13.2%)		70/844 (8.3%)		20/234 (8.5%)
Infections and infestations
Urinary tract infection	70/871 (8%)		56/844 (6.6%)		11/234 (4.7%)
Nasopharyngitis	74/871 (8.5%)		44/844 (5.2%)		6/234 (2.6%)
Upper respiratory tract infection	61/871 (7%)		30/844 (3.6%)		7/234 (3%)
Injury, poisoning and procedural complications
Fall	136/871 (15.6%)		42/844 (5%)		15/234 (6.4%)
Investigations
Weight decreased	122/871 (14%)		72/844 (8.5%)		26/234 (11.1%)
Metabolism and nutrition disorders
Decreased appetite	182/871 (20.9%)		139/844 (16.5%)		36/234 (15.4%)
Musculoskeletal and connective tissue disorders
Back pain	280/871 (32.1%)		188/844 (22.3%)		32/234 (13.7%)
Arthralgia	206/871 (23.7%)		137/844 (16.2%)		22/234 (9.4%)
Pain in extremity	124/871 (14.2%)		97/844 (11.5%)		13/234 (5.6%)
Bone pain	100/871 (11.5%)		116/844 (13.7%)		18/234 (7.7%)
Musculoskeletal pain	112/871 (12.9%)		74/844 (8.8%)		28/234 (12%)
Musculoskeletal chest pain	73/871 (8.4%)		40/844 (4.7%)		5/234 (2.1%)
Myalgia	59/871 (6.8%)		49/844 (5.8%)		8/234 (3.4%)
Muscular Weakness	45/871 (5.2%)		27/844 (3.2%)		8/234 (3.4%)
Nervous system disorders
Headache	102/871 (11.7%)		59/844 (7%)		15/234 (6.4%)
Dizziness	85/871 (9.8%)		54/844 (6.4%)		13/234 (5.6%)
Dysgeusia	67/871 (7.7%)		31/844 (3.7%)		5/234 (2.1%)
Psychiatric disorders
Insomnia	78/871 (9%)		48/844 (5.7%)		10/234 (4.3%)
Renal and urinary disorders
Haematuria	93/871 (10.7%)		43/844 (5.1%)		11/234 (4.7%)
Pollakiuria	62/871 (7.1%)		37/844 (4.4%)		6/234 (2.6%)
Respiratory, thoracic and mediastinal disorders
Cough	95/871 (10.9%)		58/844 (6.9%)		2/234 (0.9%)
Dyspnoea	88/871 (10.1%)		60/844 (7.1%)		14/234 (6%)
Skin and subcutaneous tissue disorders
Rash	31/871 (3.6%)		21/844 (2.5%)		14/234 (6%)
Vascular disorders
Hot flush	159/871 (18.3%)		66/844 (7.8%)		11/234 (4.7%)
Hypertension	148/871 (17%)		36/844 (4.3%)		28/234 (12%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

PI agrees not to independently publish the results before the publication of the multi-center PI paper. Sponsor shall review and comment 30 days prior to submission or disclosure. If publication or disclosure contains Sponsor Confidential Information, other than study data, PI agrees to remove Confidential Information from publication or disclosure. Sponsor may request that PI delay such publication for an additional 60 days to protect the patentability of any invention described.

Results Point of Contact

Name/Title	Pfizer ClinicalTrials.gov Call Center
Organization	Pfizer Inc.
Phone	8007181021
Email	ClinicalTrials.gov_Inquiries@pfizer.com

Responsible Party:

Pfizer

ClinicalTrials.gov Identifier:

NCT01212991

Other Study ID Numbers:

MDV3100-03
2010-020821-41
C3431003

First Posted:

Oct 1, 2010

Last Update Posted:

Mar 17, 2020

Last Verified:

Mar 1, 2020

PREVAIL: A Safety and Efficacy Study of Oral MDV3100 in Chemotherapy-Naive Patients With Progressive Metastatic Prostate Cancer

Study Details

Study Description

Brief Summary

Study Design

Arms and Interventions

Outcome Measures

Primary Outcome Measures

Secondary Outcome Measures

Other Outcome Measures

Eligibility Criteria

Criteria

Randomized, Double Blind Treatment Period:

Inclusion Criteria:

Exclusion Criteria:

Open-Label Treatment Period:

Contacts and Locations

Locations

Sponsors and Collaborators

Investigators

Study Documents (Full-Text)

More Information

Publications

Study Results

Participant Flow

Baseline Characteristics

Outcome Measures

Outcome Measure Data

Statistical Analysis 1

Outcome Measure Data

Statistical Analysis 1

Outcome Measure Data

Statistical Analysis 1

Outcome Measure Data

Statistical Analysis 1

Outcome Measure Data

Statistical Analysis 1

Outcome Measure Data

Statistical Analysis 1

Outcome Measure Data

Statistical Analysis 1

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Adverse Events

All Cause Mortality

Serious Adverse Events

Other (Not Including Serious) Adverse Events

Limitations/Caveats

More Information

Certain Agreements

Results Point of Contact