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Study Comparing Orteronel Plus Prednisone in Participants With Chemotherapy-Naive Metastatic Castration-Resistant Prostate Cancer

Sponsor
Millennium Pharmaceuticals, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT01193244
Collaborator
(none)
1,560
Enrollment
245
Locations
2
Arms
66.2
Actual Duration (Months)
6.4
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a randomized, double-blind, multicenter, phase 3 study evaluating orteronel (TAK-700) plus prednisone compared with placebo plus prednisone in the treatment of men with progressive, chemotherapy-naive, metastatic, castration-resistant prostate cancer (mCRPC)

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
1560 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
A Phase 3, Randomized, Double-Blind, Multicenter Trial Comparing Orteronel Plus Prednisone With Placebo Plus Prednisone in Patients With Chemotherapy-Naive Metastatic Castration-Resistant Prostate Cancer
Actual Study Start Date :
Oct 1, 2010
Actual Primary Completion Date :
Jan 1, 2014
Actual Study Completion Date :
Apr 7, 2016

Arms and Interventions

Arm Intervention/Treatment
Experimental: Orteronel + prednisone

Drug: Orteronel
Orteronel will be administered orally twice a day continuously throughout the study. Patients will also receive concomitant gonadotropin-releasing hormone (GnRH) analogue therapy unless they have previously undergone orchiectomy and have a testosterone concentration of <50 ng/dL.

Drug: Prednisone
Prednisone will be administered orally twice a day continuously throughout the study. Patients will also receive concomitant gonadotropin-releasing hormone (GnRH) analogue therapy unless they have previously undergone orchiectomy and have a testosterone concentration of <50 ng/dL.
Placebo Comparator: Placebo + prednisone

Drug: Placebo
Placebo will be administered orally twice a day continuously throughout the study. Additionally, all patients will receive concomitant gonadotropin-releasing hormone (GnRH) analogue therapy unless they have previously undergone orchiectomy and a testosterone concentration of <50 ng/dL.

Drug: Prednisone
Prednisone will be administered orally twice a day continuously throughout the study. Patients will also receive concomitant gonadotropin-releasing hormone (GnRH) analogue therapy unless they have previously undergone orchiectomy and have a testosterone concentration of <50 ng/dL.

Outcome Measures

Primary Outcome Measures

  1. Radiographic Progression-free Survival (rPFS) [Baseline until radiographic disease progression or death, whichever occurred first (approximately up to 4.7 years)]

    rPFS 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, whichever occurred first. Radiographic disease progression was evaluated by computerized tomography (CT) scan or magnetic resonance imaging (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 Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 for soft tissue disease and Prostate Cancer Working Group (PCWG2) guidelines for bone disease. Participants who did not reach the endpoint were censored at their last assessment.

  2. Overall Survival [Baseline until death (up to 4.7 years)]

    Overall survival was calculated from the date of participant randomization to the date of participant death due to any cause. Participants without documentation of death at time of the analysis were censored as of the date the participant was last known to be alive, or the data cutoff date, whichever was earlier.

Secondary Outcome Measures

  1. Percentage of Participants Achieving 50 Percent Reduction From Baseline in Prostate Specific Antigen (PSA50) Response at Week 12 [Week 12]

    The PSA50 is defined as a decline of at least 50 percent (%) from baseline.

  2. Percentage of Participants With Favorable Circulating Tumor Cell Count (CTC) Levels at Week 12 [Week 12]

    A favorable CTC count was defined as less than <5 counts per 7.5 milliliter (mL) in whole blood. An unfavorable CTC count was defined as greater than or equal to (>=) 5 counts/7.5 mL in whole blood.

  3. Time to Pain Progression [Baseline until End of treatment (EOT) (approximately up to 4.7 years)]

    Time to pain progression was defined as the time from participant randomization to the first assessment date of pain progression. Pain progression was defined as the occurrence of 1 of the following and confirmed by an additional assessment, at least 3 weeks but not more than 5 weeks later: The brief pain inventory-short form (BPI-SF) worst pain score was >=4 with a >=2 point increase over baseline in BPI-SF worst pain score with stable or increased analgesic use; The BPI-SF worst pain score was >=4 but not less than baseline with new or increased (relative to baseline) Step II or Step III analgesic use; The BPI-SF worst pain score was <=3 but not less than baseline with new or increased (relative to baseline) Step III analgesic use. BPI-SF was an 11-item questionnaire, designed to assess severity and impact of pain on daily functions. Total score ranged from 0 to 100 with lower scores being indicative of less pain or pain interference.

  4. Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [Baseline up to 30 days after last dose of study drug (Cycle 61 Day 58)]

  5. Number of Participants With Treatment-emergent Adverse Events Greater Than or Equal to (>=) Grade 3 [Baseline up to 30 days after last dose of study drug (Cycle 61 Day 58)]

    Grade 3 (Severe) events=unacceptable or intolerable events, significantly interrupting usual daily activity, require systemic drug therapy/other treatment. Grade 4 (Life-threatening) events caused participant to be in imminent danger of death. Grade 5 (Death) events=death related to an AE.

  6. Number of Participants With TEAEs Related to Vital Signs [Baseline up to 30 days after last dose of study drug (Cycle 61 Day 58)]

  7. Number of Participants With TEAEs Related to Weight [Baseline up to 30 days after last dose of study drug (Cycle 61 Day 58)]

  8. Number of Participants With Worst Change From Baseline in Eastern Co-operative Oncology Group (ECOG) Performance Status [Baseline until EOT (approximately up to 4.7 years)]

    ECOG assessed participant's performance status on 5 point scale: 0=Fully active/able to carry on all pre-disease activities without restriction; 1=restricted in physically strenuous activity, ambulatory/able to carry out light or sedentary work; 2=ambulatory (>50 percent of waking hours [hrs]), capable of all self care, unable to carry out any work activities; 3=capable of only limited self care, confined to bed/chair >50 percent of waking hrs; 4=completely disabled, cannot carry on any self care, totally confined to bed/chair; 5=dead. Worst change was defined as the worst overall change that occurred in ECOG status at any measured time point during the treatment period.

  9. Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings [Baseline up to EOT (Cycle 61 Day 58)]

  10. Worst Change From Baseline Over Time in Cardiac Ejection Fraction [Baseline up to 30 days or EOT whichever is later (approximately up to Cycle 61 Day 58)]

    Worst change was defined as the worst overall change that occurred in cardiac ejection fraction at any measured time point.

  11. Number of Participants With TEAEs Categorized Into Investigations Related to Chemistry, Hematology or Coagulation [Baseline up to 30 days or EOT whichever is later (approximately up to Cycle 61 Day 58)]

  12. Percentage of Participants With Skeletal Related Events (SRE) [Baseline up to EOT (approximately up to 4.7 years)]

    Skeletal related (SRE) event is defined as a fracture or spinal cord compression or the need for radiation or surgery at the site of a prostate cancer metastatic lesion that is substantiated by radiographic or pathologic evidence.

  13. Time to SRE [Baseline up to EOT (Cycle 61 Day 58)]

    Time to SRE is defined as the time from randomization to SRE, or death due to any cause, whichever comes first. SRE is defined as a fracture or spinal cord compression or the need for radiation or surgery at the site of a prostate cancer metastatic lesion that is substantiated by radiographic or pathologic evidence.

  14. Percentage of Participants Achieving PSA50 Response at Any Time During the Study [Cycle: 4, 7, 10, 13, 16, 19, 22, 25, 28, 31, 34 and 37]

    The PSA50 is defined as a decline of PSA by 50 percent from baseline.

  15. Percentage of Participants Achieving 90 Percent Reduction From Baseline in Prostate Specific Antigen (PSA90 Response) at Week 12 [Week 12]

    The PSA90 is defined as a decline of PSA by 90 percent from baseline.

  16. Percentage of Participants Achieving PSA90 Response at Any Time During the Study [Cycle: 4, 7, 10, 13, 16, 19, 22, 25, 28, 31, 34 and 37]

    The PSA90 is defined as a decline of PSA by 90 percent from baseline.

  17. Time to PSA Progression [Baseline until the final on treatment assessment or until end of short term follow-up following discontinuation of treatment, whichever occurred later (approximately up to 4.7 years)]

    Time to PSA progression was defined as time from randomization to a PSA increase of 25 percent and PSA rise of at least 2 nanogram per milliliter (ng/mL) above the lowest value observed post baseline or, if no PSA decline occurred post baseline, compared to baseline PSA.

  18. Time to Docetaxel Chemotherapy [Baseline until start of docetaxel chemotherapy (up to 4.7 years)]

    Time to docetaxel based chemotherapy is defined as the time from randomization to the start of docetaxel based chemotherapy for prostate cancer, regardless of whether the participant received concurrent orteronel or not. Deaths due to disease progression prior to Docetaxel based chemotherapy were considered as events.

  19. Time to Subsequent Antineoplastic Therapy [Baseline until start of subsequent antineoplastic therapy (up to 4.7 years)]

    Time to subsequent antineoplastic therapy is defined as the time from randomization to the start of any alternate antineoplastic therapy for prostate cancer. Deaths due to disease progression prior to antineoplastic therapy for prostate cancer are considered as events. Otherwise, time to next therapy is censored at the date of death or the last date the participant was known to be alive or the data cutoff date, whichever is earlier.

  20. Percentage of Participants With Objective Response [Baseline until disease progression or death, whichever occurred first (approximately up to 4.7 years)]

    Percentage of participants with objective response based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST 1.1. A CR was defined as the disappearance of all target lesions determined by computerized tomography (CT) or MRI. Any pathological lymph nodes (whether target or non-target) must have had reduction in short axis to <10 millimetre (mm). A PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of longest diameters of non-lymph node lesions and of the short diameter or short axis of lymph nodes.

  21. Time to Deterioration in Global Health Status [Baseline until EOT (approximately up to 4.7 years)]

    Global health status deterioration is defined as a drop greater than 16 points from the baseline assessment, confirmed at least 3 weeks later, on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core Module 30 (EORTC QLQ-C30) index after the score has been linearly transformed to a 0 to 100 scale. EORTC QLQ-C30 consists of 30 questions, where question 1 to 28 can be answered with 1: Not at all, 2: A little, 3: Quite a bit, 4: Very much and question 29 to 30 with 1: Very poor to 7: Excellent. For subscales a high score from 0-100 indicates: high global quality of life, high level of functioning (physical, role, emotional, cognitive, social) or a high level of symptoms (fatigue, nausea, pain, dyspnea, insomnia, appetite loss, constipation, diarrhoea, financial difficulties).

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
Male
Accepts Healthy Volunteers:
No
Inclusion Criteria:
Each patient must meet all of the following inclusion criteria:

  • Voluntary written consent

  • Male patients 18 years or older

  • Histologically or cytologically confirmed diagnosis of prostate adenocarcinoma

  • Radiograph-documented metastatic disease

  • Progressive disease

  • Prior surgical castration or concurrent use of an agent for medical castration

  • Either absence of pain or pain not requiring use of any opioid or narcotic analgesia in the 2 weeks prior to study entry

  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

  • Even if surgically sterilized, patients must practice effective barrier contraception during the entire study treatment and for 4 months after the last dose of study drug, OR abstain from heterosexual intercourse

  • Meet screening laboratory values as specified in protocol

  • Stable medical condition

Exclusion Criteria:

Patients meeting any of the following exclusion criteria are not to be enrolled in the study:

  • Known hypersensitivity to orteronel, prednisone or gonadotropin-releasing hormone (GnRH) analogue

  • Received prior therapy with orteronel, aminoglutethimide, ketoconazole or abiraterone

  • Received antiandrogen therapy within 6 weeks for bicalutamide and 4 weeks for all others prior to first dose of study drug

  • Continuous daily use of oral prednisone or oral dexamethasone for more than 14 days within 3 months prior to study

  • Received prior chemotherapy for prostate cancer with exception of neoadjuvant/adjuvant therapy as part of initial primary treatment for local disease that was completed 2 or more years prior to screening

  • Exposure to radioisotope therapy within 4 weeks of receiving first dose of study drug; exposure to external beam radiation within 2 weeks of start of screening until receiving the first dose of study drug

  • Documented central nervous system metastases

  • Treatment with any investigational compound within 30 days prior to first dose of study drug

  • Current spinal cord compression, bilateral hydronephrosis or current bladder neck outlet obstruction

  • Diagnosis or treatment of another malignancy within 2 years preceding first dose of study drug except nonmelanoma skin cancer or in situ malignancy completely resected

  • Uncontrolled cardiovascular condition as specified in study protocol

  • Known history of human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C

  • Unwilling or unable to comply with protocol

  • Uncontrolled nausea, vomiting or diarrhea

  • Known gastrointestinal disease or procedure that could interfere with oral absorption or tolerance of orteronel

Contacts and Locations

Locations

Site City State Country Postal Code
1 Anchorage Alaska United States
2 Tucson Arizona United States
3 Duarte California United States
4 Highland California United States
5 Orange California United States
6 Sacramento California United States
7 San Francisco California United States
8 Aurora Colorado United States
9 Denver Colorado United States
10 Deerfield Beach Florida United States
11 Fort Myers Florida United States
12 Jacksonville Florida United States
13 Orlando Florida United States
14 Port St Lucie Florida United States
15 Jeffersonville Indiana United States
16 Kansas City Kansas United States
17 New Orleans Louisiana United States
18 Baltimore Maryland United States
19 Boston Massachusetts United States
20 Lansing Michigan United States
21 Duluth Minnesota United States
22 Corinth Mississippi United States
23 Columbia Missouri United States
24 Jefferson City Missouri United States
25 Omaha Nebraska United States
26 Las Vegas Nevada United States
27 Hackensack New Jersey United States
28 East Syracuse New York United States
29 New York New York United States
30 Durham North Carolina United States
31 Raleigh North Carolina United States
32 Kettering Ohio United States
33 Tualatin Oregon United States
34 Hershey Pennsylvania United States
35 Lancaster Pennsylvania United States
36 Philadelphia Pennsylvania United States
37 Piitsburgh Pennsylvania United States
38 Charleston South Carolina United States
39 Columbia South Carolina United States
40 Chattanooga Tennessee United States
41 Nashville Tennessee United States
42 Amarillo Texas United States
43 Bedford Texas United States
44 Dallas Texas United States
45 Denton Texas United States
46 Tyler Texas United States
47 Salt Lake City Utah United States
48 Norfolk Virginia United States
49 Garran Australia
50 Hobart Australia
51 Kurralta Park Australia
52 Nedlands Australia
53 Perth Australia
54 Redcliffe Australia
55 Wodonga Australia
56 Graz Austria
57 Linz Austria
58 Wien Austria
59 Minsk Belarus
60 Edegem Belgium
61 Hasselt Belgium
62 Kortrijk Belgium
63 Leuven Belgium
64 Namur Belgium
65 Bairro Nazare - Salvador Brazil
66 Barretos/sp Brazil
67 Belo Horizonte Brazil
68 Campinas Brazil
69 Caxias Do Sul Brazil
70 Curitiba Brazil
71 Fortaleza/ce Brazil
72 Ijui Brazil
73 Joinville Brazil
74 Lajeado - Rs Brazil
75 Piracicaba - Sp Brazil
76 Porto Alegre- Rs Brazil
77 Porto Alegre/rs Brazil
78 Ribeirao Preto - Sp Brazil
79 Rio de Janeiro Rj Brazil
80 Rio de Janeiro Brazil
81 Santo Andre Brazil
82 Sao Jose Do Rio Preto Brazil
83 Sao Jose Dos Campos Brazil
84 Sao Paulo Brazil
85 Sorocaba - Sp Brazil
86 Plovdiv Bulgaria
87 Sofia Bulgaria
88 Varna Bulgaria
89 Kelowna British Columbia Canada
90 Burlington Ontario Canada
91 Hamilton Ontario Canada
92 London Ontario Canada
93 Owen Sound Ontario Canada
94 Toronto Ontario Canada
95 Montreal Quebec Canada
96 Pointe Claire Quebec Canada
97 Quebec City Quebec Canada
98 Sherbrooke Quebec Canada
99 Las Condes Chile
100 Santiago Chile
101 Temuco Chile
102 Valparaiso Chile
103 Cali Colombia
104 Hradec Kralove Czech Republic
105 Praha 4 Czech Republic
106 Praha 5 Czech Republic
107 Joensuu Finland
108 Oulu Finland
109 Seinajoki Finland
110 Tampere Finland
111 Angers France
112 Bordeaux France
113 Caen France
114 Creteil France
115 La Roche Sur Yon France
116 Lyon France
117 Marseille France
118 Nancy France
119 Nantes France
120 Paris Cedex 13 France
121 Paris Cedex 14 France
122 Paris France
123 Poitiers France
124 Saint-etienne France
125 Villejuif France
126 Braunschweig Germany
127 Dresden Germany
128 Hamburg Germany
129 Hannover Germany
130 Kassel Germany
131 Kempen Germany
132 Nurtingen Germany
133 Tubingen Germany
134 Wuppertal Germany
135 Athens Greece
136 Heraklion Crete Greece
137 Larissa Greece
138 Patras Greece
139 Thessaloniki Greece
140 Kowloon Hong Kong
141 Shatin Hong Kong
142 Dublin Ireland
143 Galway Ireland
144 Haifa Israel
145 Holon Israel
146 Jerusalem Israel
147 Petach Tikva Israel
148 Ramat-gan Israel
149 Tel Aviv Israel
150 Zerifin Israel
151 Aviano Italy
152 Novara Italy
153 Roma Italy
154 Torino Italy
155 Chiba-city Japan
156 Chiba Japan
157 Fukuoka Japan
158 Hamamatsu City Japan
159 Hokkaido Japan
160 Kanazawa Japan
161 Kita-gun Japan
162 Maebashi-city Japan
163 Mito-city Japan
164 Osaka-city Japan
165 Osaka Japan
166 Sakura City Japan
167 Sayama Japan
168 Sendai City Japan
169 Shimizucho Sunto-gun Japan
170 Suntou-gun Japan
171 Tokyo Japan
172 Yamagata City Japan
173 Yokohama City Japan
174 Yufu-city Japan
175 Riga Latvia
176 Kaunas Lithuania
177 Klaipeda Lithuania
178 Vilnius Lithuania
179 Durango Durango Mexico
180 Mexico City Distrito Federal Mexico
181 Zapopan Jalisco Mexico
182 Amsterdam Netherlands
183 Arnhem Netherlands
184 Breda Netherlands
185 Eindhoven Netherlands
186 Heerlen Netherlands
187 Nieuwegein Netherlands
188 Nijmegen Netherlands
189 Rotterdam Netherlands
190 Auckland New Zealand
191 Christchurch New Zealand
192 Dunedin New Zealand
193 Takapuna New Zealand
194 Tauranga New Zealand
195 Lima Peru
196 Bielsko-biala Poland
197 Wroclaw Poland
198 Liepaja Portugal
199 Lisboa Portugal
200 Porto Portugal
201 San Juan Puerto Rico
202 Bucharest Romania
203 Cluj-napoca Romania
204 Moscow Russian Federation
205 St Petersburg Russian Federation
206 Singapore Singapore
207 Nitra Slovakia
208 Presov Slovakia
209 Trencin Slovakia
210 Zilina Slovakia
211 Cape Town South Africa
212 Durban South Africa
213 George South Africa
214 Port Elizabeth South Africa
215 Barcelona Spain
216 La Coruna Spain
217 Madrid Spain
218 Majadahonda Spain
219 Pamplona Spain
220 Sevilla Spain
221 Valencia Spain
222 Goteborg Sweden
223 Stockholm Sweden
224 Uppsala Sweden
225 Aarau Switzerland
226 Lausanne Switzerland
227 Winterthur Switzerland
228 Zurich Switzerland
229 Taichung Taiwan
230 Taipei Taiwan
231 Dnipropetrovsk Ukraine
232 Donetsk Ukraine
233 Kyiv Ukraine
234 Zaporizhzhya Ukraine
235 Aberdeen United Kingdom
236 Belfast United Kingdom
237 Bristol United Kingdom
238 Cottingham United Kingdom
239 Coventry United Kingdom
240 Glasgow United Kingdom
241 London United Kingdom
242 Manchester United Kingdom
243 Northwood United Kingdom
244 Preston United Kingdom
245 Southampton United Kingdom

Sponsors and Collaborators

  • Millennium Pharmaceuticals, Inc.

Investigators

  • Study Director: Medical Monitor, Millennium Pharmaceuticals, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT01193244
Other Study ID Numbers:
  • C21004
  • 2010-018661-35
  • 0991413276
  • 10/H0406/75
  • U1111-1181-0387
First Posted:
Sep 1, 2010
Last Update Posted:
May 17, 2017
Last Verified:
Apr 1, 2017
Studies a U.S. FDA-regulated Drug Product:
Yes
Additional relevant MeSH terms:
Prostatic Neoplasms
Prednisone

Study Results

Participant Flow

Recruitment Details Participants took part in the study at 324 investigative sites in North America, Europe, Australia, Brazil, Chile, Colombia, Hong Kong, Peru, Puerto Rico, Israel, Japan, Mexico, New Zealand, Singapore, South Africa, and Taiwan from 19 October 2010 to 7 April 2016.
Pre-assignment Detail Male participants who were chemotherapy-naive and had metastatic castration-resistant prostate cancer (mCRPC) with documented progressive metastatic disease were enrolled in 1 of 2 treatment groups to receive Orteronel 400 milligram (mg) + Prednisone 5 mg or Placebo + Prednisone 5 mg.
Arm/Group Title Placebo + Prednisone 5 mg Orteronel 400 mg + Prednisone 5 mg
Arm/Group Description Orteronel placebo-matching tablets, orally, twice daily (BID) and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study. Orteronel 400 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study. In Japan, participants were administered with Orteronel 300 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study.
Period Title: Overall Study
STARTED 779 781
Treated 770 784
COMPLETED 391 391
NOT COMPLETED 388 390

Baseline Characteristics

Arm/Group Title Placebo + Prednisone 5 mg Orteronel 400 mg + Prednisone 5 mg Total
Arm/Group Description Orteronel placebo-matching tablets, orally, twice daily (BID) and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study. Orteronel 400 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study. In Japan, participants were administered with Orteronel 300 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study. Total of all reporting groups
Overall Participants 779 781 1560
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]
71.1
(8.19)
70.9
(8.26)
71.0
(8.22)
Sex: Female, Male (Count of Participants)
Female
0
0%
0
0%
0
0%
Male
779
100%
781
100%
1560
100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino
90
11.6%
107
13.7%
197
12.6%
Not Hispanic or Latino
672
86.3%
669
85.7%
1341
86%
Unknown or Not Reported
17
2.2%
5
0.6%
22
1.4%
Race/Ethnicity, Customized (participants) [Number]
American Indian or Alaska Native
10
1.3%
12
1.5%
22
1.4%
Asian
51
6.5%
38
4.9%
89
5.7%
Native Hawaiian or Other Pacific Islander
2
0.3%
1
0.1%
3
0.2%
Black or African American
19
2.4%
25
3.2%
44
2.8%
White
670
86%
685
87.7%
1355
86.9%
Unknown or Not Reported
12
1.5%
3
0.4%
15
1%
Other
15
1.9%
17
2.2%
32
2.1%
Region of Enrollment (participants) [Number]
Canada
22
2.8%
22
2.8%
44
2.8%
United States
147
18.9%
148
19%
295
18.9%
Austria
12
1.5%
12
1.5%
24
1.5%
Belarus
6
0.8%
10
1.3%
16
1%
Belgium
18
2.3%
21
2.7%
39
2.5%
Bulgaria
6
0.8%
6
0.8%
12
0.8%
Croatia
5
0.6%
1
0.1%
6
0.4%
Czech Republic
13
1.7%
18
2.3%
31
2%
Estonia
2
0.3%
4
0.5%
6
0.4%
Finland
9
1.2%
4
0.5%
13
0.8%
France
66
8.5%
55
7%
121
7.8%
Germany
29
3.7%
40
5.1%
69
4.4%
Greece
23
3%
16
2%
39
2.5%
Hungary
3
0.4%
4
0.5%
7
0.4%
Ireland
11
1.4%
13
1.7%
24
1.5%
Italy
10
1.3%
8
1%
18
1.2%
Latvia
12
1.5%
14
1.8%
26
1.7%
Lithuania
19
2.4%
18
2.3%
37
2.4%
Netherlands
35
4.5%
38
4.9%
73
4.7%
Poland
0
0%
4
0.5%
4
0.3%
Portugal
4
0.5%
4
0.5%
8
0.5%
Romania
20
2.6%
13
1.7%
33
2.1%
Slovakia
9
1.2%
11
1.4%
20
1.3%
Spain
14
1.8%
12
1.5%
26
1.7%
Sweden
11
1.4%
6
0.8%
17
1.1%
Switzerland
10
1.3%
8
1%
18
1.2%
Ukraine
25
3.2%
23
2.9%
48
3.1%
United Kingdom
42
5.4%
53
6.8%
95
6.1%
Australia
27
3.5%
27
3.5%
54
3.5%
Brazil
41
5.3%
50
6.4%
91
5.8%
Chile
20
2.6%
20
2.6%
40
2.6%
Colombia
3
0.4%
6
0.8%
9
0.6%
Hong Kong
1
0.1%
3
0.4%
4
0.3%
Israel
14
1.8%
4
0.5%
18
1.2%
Japan
22
2.8%
18
2.3%
40
2.6%
Mexico
7
0.9%
9
1.2%
16
1%
New Zealand
25
3.2%
26
3.3%
51
3.3%
Peru
6
0.8%
10
1.3%
16
1%
Puerto Rico
1
0.1%
1
0.1%
2
0.1%
Singapore
5
0.6%
2
0.3%
7
0.4%
South Africa
6
0.8%
4
0.5%
10
0.6%
Taiwan, Province Of China
12
1.5%
10
1.3%
22
1.4%
Russia
6
0.8%
5
0.6%
11
0.7%
Height (centimeter) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [centimeter]
172.77
(7.485)
173.26
(7.858)
173.02
(7.675)
Weight (kilogram) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilogram]
84.04
(15.846)
85.09
(16.286)
84.57
(16.071)
Body Mass Index (BMI) (kilogram per square meter (kg/m^2)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilogram per square meter (kg/m^2)]
28.09
(4.651)
28.28
(4.730)
28.19
(4.690)

Outcome Measures

1. Primary Outcome
Title Radiographic Progression-free Survival (rPFS)
Description rPFS 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, whichever occurred first. Radiographic disease progression was evaluated by computerized tomography (CT) scan or magnetic resonance imaging (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 Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 for soft tissue disease and Prostate Cancer Working Group (PCWG2) guidelines for bone disease. Participants who did not reach the endpoint were censored at their last assessment.
Time Frame Baseline until radiographic disease progression or death, whichever occurred first (approximately up to 4.7 years)

Outcome Measure Data

Analysis Population Description
ITT population included all participants who were randomized.
Arm/Group Title Placebo + Prednisone 5 mg Orteronel 400 mg + Prednisone 5 mg
Arm/Group Description Orteronel placebo-matching tablets, orally, twice daily (BID) and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study. Orteronel 400 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study. In Japan, participants were administered with Orteronel 300 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study.
Measure Participants 779 781
Median (95% Confidence Interval) [months]
8.7
13.8
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo + Prednisone 5 mg, Orteronel 400 mg + Prednisone 5 mg
Comments Hazard ratio is based on a stratified Cox's proportional hazard regression model with stratification factors of region and radiographic disease progression at baseline with treatment as a factor in the model. A hazard ratio less than (<) 1 indicated better prevention of death in the orteronel group compared to the placebo group. From log-rank test stratified by region and radiographic disease progression at Baseline.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value <0.00001
Comments
Method Log Rank
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.707
Confidence Interval () 95%
0.626 to 0.799
Parameter Dispersion Type:
Value:
Estimation Comments
2. Primary Outcome
Title Overall Survival
Description Overall survival was calculated from the date of participant randomization to the date of participant death due to any cause. Participants without documentation of death at time of the analysis were censored as of the date the participant was last known to be alive, or the data cutoff date, whichever was earlier.
Time Frame Baseline until death (up to 4.7 years)

Outcome Measure Data

Analysis Population Description
ITT population included all participants who were randomized.
Arm/Group Title Placebo + Prednisone 5 mg Orteronel 400 mg + Prednisone 5 mg
Arm/Group Description Orteronel placebo-matching tablets, orally, twice daily (BID) and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study. Orteronel 400 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study. In Japan, participants were administered with Orteronel 300 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study.
Measure Participants 779 781
Median (95% Confidence Interval) [months]
29.5
29.9
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo + Prednisone 5 mg, Orteronel 400 mg + Prednisone 5 mg
Comments Hazard ratio is based on a stratified Cox's proportional hazard regression model with stratification factors of region and radiographic disease progression at baseline with treatment as a factor in the model. A hazard ratio <1 indicated better prevention of death in the orteronel group compared to the placebo group. From log-rank test stratified by region and radiographic disease progression at baseline.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.59755
Comments
Method Log Rank
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.963
Confidence Interval () 95%
0.838 to 1.107
Parameter Dispersion Type:
Value:
Estimation Comments
3. Secondary Outcome
Title Percentage of Participants Achieving 50 Percent Reduction From Baseline in Prostate Specific Antigen (PSA50) Response at Week 12
Description The PSA50 is defined as a decline of at least 50 percent (%) from baseline.
Time Frame Week 12

Outcome Measure Data

Analysis Population Description
ITT population included all participants who were randomized.
Arm/Group Title Placebo + Prednisone 5 mg Orteronel 400 mg + Prednisone 5 mg
Arm/Group Description Orteronel placebo-matching tablets, orally, twice daily (BID) and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study. Orteronel 400 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study. In Japan, participants were administered with Orteronel 300 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study.
Measure Participants 779 781
Number (95% Confidence Interval) [percentage of participants]
24.6
3.2%
42.6
5.5%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo + Prednisone 5 mg, Orteronel 400 mg + Prednisone 5 mg
Comments Logistic regression model with prognostic factors: region; radiographic disease progression at baseline; age; race; baseline Eastern Cooperative Oncology Group (ECOG) score; Gleason score at initial diagnosis; baseline PSA, natural log scale; presence of visceral disease; alkaline phosphatase; lactate dehydrogenase; and hemoglobin. Odds ratio greater than (>)1 favored orteronel. P-values tested for odds ratio equal to 1.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments
Method Regression, Logistic
Comments
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.166
Confidence Interval () 95%
1.724 to 2.721
Parameter Dispersion Type:
Value:
Estimation Comments
4. Secondary Outcome
Title Percentage of Participants With Favorable Circulating Tumor Cell Count (CTC) Levels at Week 12
Description A favorable CTC count was defined as less than <5 counts per 7.5 milliliter (mL) in whole blood. An unfavorable CTC count was defined as greater than or equal to (>=) 5 counts/7.5 mL in whole blood.
Time Frame Week 12

Outcome Measure Data

Analysis Population Description
ITT population included all participants who were randomized.
Arm/Group Title Placebo + Prednisone 5 mg Orteronel 400 mg + Prednisone 5 mg
Arm/Group Description Orteronel placebo-matching tablets, orally, twice daily (BID) and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study. Orteronel 400 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study. In Japan, participants were administered with Orteronel 300 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study.
Measure Participants 779 781
Number (95% Confidence Interval) [percentage of participants]
9.1
1.2%
15.4
2%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo + Prednisone 5 mg, Orteronel 400 mg + Prednisone 5 mg
Comments Logistic regression model with prognostic factors: region; radiographic disease progression at baseline; age; race; baseline ECOG score; Gleason score at initial diagnosis; baseline PSA, natural log scale; presence of visceral disease; alkaline phosphatase; lactate dehydrogenase; and hemoglobin. Odds ratio > 1 favored orteronel. P-values tested for odds ratio equal to 1.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.001
Comments
Method Regression, Logistic
Comments
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.712
Confidence Interval () 95%
1.235 to 2.373
Parameter Dispersion Type:
Value:
Estimation Comments
5. Secondary Outcome
Title Time to Pain Progression
Description Time to pain progression was defined as the time from participant randomization to the first assessment date of pain progression. Pain progression was defined as the occurrence of 1 of the following and confirmed by an additional assessment, at least 3 weeks but not more than 5 weeks later: The brief pain inventory-short form (BPI-SF) worst pain score was >=4 with a >=2 point increase over baseline in BPI-SF worst pain score with stable or increased analgesic use; The BPI-SF worst pain score was >=4 but not less than baseline with new or increased (relative to baseline) Step II or Step III analgesic use; The BPI-SF worst pain score was <=3 but not less than baseline with new or increased (relative to baseline) Step III analgesic use. BPI-SF was an 11-item questionnaire, designed to assess severity and impact of pain on daily functions. Total score ranged from 0 to 100 with lower scores being indicative of less pain or pain interference.
Time Frame Baseline until End of treatment (EOT) (approximately up to 4.7 years)

Outcome Measure Data

Analysis Population Description
ITT population included all participants who were randomized.
Arm/Group Title Placebo + Prednisone 5 mg Orteronel 400 mg + Prednisone 5 mg
Arm/Group Description Orteronel placebo-matching tablets, orally, twice daily (BID) and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study. Orteronel 400 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study. In Japan, participants were administered with Orteronel 300 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study.
Measure Participants 779 781
Median (95% Confidence Interval) [months]
NA
NA
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo + Prednisone 5 mg, Orteronel 400 mg + Prednisone 5 mg
Comments Hazard ratio is based on a stratified Cox's proportional hazard regression model with stratification factors of region and radiographic disease progression at baseline with treatment as a factor in the model. A hazard ratio less than (<) 1 indicated better prevention of death in the orteronel group compared to the placebo group. From log-rank test stratified by region and radiographic disease progression at baseline.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.33906
Comments
Method Log Rank
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.885
Confidence Interval () 95%
0.688 to 1.138
Parameter Dispersion Type:
Value:
Estimation Comments
6. Secondary Outcome
Title Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Description
Time Frame Baseline up to 30 days after last dose of study drug (Cycle 61 Day 58)

Outcome Measure Data

Analysis Population Description
Safety population included all participants who received at least 1 dose of any study drug.
Arm/Group Title Placebo + Prednisone 5 mg Orteronel 400 mg + Prednisone 5 mg
Arm/Group Description Orteronel placebo-matching tablets, orally, twice daily (BID) and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study. Orteronel 400 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study. In Japan, participants were administered with Orteronel 300 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study.
Measure Participants 770 784
TEAE
733
94.1%
769
98.5%
Serious Adverse Events (SAE)
321
41.2%
380
48.7%
7. Secondary Outcome
Title Number of Participants With Treatment-emergent Adverse Events Greater Than or Equal to (>=) Grade 3
Description Grade 3 (Severe) events=unacceptable or intolerable events, significantly interrupting usual daily activity, require systemic drug therapy/other treatment. Grade 4 (Life-threatening) events caused participant to be in imminent danger of death. Grade 5 (Death) events=death related to an AE.
Time Frame Baseline up to 30 days after last dose of study drug (Cycle 61 Day 58)

Outcome Measure Data

Analysis Population Description
Safety population included all participants who received at least 1 dose of any study drug.
Arm/Group Title Placebo + Prednisone 5 mg Orteronel 400 mg + Prednisone 5 mg
Arm/Group Description Orteronel placebo-matching tablets, orally, twice daily (BID) and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study. Orteronel 400 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study. In Japan, participants were administered with Orteronel 300 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study.
Measure Participants 770 784
Grade 3 or higher TEAE
405
52%
537
68.8%
Grade 5 (Death)
78
10%
77
9.9%
8. Secondary Outcome
Title Number of Participants With TEAEs Related to Vital Signs
Description
Time Frame Baseline up to 30 days after last dose of study drug (Cycle 61 Day 58)

Outcome Measure Data

Analysis Population Description
Safety population included all participants who received at least 1 dose of any study drug.
Arm/Group Title Placebo + Prednisone 5 mg Orteronel 400 mg + Prednisone 5 mg
Arm/Group Description Orteronel placebo-matching tablets, orally, twice daily (BID) and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study. Orteronel 400 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study. In Japan, participants were administered with Orteronel 300 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study.
Measure Participants 770 784
Hypertension
76
9.8%
98
12.5%
Pyrexia
26
3.3%
41
5.2%
Hypotension
12
1.5%
26
3.3%
9. Secondary Outcome
Title Number of Participants With TEAEs Related to Weight
Description
Time Frame Baseline up to 30 days after last dose of study drug (Cycle 61 Day 58)

Outcome Measure Data

Analysis Population Description
Safety population included all participants who received at least 1 dose of any study drug.
Arm/Group Title Placebo + Prednisone 5 mg Orteronel 400 mg + Prednisone 5 mg
Arm/Group Description Orteronel placebo-matching tablets, orally, twice daily (BID) and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study. Orteronel 400 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study. In Japan, participants were administered with Orteronel 300 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study.
Measure Participants 770 784
Weight decreased
47
6%
119
15.2%
Weight increased
36
4.6%
10
1.3%
10. Secondary Outcome
Title Number of Participants With Worst Change From Baseline in Eastern Co-operative Oncology Group (ECOG) Performance Status
Description ECOG assessed participant's performance status on 5 point scale: 0=Fully active/able to carry on all pre-disease activities without restriction; 1=restricted in physically strenuous activity, ambulatory/able to carry out light or sedentary work; 2=ambulatory (>50 percent of waking hours [hrs]), capable of all self care, unable to carry out any work activities; 3=capable of only limited self care, confined to bed/chair >50 percent of waking hrs; 4=completely disabled, cannot carry on any self care, totally confined to bed/chair; 5=dead. Worst change was defined as the worst overall change that occurred in ECOG status at any measured time point during the treatment period.
Time Frame Baseline until EOT (approximately up to 4.7 years)

Outcome Measure Data

Analysis Population Description
Safety population where baseline and post-baseline assessments were available. Safety population included all participants who received at least 1 dose of any study drug.
Arm/Group Title Placebo + Prednisone 5 mg Orteronel 400 mg + Prednisone 5 mg
Arm/Group Description Orteronel placebo-matching tablets, orally, twice daily (BID) and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study. Orteronel 400 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study. In Japan, participants were administered with Orteronel 300 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study.
Measure Participants 760 771
Baseline: 0; Overall: 0
251
32.2%
200
25.6%
Baseline: 0; Overall: 1
177
22.7%
237
30.3%
Baseline: 0; Overall: 2
47
6%
66
8.5%
Baseline: 0; Overall: 3
22
2.8%
15
1.9%
Baseline: 0; Overall: 4
7
0.9%
7
0.9%
Baseline: 1; Overall: 0
6
0.8%
6
0.8%
Baseline: 1; Overall: 1
162
20.8%
147
18.8%
Baseline: 1; Overall: 2
57
7.3%
60
7.7%
Baseline: 1; Overall: 3
28
3.6%
26
3.3%
Baseline: 1; Overall: 4
2
0.3%
6
0.8%
Baseline: 2; Overall: 2
1
0.1%
1
0.1%
11. Secondary Outcome
Title Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings
Description
Time Frame Baseline up to EOT (Cycle 61 Day 58)

Outcome Measure Data

Analysis Population Description
Safety population included all participants who received at least 1 dose of any study drug.
Arm/Group Title Placebo + Prednisone 5 mg Orteronel 400 mg + Prednisone 5 mg
Arm/Group Description Orteronel placebo-matching tablets, orally, twice daily (BID) and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study. Orteronel 400 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study. In Japan, participants were administered with Orteronel 300 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study.
Measure Participants 770 784
Number [participants]
130
16.7%
163
20.9%
12. Secondary Outcome
Title Worst Change From Baseline Over Time in Cardiac Ejection Fraction
Description Worst change was defined as the worst overall change that occurred in cardiac ejection fraction at any measured time point.
Time Frame Baseline up to 30 days or EOT whichever is later (approximately up to Cycle 61 Day 58)

Outcome Measure Data

Analysis Population Description
Safety population where baseline and post-baseline assessments were available. Safety population included all participants who received at least 1 dose of any study drug.
Arm/Group Title Placebo + Prednisone 5 mg Orteronel 400 mg + Prednisone 5 mg
Arm/Group Description Orteronel placebo-matching tablets, orally, twice daily (BID) and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study. Orteronel 400 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study. In Japan, participants were administered with Orteronel 300 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study.
Measure Participants 676 670
Mean (Standard Deviation) [percent ejection fraction]
-3.8
(6.93)
-4.8
(7.00)
13. Secondary Outcome
Title Number of Participants With TEAEs Categorized Into Investigations Related to Chemistry, Hematology or Coagulation
Description
Time Frame Baseline up to 30 days or EOT whichever is later (approximately up to Cycle 61 Day 58)

Outcome Measure Data

Analysis Population Description
Safety population included all participants who received at least 1 dose of any study drug.
Arm/Group Title Placebo + Prednisone 5 mg Orteronel 400 mg + Prednisone 5 mg
Arm/Group Description Orteronel placebo-matching tablets, orally, twice daily (BID) and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study. Orteronel 400 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study. In Japan, participants were administered with Orteronel 300 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study.
Measure Participants 770 784
Investigations
215
27.6%
399
51.1%
Blood and lymphatic system disorders
114
14.6%
107
13.7%
Metabolism and nutrition disorders
204
26.2%
336
43%
14. Secondary Outcome
Title Percentage of Participants With Skeletal Related Events (SRE)
Description Skeletal related (SRE) event is defined as a fracture or spinal cord compression or the need for radiation or surgery at the site of a prostate cancer metastatic lesion that is substantiated by radiographic or pathologic evidence.
Time Frame Baseline up to EOT (approximately up to 4.7 years)

Outcome Measure Data

Analysis Population Description
The ITT population included all participants who were randomized.
Arm/Group Title Placebo + Prednisone 5 mg Orteronel 400 mg + Prednisone 5 mg
Arm/Group Description Orteronel placebo-matching tablets, orally, twice daily (BID) and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study. Orteronel 400 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study. In Japan, participants were administered with Orteronel 300 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study.
Measure Participants 779 781
Number (95% Confidence Interval) [percentage of participants]
10.9
1.4%
8.6
1.1%
15. Secondary Outcome
Title Time to SRE
Description Time to SRE is defined as the time from randomization to SRE, or death due to any cause, whichever comes first. SRE is defined as a fracture or spinal cord compression or the need for radiation or surgery at the site of a prostate cancer metastatic lesion that is substantiated by radiographic or pathologic evidence.
Time Frame Baseline up to EOT (Cycle 61 Day 58)

Outcome Measure Data

Analysis Population Description
The ITT population included all participants who were randomized.
Arm/Group Title Placebo + Prednisone 5 mg Orteronel 400 mg + Prednisone 5 mg
Arm/Group Description Orteronel placebo-matching tablets, orally, twice daily (BID) and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study. Orteronel 400 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study. In Japan, participants were administered with Orteronel 300 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study.
Measure Participants 779 781
Median (95% Confidence Interval) [months]
9.0
13.9
16. Secondary Outcome
Title Percentage of Participants Achieving PSA50 Response at Any Time During the Study
Description The PSA50 is defined as a decline of PSA by 50 percent from baseline.
Time Frame Cycle: 4, 7, 10, 13, 16, 19, 22, 25, 28, 31, 34 and 37

Outcome Measure Data

Analysis Population Description
ITT population where baseline and post-baseline assessments were available. The ITT population included all participants who were randomized.
Arm/Group Title Placebo + Prednisone 5 mg Orteronel 400 mg + Prednisone 5 mg
Arm/Group Description Orteronel placebo-matching tablets, orally, twice daily (BID) and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study. Orteronel 400 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study. In Japan, participants were administered with Orteronel 300 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study.
Measure Participants 779 781
Cycle 4 (n= 687, 672)
28.09
3.6%
49.70
6.4%
Cycle 7 (n= 541, 540)
34.94
4.5%
54.81
7%
Cycle 10 (n= 438, 450)
36.99
4.7%
56.00
7.2%
Cycle 13 (n= 344, 382)
37.21
4.8%
53.14
6.8%
Cycle 16 (n= 286, 303)
34.27
4.4%
54.13
6.9%
Cycle 19 (n= 228, 272)
37.72
4.8%
52.94
6.8%
Cycle 22 (n= 184, 211)
33.15
4.3%
54.03
6.9%
Cycle 25 (n= 109, 119)
35.78
4.6%
46.22
5.9%
Cycle 28 (n= 67, 77)
44.78
5.7%
48.05
6.2%
Cycle 31 (n= 35, 39)
34.29
4.4%
48.72
6.2%
Cycle 34 (n= 22, 18)
36.36
4.7%
38.89
5%
Cycle 37 (n= 7, 5)
71.43
9.2%
40.00
5.1%
17. Secondary Outcome
Title Percentage of Participants Achieving 90 Percent Reduction From Baseline in Prostate Specific Antigen (PSA90 Response) at Week 12
Description The PSA90 is defined as a decline of PSA by 90 percent from baseline.
Time Frame Week 12

Outcome Measure Data

Analysis Population Description
ITT population included all participants who were randomized.
Arm/Group Title Placebo + Prednisone 5 mg Orteronel 400 mg + Prednisone 5 mg
Arm/Group Description Orteronel placebo-matching tablets, orally, twice daily (BID) and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study. Orteronel 400 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study. In Japan, participants were administered with Orteronel 300 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study.
Measure Participants 779 781
Number [percentage of participants]
5.4
0.7%
16.7
2.1%
18. Secondary Outcome
Title Percentage of Participants Achieving PSA90 Response at Any Time During the Study
Description The PSA90 is defined as a decline of PSA by 90 percent from baseline.
Time Frame Cycle: 4, 7, 10, 13, 16, 19, 22, 25, 28, 31, 34 and 37

Outcome Measure Data

Analysis Population Description
ITT population where baseline and post-baseline assessments were available. The ITT population included all participants who were randomized.
Arm/Group Title Placebo + Prednisone 5 mg Orteronel 400 mg + Prednisone 5 mg
Arm/Group Description Orteronel placebo-matching tablets, orally, twice daily (BID) and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study. Orteronel 400 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study. In Japan, participants were administered with Orteronel 300 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study.
Measure Participants 779 781
Cycle 4 (n= 687, 672)
5.39
0.7%
16.67
2.1%
Cycle 7 (n= 541, 540)
8.69
1.1%
22.22
2.8%
Cycle 10 (n= 438, 450)
11.64
1.5%
26.44
3.4%
Cycle 13 (n= 344, 382)
12.79
1.6%
26.18
3.4%
Cycle 16 (n= 286, 303)
12.24
1.6%
25.74
3.3%
Cycle 19 (n= 228, 272)
12.72
1.6%
26.10
3.3%
Cycle 22 (n= 184, 211)
10.87
1.4%
28.44
3.6%
Cycle 25 (n= 109, 119)
11.01
1.4%
21.01
2.7%
Cycle 28 (n= 67, 77)
16.42
2.1%
27.27
3.5%
Cycle 31 (n= 35, 39)
8.57
1.1%
12.82
1.6%
Cycle 34 (n= 22, 18)
4.55
0.6%
22.22
2.8%
Cycle 37 (n= 7, 5)
14.29
1.8%
20.00
2.6%
19. Secondary Outcome
Title Time to PSA Progression
Description Time to PSA progression was defined as time from randomization to a PSA increase of 25 percent and PSA rise of at least 2 nanogram per milliliter (ng/mL) above the lowest value observed post baseline or, if no PSA decline occurred post baseline, compared to baseline PSA.
Time Frame Baseline until the final on treatment assessment or until end of short term follow-up following discontinuation of treatment, whichever occurred later (approximately up to 4.7 years)

Outcome Measure Data

Analysis Population Description
ITT population included all participants who were randomized.
Arm/Group Title Placebo + Prednisone 5 mg Orteronel 400 mg + Prednisone 5 mg
Arm/Group Description Orteronel placebo-matching tablets, orally, twice daily (BID) and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study. Orteronel 400 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study. In Japan, participants were administered with Orteronel 300 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study.
Measure Participants 779 781
Median (95% Confidence Interval) [months]
5.59
8.3
20. Secondary Outcome
Title Time to Docetaxel Chemotherapy
Description Time to docetaxel based chemotherapy is defined as the time from randomization to the start of docetaxel based chemotherapy for prostate cancer, regardless of whether the participant received concurrent orteronel or not. Deaths due to disease progression prior to Docetaxel based chemotherapy were considered as events.
Time Frame Baseline until start of docetaxel chemotherapy (up to 4.7 years)

Outcome Measure Data

Analysis Population Description
ITT population included all participants who were randomized.
Arm/Group Title Placebo + Prednisone 5 mg Orteronel 400 mg + Prednisone 5 mg
Arm/Group Description Orteronel placebo-matching tablets, orally, twice daily (BID) and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study. Orteronel 400 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study. In Japan, participants were administered with Orteronel 300 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study.
Measure Participants 779 781
Median (95% Confidence Interval) [months]
19.0
23.0
21. Secondary Outcome
Title Time to Subsequent Antineoplastic Therapy
Description Time to subsequent antineoplastic therapy is defined as the time from randomization to the start of any alternate antineoplastic therapy for prostate cancer. Deaths due to disease progression prior to antineoplastic therapy for prostate cancer are considered as events. Otherwise, time to next therapy is censored at the date of death or the last date the participant was known to be alive or the data cutoff date, whichever is earlier.
Time Frame Baseline until start of subsequent antineoplastic therapy (up to 4.7 years)

Outcome Measure Data

Analysis Population Description
The ITT population included all participants who were randomized.
Arm/Group Title Placebo + Prednisone 5 mg Orteronel 400 mg + Prednisone 5 mg
Arm/Group Description Orteronel placebo-matching tablets, orally, twice daily (BID) and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study. Orteronel 400 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study. In Japan, participants were administered with Orteronel 300 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study.
Measure Participants 779 781
Median (95% Confidence Interval) [months]
13.9
17.2
22. Secondary Outcome
Title Percentage of Participants With Objective Response
Description Percentage of participants with objective response based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST 1.1. A CR was defined as the disappearance of all target lesions determined by computerized tomography (CT) or MRI. Any pathological lymph nodes (whether target or non-target) must have had reduction in short axis to <10 millimetre (mm). A PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of longest diameters of non-lymph node lesions and of the short diameter or short axis of lymph nodes.
Time Frame Baseline until disease progression or death, whichever occurred first (approximately up to 4.7 years)

Outcome Measure Data

Analysis Population Description
The Response Evaluation Criteria in Solid Tumors (RECIST) evaluable population included all participants who had measurable disease by RECIST 1.1 at the baseline assessment.
Arm/Group Title Placebo + Prednisone 5 mg Orteronel 400 mg + Prednisone 5 mg
Arm/Group Description Orteronel placebo-matching tablets, orally, twice daily (BID) and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study. Orteronel 400 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study. In Japan, participants were administered with Orteronel 300 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study.
Measure Participants 243 236
Number (95% Confidence Interval) [percentage of participants]
15.2
2%
34.7
4.4%
23. Secondary Outcome
Title Time to Deterioration in Global Health Status
Description Global health status deterioration is defined as a drop greater than 16 points from the baseline assessment, confirmed at least 3 weeks later, on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core Module 30 (EORTC QLQ-C30) index after the score has been linearly transformed to a 0 to 100 scale. EORTC QLQ-C30 consists of 30 questions, where question 1 to 28 can be answered with 1: Not at all, 2: A little, 3: Quite a bit, 4: Very much and question 29 to 30 with 1: Very poor to 7: Excellent. For subscales a high score from 0-100 indicates: high global quality of life, high level of functioning (physical, role, emotional, cognitive, social) or a high level of symptoms (fatigue, nausea, pain, dyspnea, insomnia, appetite loss, constipation, diarrhoea, financial difficulties).
Time Frame Baseline until EOT (approximately up to 4.7 years)

Outcome Measure Data

Analysis Population Description
The ITT population included all participants who were randomized.
Arm/Group Title Placebo + Prednisone 5 mg Orteronel 400 mg + Prednisone 5 mg
Arm/Group Description Orteronel placebo-matching tablets, orally, twice daily (BID) and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study. Orteronel 400 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study. In Japan, participants were administered with Orteronel 300 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study.
Measure Participants 779 781
Median (95% Confidence Interval) [months]
10.7
8.3

Adverse Events

Time Frame Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to Cycle 61 Day 58).
Adverse Event Reporting Description At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Arm/Group Title Placebo + Prednisone 5 mg Orteronel 400 mg + Prednisone 5 mg
Arm/Group Description Orteronel placebo-matching tablets, orally, twice daily (BID) and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study. Orteronel 400 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study. In Japan, participants were administered with Orteronel 300 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study.
All Cause Mortality
Placebo + Prednisone 5 mg Orteronel 400 mg + Prednisone 5 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total / (NaN) / (NaN)
Serious Adverse Events
Placebo + Prednisone 5 mg Orteronel 400 mg + Prednisone 5 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 321/770 (41.7%) 380/784 (48.5%)
Blood and lymphatic system disorders
Anaemia 18/770 (2.3%) 18/784 (2.3%)
Normochromic normocytic anaemia 1/770 (0.1%) 0/784 (0%)
Febrile neutropenia 2/770 (0.3%) 1/784 (0.1%)
Neutropenia 1/770 (0.1%) 1/784 (0.1%)
Pancytopenia 1/770 (0.1%) 1/784 (0.1%)
Bone marrow failure 0/770 (0%) 1/784 (0.1%)
Lymphadenopathy 0/770 (0%) 1/784 (0.1%)
Thrombocytopenia 4/770 (0.5%) 0/784 (0%)
Cardiac disorders
Acute myocardial infarction 3/770 (0.4%) 7/784 (0.9%)
Myocardial infarction 5/770 (0.6%) 5/784 (0.6%)
Angina pectoris 4/770 (0.5%) 4/784 (0.5%)
Angina unstable 2/770 (0.3%) 2/784 (0.3%)
Acute coronary syndrome 1/770 (0.1%) 2/784 (0.3%)
Myocardial ischaemia 2/770 (0.3%) 1/784 (0.1%)
Stress cardiomyopathy 0/770 (0%) 1/784 (0.1%)
Atrial fibrillation 18/770 (2.3%) 14/784 (1.8%)
Atrial flutter 3/770 (0.4%) 3/784 (0.4%)
Supraventricular tachycardia 0/770 (0%) 3/784 (0.4%)
Atrial tachycardia 0/770 (0%) 2/784 (0.3%)
Cardiac failure 7/770 (0.9%) 8/784 (1%)
Cardiac failure acute 3/770 (0.4%) 2/784 (0.3%)
Cardiac failure congestive 1/770 (0.1%) 2/784 (0.3%)
Cardiogenic shock 0/770 (0%) 2/784 (0.3%)
Cardiopulmonary failure 3/770 (0.4%) 1/784 (0.1%)
Arrhythmia 0/770 (0%) 1/784 (0.1%)
Bradycardia 0/770 (0%) 1/784 (0.1%)
Extrasystoles 0/770 (0%) 1/784 (0.1%)
Tachycardia 0/770 (0%) 1/784 (0.1%)
Cardiac arrest 3/770 (0.4%) 2/784 (0.3%)
Cardio-respiratory arrest 1/770 (0.1%) 1/784 (0.1%)
Coronary artery disease 2/770 (0.3%) 2/784 (0.3%)
Coronary artery stenosis 0/770 (0%) 1/784 (0.1%)
Left ventricular dysfunction 0/770 (0%) 2/784 (0.3%)
Cardiomegaly 0/770 (0%) 1/784 (0.1%)
Ventricular hypertrophy 0/770 (0%) 1/784 (0.1%)
Cardiotoxicity 0/770 (0%) 1/784 (0.1%)
Intracardiac thrombus 1/770 (0.1%) 0/784 (0%)
Mitral valve incompetence 0/770 (0%) 1/784 (0.1%)
Pericardial effusion 0/770 (0%) 1/784 (0.1%)
Atrioventricular block 1/770 (0.1%) 0/784 (0%)
Conduction disorder 1/770 (0.1%) 0/784 (0%)
Ear and labyrinth disorders
Vertigo 2/770 (0.3%) 1/784 (0.1%)
Allergy to arthropod sting 0/770 (0%) 1/784 (0.1%)
Drug hypersensitivity 1/770 (0.1%) 0/784 (0%)
Endocrine disorders
Adrenal insufficiency 0/770 (0%) 4/784 (0.5%)
Adrenocortical insufficiency acute 0/770 (0%) 2/784 (0.3%)
Secondary adrenocortical insufficiency 0/770 (0%) 1/784 (0.1%)
Thyrotoxic crisis 0/770 (0%) 1/784 (0.1%)
Eye disorders
Cataract 2/770 (0.3%) 0/784 (0%)
Optic ischaemic neuropathy 1/770 (0.1%) 0/784 (0%)
Gastrointestinal disorders
Vomiting 6/770 (0.8%) 9/784 (1.1%)
Nausea 3/770 (0.4%) 9/784 (1.1%)
Diarrhoea 5/770 (0.6%) 12/784 (1.5%)
Abdominal pain 2/770 (0.3%) 8/784 (1%)
Abdominal pain lower 0/770 (0%) 2/784 (0.3%)
Pancreatitis acute 0/770 (0%) 5/784 (0.6%)
Pancreatitis 0/770 (0%) 4/784 (0.5%)
Pancreatitis relapsing 0/770 (0%) 1/784 (0.1%)
Constipation 4/770 (0.5%) 7/784 (0.9%)
Gastrointestinal hypomotility 0/770 (0%) 1/784 (0.1%)
Gastrooesophageal reflux disease 1/770 (0.1%) 0/784 (0%)
Ileus 0/770 (0%) 3/784 (0.4%)
Intestinal obstruction 3/770 (0.4%) 1/784 (0.1%)
Gallstone ileus 1/770 (0.1%) 0/784 (0%)
Gastric ulcer 3/770 (0.4%) 1/784 (0.1%)
Gastric ulcer perforation 1/770 (0.1%) 1/784 (0.1%)
Gastric ulcer haemorrhage 0/770 (0%) 1/784 (0.1%)
Mallory-Weiss syndrome 1/770 (0.1%) 2/784 (0.3%)
Gastric haemorrhage 1/770 (0.1%) 1/784 (0.1%)
Oesophageal varices haemorrhage 1/770 (0.1%) 0/784 (0%)
Duodenal ulcer 1/770 (0.1%) 1/784 (0.1%)
Duodenal ulcer haemorrhage 1/770 (0.1%) 1/784 (0.1%)
Duodenal ulcer perforation 1/770 (0.1%) 0/784 (0%)
Intestinal haemorrhage 0/770 (0%) 1/784 (0.1%)
Rectal haemorrhage 0/770 (0%) 1/784 (0.1%)
Large intestinal haemorrhage 1/770 (0.1%) 0/784 (0%)
Food poisoning 0/770 (0%) 2/784 (0.3%)
Duodenitis 0/770 (0%) 1/784 (0.1%)
Enterocolitis 0/770 (0%) 1/784 (0.1%)
Intestinal perforation 0/770 (0%) 1/784 (0.1%)
Large intestine perforation 0/770 (0%) 1/784 (0.1%)
Gastrointestinal haemorrhage 4/770 (0.5%) 1/784 (0.1%)
Small intestinal obstruction 2/770 (0.3%) 1/784 (0.1%)
Inguinal hernia 1/770 (0.1%) 1/784 (0.1%)
Inguinal hernia, obstructive 1/770 (0.1%) 0/784 (0%)
Anal stenosis 0/770 (0%) 1/784 (0.1%)
Large intestine polyp 0/770 (0%) 1/784 (0.1%)
Toothache 0/770 (0%) 1/784 (0.1%)
Dysphagia 0/770 (0%) 1/784 (0.1%)
Diverticular perforation 0/770 (0%) 1/784 (0.1%)
Colitis ischaemic 1/770 (0.1%) 0/784 (0%)
Pancreatic cyst 1/770 (0.1%) 0/784 (0%)
Enterovesical fistula 1/770 (0.1%) 0/784 (0%)
Haemorrhoids 1/770 (0.1%) 0/784 (0%)
Oesophagitis ulcerative 1/770 (0.1%) 0/784 (0%)
Proctitis 1/770 (0.1%) 0/784 (0%)
General disorders
Fatigue 2/770 (0.3%) 11/784 (1.4%)
Asthenia 1/770 (0.1%) 3/784 (0.4%)
Malaise 2/770 (0.3%) 2/784 (0.3%)
General physical health deterioration 6/770 (0.8%) 9/784 (1.1%)
Multi-organ failure 3/770 (0.4%) 3/784 (0.4%)
Multi-organ disorder 1/770 (0.1%) 0/784 (0%)
Performance status decreased 1/770 (0.1%) 0/784 (0%)
Pyrexia 3/770 (0.4%) 6/784 (0.8%)
Non-cardiac chest pain 1/770 (0.1%) 4/784 (0.5%)
Discomfort 0/770 (0%) 1/784 (0.1%)
Chest pain 2/770 (0.3%) 0/784 (0%)
Oedema peripheral 1/770 (0.1%) 2/784 (0.3%)
Face oedema 0/770 (0%) 1/784 (0.1%)
Death 1/770 (0.1%) 0/784 (0%)
Device occlusion 1/770 (0.1%) 0/784 (0%)
Abasia 1/770 (0.1%) 0/784 (0%)
Drug intolerance 1/770 (0.1%) 0/784 (0%)
Hepatobiliary disorders
Drug-induced liver injury 0/770 (0%) 3/784 (0.4%)
Hepatitis toxic 0/770 (0%) 1/784 (0.1%)
Cholecystitis 1/770 (0.1%) 1/784 (0.1%)
Cholecystitis acute 2/770 (0.3%) 0/784 (0%)
Cholelithiasis 1/770 (0.1%) 0/784 (0%)
Hepatic failure 1/770 (0.1%) 0/784 (0%)
Infections and infestations
Pneumonia 9/770 (1.2%) 30/784 (3.8%)
Lobar pneumonia 2/770 (0.3%) 2/784 (0.3%)
Lower respiratory tract infection 1/770 (0.1%) 2/784 (0.3%)
Bronchopneumonia 0/770 (0%) 2/784 (0.3%)
Lung infection 2/770 (0.3%) 1/784 (0.1%)
Bronchitis 1/770 (0.1%) 1/784 (0.1%)
Sepsis 3/770 (0.4%) 12/784 (1.5%)
Urosepsis 4/770 (0.5%) 6/784 (0.8%)
Septic shock 2/770 (0.3%) 3/784 (0.4%)
Bacteraemia 0/770 (0%) 1/784 (0.1%)
Post procedural sepsis 0/770 (0%) 1/784 (0.1%)
Pulmonary sepsis 0/770 (0%) 1/784 (0.1%)
Urinary tract infection 9/770 (1.2%) 13/784 (1.7%)
Pyelonephritis 2/770 (0.3%) 0/784 (0%)
Gastroenteritis 4/770 (0.5%) 3/784 (0.4%)
Appendicitis perforated 0/770 (0%) 2/784 (0.3%)
Diverticulitis 0/770 (0%) 2/784 (0.3%)
Diarrhoea infectious 0/770 (0%) 1/784 (0.1%)
Gastrointestinal infection 0/770 (0%) 1/784 (0.1%)
Cellulitis 2/770 (0.3%) 4/784 (0.5%)
Arthritis bacterial 0/770 (0%) 1/784 (0.1%)
Cellulitis gangrenous 0/770 (0%) 1/784 (0.1%)
Cellulitis of male external genital organ 0/770 (0%) 1/784 (0.1%)
Gangrene 0/770 (0%) 1/784 (0.1%)
Pneumonia bacterial 0/770 (0%) 1/784 (0.1%)
Urinary tract infection bacterial 0/770 (0%) 1/784 (0.1%)
Infection 0/770 (0%) 2/784 (0.3%)
Abscess limb 0/770 (0%) 1/784 (0.1%)
Groin abscess 0/770 (0%) 1/784 (0.1%)
Pelvic abscess 0/770 (0%) 1/784 (0.1%)
Postoperative abscess 1/770 (0.1%) 0/784 (0%)
Respiratory tract infection 1/770 (0.1%) 0/784 (0%)
Erysipelas 2/770 (0.3%) 4/784 (0.5%)
Pneumonia pneumococcal 0/770 (0%) 1/784 (0.1%)
Herpes zoster 1/770 (0.1%) 4/784 (0.5%)
Gastroenteritis viral 2/770 (0.3%) 2/784 (0.3%)
Respiratory tract infection viral 0/770 (0%) 1/784 (0.1%)
Osteomyelitis 0/770 (0%) 3/784 (0.4%)
Intervertebral discitis 0/770 (0%) 1/784 (0.1%)
Bursitis infective 1/770 (0.1%) 0/784 (0%)
Abscess neck 0/770 (0%) 1/784 (0.1%)
Muscle abscess 0/770 (0%) 1/784 (0.1%)
Perineal abscess 1/770 (0.1%) 0/784 (0%)
Diabetic foot infection 0/770 (0%) 1/784 (0.1%)
Skin infection 0/770 (0%) 1/784 (0.1%)
Pilonidal cyst 1/770 (0.1%) 0/784 (0%)
Chronic sinusitis 0/770 (0%) 1/784 (0.1%)
Upper respiratory tract infection 0/770 (0%) 1/784 (0.1%)
Labyrinthitis 0/770 (0%) 1/784 (0.1%)
Fungal oesophagitis 0/770 (0%) 1/784 (0.1%)
Influenza 0/770 (0%) 1/784 (0.1%)
Salmonellosis 0/770 (0%) 1/784 (0.1%)
Borrelia infection 1/770 (0.1%) 0/784 (0%)
Tongue abscess 1/770 (0.1%) 0/784 (0%)
Escherichia urinary tract infection 1/770 (0.1%) 0/784 (0%)
Klebsiella bacteraemia 1/770 (0.1%) 0/784 (0%)
Staphylococcal infection 1/770 (0.1%) 0/784 (0%)
Staphylococcal skin infection 1/770 (0.1%) 0/784 (0%)
Tuberculosis 1/770 (0.1%) 0/784 (0%)
Injury, poisoning and procedural complications
Femoral neck fracture 0/770 (0%) 2/784 (0.3%)
Hip fracture 2/770 (0.3%) 1/784 (0.1%)
Humerus fracture 1/770 (0.1%) 1/784 (0.1%)
Ankle fracture 0/770 (0%) 1/784 (0.1%)
Fibula fracture 0/770 (0%) 1/784 (0.1%)
Forearm fracture 0/770 (0%) 1/784 (0.1%)
Hand fracture 0/770 (0%) 1/784 (0.1%)
Patella fracture 0/770 (0%) 1/784 (0.1%)
Radius fracture 0/770 (0%) 1/784 (0.1%)
Tibia fracture 0/770 (0%) 1/784 (0.1%)
Femur fracture 3/770 (0.4%) 0/784 (0%)
Upper limb fracture 1/770 (0.1%) 0/784 (0%)
Post procedural complication 0/770 (0%) 1/784 (0.1%)
Post procedural fistula 0/770 (0%) 1/784 (0.1%)
Procedural complication 0/770 (0%) 1/784 (0.1%)
Post procedural haematoma 1/770 (0.1%) 0/784 (0%)
Fall 6/770 (0.8%) 3/784 (0.4%)
Skeletal injury 1/770 (0.1%) 0/784 (0%)
Toxicity to various agents 1/770 (0.1%) 3/784 (0.4%)
Spinal compression fracture 0/770 (0%) 2/784 (0.3%)
Spinal fracture 2/770 (0.3%) 0/784 (0%)
Thoracic vertebral fracture 1/770 (0.1%) 0/784 (0%)
Radiation proctitis 0/770 (0%) 2/784 (0.3%)
Cystitis radiation 1/770 (0.1%) 0/784 (0%)
Contusion 1/770 (0.1%) 1/784 (0.1%)
Subdural haematoma 0/770 (0%) 1/784 (0.1%)
Fractured ischium 0/770 (0%) 1/784 (0.1%)
Limb injury 0/770 (0%) 1/784 (0.1%)
Rib fracture 0/770 (0%) 1/784 (0.1%)
Multiple fractures 1/770 (0.1%) 0/784 (0%)
Tendon injury 1/770 (0.1%) 0/784 (0%)
Post procedural pulmonary embolism 1/770 (0.1%) 0/784 (0%)
Urethral stricture postoperative 1/770 (0.1%) 0/784 (0%)
Incisional hernia 0/770 (0%) 1/784 (0.1%)
Investigations
Lipase increased 5/770 (0.6%) 7/784 (0.9%)
Amylase increased 2/770 (0.3%) 2/784 (0.3%)
Pancreatic enzymes increased 0/770 (0%) 1/784 (0.1%)
Aspartate aminotransferase increased 1/770 (0.1%) 2/784 (0.3%)
Alanine aminotransferase increased 0/770 (0%) 2/784 (0.3%)
Gamma-glutamyltransferase increased 0/770 (0%) 2/784 (0.3%)
Hepatic enzyme increased 0/770 (0%) 2/784 (0.3%)
Liver function test abnormal 1/770 (0.1%) 1/784 (0.1%)
Transaminases increased 1/770 (0.1%) 1/784 (0.1%)
Blood creatinine increased 0/770 (0%) 6/784 (0.8%)
Ejection fraction decreased 1/770 (0.1%) 2/784 (0.3%)
International normalised ratio increased 1/770 (0.1%) 2/784 (0.3%)
Blood calcium increased 0/770 (0%) 1/784 (0.1%)
Eastern Cooperative Oncology Group performance status worsened 1/770 (0.1%) 0/784 (0%)
Neutrophil count decreased 1/770 (0.1%) 0/784 (0%)
Metabolism and nutrition disorders
Dehydration 8/770 (1%) 11/784 (1.4%)
Hypovolaemia 0/770 (0%) 1/784 (0.1%)
Diabetes mellitus 2/770 (0.3%) 8/784 (1%)
Diabetes mellitus inadequate control 0/770 (0%) 1/784 (0.1%)
Hyperkalaemia 0/770 (0%) 5/784 (0.6%)
Hypokalaemia 1/770 (0.1%) 1/784 (0.1%)
Hypoglycaemia 0/770 (0%) 6/784 (0.8%)
Decreased appetite 0/770 (0%) 4/784 (0.5%)
Hypocalcaemia 0/770 (0%) 3/784 (0.4%)
Hyperglycaemia 5/770 (0.6%) 2/784 (0.3%)
Hyponatraemia 3/770 (0.4%) 2/784 (0.3%)
Fluid overload 0/770 (0%) 2/784 (0.3%)
Cachexia 2/770 (0.3%) 1/784 (0.1%)
Failure to thrive 2/770 (0.3%) 0/784 (0%)
Diabetic ketoacidosis 2/770 (0.3%) 0/784 (0%)
Musculoskeletal and connective tissue disorders
Back pain 8/770 (1%) 12/784 (1.5%)
Musculoskeletal chest pain 1/770 (0.1%) 2/784 (0.3%)
Pain in extremity 3/770 (0.4%) 1/784 (0.1%)
Flank pain 1/770 (0.1%) 0/784 (0%)
Bone pain 4/770 (0.5%) 6/784 (0.8%)
Spinal pain 1/770 (0.1%) 0/784 (0%)
Osteonecrosis of jaw 2/770 (0.3%) 5/784 (0.6%)
Pathological fracture 8/770 (1%) 3/784 (0.4%)
Arthralgia 2/770 (0.3%) 3/784 (0.4%)
Osteoarthritis 4/770 (0.5%) 1/784 (0.1%)
Intervertebral disc protrusion 1/770 (0.1%) 1/784 (0.1%)
Bursitis 0/770 (0%) 1/784 (0.1%)
Costochondritis 0/770 (0%) 1/784 (0.1%)
Rhabdomyolysis 0/770 (0%) 1/784 (0.1%)
Groin pain 0/770 (0%) 1/784 (0.1%)
Spinal column stenosis 0/770 (0%) 1/784 (0.1%)
Arthropathy 1/770 (0.1%) 0/784 (0%)
Joint destruction 1/770 (0.1%) 0/784 (0%)
Osteoporosis 1/770 (0.1%) 0/784 (0%)
Muscle haemorrhage 1/770 (0.1%) 0/784 (0%)
Muscular weakness 1/770 (0.1%) 0/784 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer 25/770 (3.2%) 24/784 (3.1%)
Prostate cancer metastatic 1/770 (0.1%) 4/784 (0.5%)
Metastatic pain 7/770 (0.9%) 12/784 (1.5%)
Cancer pain 4/770 (0.5%) 2/784 (0.3%)
Oncologic complication 1/770 (0.1%) 0/784 (0%)
Tumour pain 1/770 (0.1%) 0/784 (0%)
Metastases to bone 2/770 (0.3%) 1/784 (0.1%)
Metastases to central nervous system 2/770 (0.3%) 1/784 (0.1%)
Metastases to biliary tract 0/770 (0%) 1/784 (0.1%)
Metastases to bladder 0/770 (0%) 1/784 (0.1%)
Metastases to liver 0/770 (0%) 1/784 (0.1%)
Metastases to small intestine 0/770 (0%) 1/784 (0.1%)
Lymphangiosis carcinomatosa 1/770 (0.1%) 0/784 (0%)
Metastases to lymph nodes 1/770 (0.1%) 0/784 (0%)
Metastases to rectum 1/770 (0.1%) 0/784 (0%)
Metastases to urinary tract 1/770 (0.1%) 0/784 (0%)
Bladder cancer 1/770 (0.1%) 2/784 (0.3%)
Bladder cancer recurrent 0/770 (0%) 1/784 (0.1%)
Bladder transitional cell carcinoma 2/770 (0.3%) 0/784 (0%)
Paraneoplastic syndrome 3/770 (0.4%) 2/784 (0.3%)
Squamous cell carcinoma of skin 0/770 (0%) 2/784 (0.3%)
Adenocarcinoma of colon 0/770 (0%) 1/784 (0.1%)
Colon cancer 1/770 (0.1%) 0/784 (0%)
Colorectal adenocarcinoma 1/770 (0.1%) 0/784 (0%)
Colorectal cancer 1/770 (0.1%) 0/784 (0%)
Squamous cell carcinoma 1/770 (0.1%) 1/784 (0.1%)
Lung adenocarcinoma 0/770 (0%) 1/784 (0.1%)
Squamous cell carcinoma of lung 1/770 (0.1%) 0/784 (0%)
Pituitary tumour benign 0/770 (0%) 1/784 (0.1%)
Gallbladder adenocarcinoma 0/770 (0%) 1/784 (0.1%)
Gastric cancer 0/770 (0%) 1/784 (0.1%)
Chronic lymphocytic leukaemia 0/770 (0%) 1/784 (0.1%)
Lip squamous cell carcinoma 0/770 (0%) 1/784 (0.1%)
Pancreatic carcinoma 0/770 (0%) 1/784 (0.1%)
Throat cancer 0/770 (0%) 1/784 (0.1%)
Neuroendocrine carcinoma 1/770 (0.1%) 0/784 (0%)
Hepatic cancer 1/770 (0.1%) 0/784 (0%)
Fibromatosis 1/770 (0.1%) 0/784 (0%)
Nervous system disorders
Cerebrovascular accident 8/770 (1%) 5/784 (0.6%)
Cerebral ischaemia 2/770 (0.3%) 1/784 (0.1%)
Ischaemic stroke 2/770 (0.3%) 1/784 (0.1%)
Ischaemic cerebral infarction 1/770 (0.1%) 1/784 (0.1%)
Cerebral haemorrhage 0/770 (0%) 1/784 (0.1%)
Haemorrhage intracranial 0/770 (0%) 1/784 (0.1%)
Haemorrhagic stroke 0/770 (0%) 1/784 (0.1%)
Cerebellar haemorrhage 1/770 (0.1%) 0/784 (0%)
Cerebral infarction 1/770 (0.1%) 0/784 (0%)
Intraventricular haemorrhage 1/770 (0.1%) 0/784 (0%)
Syncope 5/770 (0.6%) 7/784 (0.9%)
Somnolence 0/770 (0%) 2/784 (0.3%)
Depressed level of consciousness 1/770 (0.1%) 1/784 (0.1%)
Spinal cord compression 11/770 (1.4%) 6/784 (0.8%)
Cauda equina syndrome 0/770 (0%) 1/784 (0.1%)
Radicular pain 0/770 (0%) 1/784 (0.1%)
Nerve root compression 1/770 (0.1%) 0/784 (0%)
Dizziness 1/770 (0.1%) 2/784 (0.3%)
Presyncope 0/770 (0%) 2/784 (0.3%)
Paraplegia 1/770 (0.1%) 1/784 (0.1%)
Hemiplegia 0/770 (0%) 1/784 (0.1%)
Monoplegia 0/770 (0%) 1/784 (0.1%)
Hemiparesis 1/770 (0.1%) 0/784 (0%)
Seizure 0/770 (0%) 3/784 (0.4%)
Transient ischaemic attack 2/770 (0.3%) 2/784 (0.3%)
Polyneuropathy 0/770 (0%) 1/784 (0.1%)
Carotid artery stenosis 0/770 (0%) 1/784 (0.1%)
Nystagmus 0/770 (0%) 1/784 (0.1%)
Headache 0/770 (0%) 1/784 (0.1%)
Peroneal nerve palsy 0/770 (0%) 1/784 (0.1%)
Hypoaesthesia 0/770 (0%) 1/784 (0.1%)
Peripheral motor neuropathy 0/770 (0%) 1/784 (0.1%)
Encephalopathy 2/770 (0.3%) 0/784 (0%)
IIIrd nerve disorder 1/770 (0.1%) 0/784 (0%)
VIth nerve paralysis 1/770 (0.1%) 0/784 (0%)
Parkinson's disease 1/770 (0.1%) 0/784 (0%)
Tremor 1/770 (0.1%) 0/784 (0%)
Psychiatric disorders
Delirium 0/770 (0%) 1/784 (0.1%)
Confusional state 1/770 (0.1%) 0/784 (0%)
Depression 1/770 (0.1%) 0/784 (0%)
Mental status changes 1/770 (0.1%) 0/784 (0%)
Mood disorder due to a general medical condition 1/770 (0.1%) 0/784 (0%)
Renal and urinary disorders
Acute kidney injury 6/770 (0.8%) 9/784 (1.1%)
Renal failure 3/770 (0.4%) 7/784 (0.9%)
Renal impairment 0/770 (0%) 3/784 (0.4%)
Postrenal failure 2/770 (0.3%) 2/784 (0.3%)
Renal injury 1/770 (0.1%) 1/784 (0.1%)
Chronic kidney disease 1/770 (0.1%) 0/784 (0%)
Urinary retention 20/770 (2.6%) 13/784 (1.7%)
Urinary hesitation 0/770 (0%) 1/784 (0.1%)
Bladder tamponade 1/770 (0.1%) 0/784 (0%)
Pollakiuria 1/770 (0.1%) 0/784 (0%)
Haematuria 16/770 (2.1%) 8/784 (1%)
Hydronephrosis 6/770 (0.8%) 5/784 (0.6%)
Obstructive uropathy 2/770 (0.3%) 0/784 (0%)
Urinary tract obstruction 3/770 (0.4%) 3/784 (0.4%)
Ureteric stenosis 1/770 (0.1%) 1/784 (0.1%)
Hydroureter 1/770 (0.1%) 0/784 (0%)
Calculus ureteric 2/770 (0.3%) 1/784 (0.1%)
Bladder outlet obstruction 0/770 (0%) 1/784 (0.1%)
Urinary bladder rupture 1/770 (0.1%) 0/784 (0%)
Nephrolithiasis 0/770 (0%) 1/784 (0.1%)
Renal colic 0/770 (0%) 1/784 (0.1%)
Cystitis noninfective 1/770 (0.1%) 0/784 (0%)
Azotaemia 1/770 (0.1%) 0/784 (0%)
Renal artery thrombosis 1/770 (0.1%) 0/784 (0%)
Urethral stenosis 1/770 (0.1%) 0/784 (0%)
Reproductive system and breast disorders
Prostatic obstruction 1/770 (0.1%) 1/784 (0.1%)
Prostatomegaly 1/770 (0.1%) 0/784 (0%)
Pelvic pain 0/770 (0%) 1/784 (0.1%)
Prostatitis 1/770 (0.1%) 0/784 (0%)
Scrotal oedema 1/770 (0.1%) 0/784 (0%)
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism 23/770 (3%) 27/784 (3.4%)
Dyspnoea 5/770 (0.6%) 7/784 (0.9%)
Dyspnoea exertional 0/770 (0%) 2/784 (0.3%)
Respiratory distress 0/770 (0%) 1/784 (0.1%)
Interstitial lung disease 0/770 (0%) 2/784 (0.3%)
Atelectasis 0/770 (0%) 1/784 (0.1%)
Organising pneumonia 0/770 (0%) 1/784 (0.1%)
Respiratory failure 3/770 (0.4%) 2/784 (0.3%)
Acute respiratory failure 2/770 (0.3%) 1/784 (0.1%)
Chronic obstructive pulmonary disease 2/770 (0.3%) 3/784 (0.4%)
Wheezing 1/770 (0.1%) 0/784 (0%)
Pulmonary oedema 1/770 (0.1%) 2/784 (0.3%)
Acute respiratory distress syndrome 0/770 (0%) 1/784 (0.1%)
Pleural effusion 1/770 (0.1%) 2/784 (0.3%)
Haemothorax 1/770 (0.1%) 0/784 (0%)
Pneumothorax 1/770 (0.1%) 0/784 (0%)
Pneumonitis 0/770 (0%) 2/784 (0.3%)
Pneumonia aspiration 1/770 (0.1%) 0/784 (0%)
Hypoxia 0/770 (0%) 2/784 (0.3%)
Epistaxis 1/770 (0.1%) 1/784 (0.1%)
Lung disorder 1/770 (0.1%) 1/784 (0.1%)
Pharyngeal pouch 0/770 (0%) 1/784 (0.1%)
Skin and subcutaneous tissue disorders
Rash maculo-papular 0/770 (0%) 1/784 (0.1%)
Urticaria 0/770 (0%) 1/784 (0.1%)
Vascular disorders
Deep vein thrombosis 5/770 (0.6%) 9/784 (1.1%)
Peripheral artery thrombosis 1/770 (0.1%) 0/784 (0%)
Orthostatic hypotension 1/770 (0.1%) 3/784 (0.4%)
Hypotension 1/770 (0.1%) 1/784 (0.1%)
Hypertension 0/770 (0%) 4/784 (0.5%)
Hypovolaemic shock 0/770 (0%) 2/784 (0.3%)
Shock 0/770 (0%) 1/784 (0.1%)
Peripheral ischaemia 0/770 (0%) 2/784 (0.3%)
Femoral artery occlusion 1/770 (0.1%) 0/784 (0%)
Flushing 0/770 (0%) 1/784 (0.1%)
Peripheral vascular disorder 0/770 (0%) 1/784 (0.1%)
Aortic stenosis 2/770 (0.3%) 1/784 (0.1%)
Aortic aneurysm rupture 1/770 (0.1%) 1/784 (0.1%)
Hypertensive crisis 0/770 (0%) 1/784 (0.1%)
Haematoma 0/770 (0%) 1/784 (0.1%)
Venous thrombosis 0/770 (0%) 1/784 (0.1%)
Phlebitis 0/770 (0%) 1/784 (0.1%)
Lymphoedema 1/770 (0.1%) 0/784 (0%)
Other (Not Including Serious) Adverse Events
Placebo + Prednisone 5 mg Orteronel 400 mg + Prednisone 5 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 721/770 (93.6%) 757/784 (96.6%)
Blood and lymphatic system disorders
Anaemia 90/770 (11.7%) 75/784 (9.6%)
Gastrointestinal disorders
Nausea 130/770 (16.9%) 281/784 (35.8%)
Constipation 129/770 (16.8%) 261/784 (33.3%)
Diarrhoea 110/770 (14.3%) 221/784 (28.2%)
Vomiting 115/770 (14.9%) 174/784 (22.2%)
Abdominal pain 40/770 (5.2%) 72/784 (9.2%)
Dyspepsia 33/770 (4.3%) 60/784 (7.7%)
Abdominal pain upper 39/770 (5.1%) 51/784 (6.5%)
General disorders
Fatigue 173/770 (22.5%) 269/784 (34.3%)
Asthenia 70/770 (9.1%) 106/784 (13.5%)
Oedema peripheral 85/770 (11%) 86/784 (11%)
Infections and infestations
Urinary tract infection 60/770 (7.8%) 58/784 (7.4%)
Injury, poisoning and procedural complications
Fall 47/770 (6.1%) 57/784 (7.3%)
Investigations
Lipase increased 35/770 (4.5%) 179/784 (22.8%)
Weight decreased 54/770 (7%) 124/784 (15.8%)
Amylase increased 27/770 (3.5%) 146/784 (18.6%)
Blood creatinine increased 21/770 (2.7%) 78/784 (9.9%)
Alanine aminotransferase increased 14/770 (1.8%) 49/784 (6.3%)
Metabolism and nutrition disorders
Decreased appetite 86/770 (11.2%) 170/784 (21.7%)
Diabetes mellitus 23/770 (3%) 45/784 (5.7%)
Hyperkalaemia 15/770 (1.9%) 47/784 (6%)
Dehydration 18/770 (2.3%) 42/784 (5.4%)
Musculoskeletal and connective tissue disorders
Back pain 196/770 (25.5%) 158/784 (20.2%)
Muscle spasms 118/770 (15.3%) 171/784 (21.8%)
Arthralgia 122/770 (15.8%) 123/784 (15.7%)
Pain in extremity 93/770 (12.1%) 79/784 (10.1%)
Bone pain 75/770 (9.7%) 65/784 (8.3%)
Musculoskeletal pain 64/770 (8.3%) 55/784 (7%)
Musculoskeletal chest pain 42/770 (5.5%) 51/784 (6.5%)
Muscular weakness 42/770 (5.5%) 42/784 (5.4%)
Myalgia 39/770 (5.1%) 45/784 (5.7%)
Nervous system disorders
Dizziness 50/770 (6.5%) 105/784 (13.4%)
Headache 50/770 (6.5%) 70/784 (8.9%)
Dysgeusia 15/770 (1.9%) 46/784 (5.9%)
Psychiatric disorders
Insomnia 65/770 (8.4%) 84/784 (10.7%)
Depression 23/770 (3%) 56/784 (7.1%)
Renal and urinary disorders
Haematuria 45/770 (5.8%) 43/784 (5.5%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea 41/770 (5.3%) 84/784 (10.7%)
Cough 58/770 (7.5%) 62/784 (7.9%)
Dyspnoea exertional 22/770 (2.9%) 41/784 (5.2%)
Vascular disorders
Hypertension 80/770 (10.4%) 98/784 (12.5%)
Hot flush 77/770 (10%) 81/784 (10.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

In general, Investigators may publish clinical data after the earlier of (i) publication by the Sponsor or (ii) 12 months following the abandonment, early termination or database lock; provided a copy of the publication provided to Sponsor at least 30 days ahead of publication, the Sponsor's confidential information is removed as may be requested by Sponsor and Investigator defers publication for up to 60 days in the event Sponsor provides notice that it intends to file a patent application.

Results Point of Contact

Name/Title Medical Director
Organization Takeda
Phone +1-877-825-3327
Email trialdisclosures@takeda.com
Responsible Party:
Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT01193244
Other Study ID Numbers:
  • C21004
  • 2010-018661-35
  • 0991413276
  • 10/H0406/75
  • U1111-1181-0387
First Posted:
Sep 1, 2010
Last Update Posted:
May 17, 2017
Last Verified:
Apr 1, 2017