Trial Outcomes & Findings for Study Comparing Orteronel Plus Prednisone in Participants With Metastatic Castration-Resistant Prostate Cancer. (NCT NCT01193257)

NCT ID: NCT01193257

Last Updated: 2018-12-19

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1099 participants

Primary outcome timeframe

Baseline until death (approximately up to 4.5 years)

Results posted on

2018-12-19

Participant Flow

Participants took part in the study at 260 investigative sites in North America, Europe, Argentina, Australia, Brazil, Chile, China, Colombia, Israel, Japan, Mexico, New Zealand, Singapore, South Africa, South Korea, and Taiwan from 15 November 2010 to 29 February 2016.

Male participants with a historical diagnosis of metastatic-castration resistant prostate cancer (mCRPC) that has progressed during or following docetaxel-based therapy were enrolled in 1 of 2 treatment groups: Orteronel 400 mg + Prednisone 5 mg or Placebo + Prednisone 5 mg.

Participant milestones

Participant milestones
Measure	Placebo + Prednisone Orteronel placebo-matching tablets, orally, twice daily (BID) and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.	Orteronel + Prednisone Orteronel 400 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study. In Japan only, participants were administered with orteronel 300 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.
Overall Study STARTED	365	734
Overall Study Treated	363	732
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	365	734

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo + Prednisone Orteronel placebo-matching tablets, orally, twice daily (BID) and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.	Orteronel + Prednisone Orteronel 400 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study. In Japan only, participants were administered with orteronel 300 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.
Overall Study Death	202	391
Overall Study Study termination by sponsor	0	3
Overall Study Withdrawal by Subject	26	86
Overall Study Lost to Follow-up	2	3
Overall Study Unblinded due to futility	135	251

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo + Prednisone n=365 Participants Orteronel placebo-matching tablets, orally, twice daily (BID) and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.	Orteronel + Prednisone n=734 Participants Orteronel 400 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study. In Japan only, participants were administered with orteronel 300 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.	Total n=1099 Participants Total of all reporting groups
Age, Continuous	69.4 years STANDARD_DEVIATION 7.95 • n=5 Participants	69.2 years STANDARD_DEVIATION 7.82 • n=7 Participants	69.3 years STANDARD_DEVIATION 7.86 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	365 Participants n=5 Participants	734 Participants n=7 Participants	1099 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	45 Participants n=5 Participants	107 Participants n=7 Participants	152 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	302 Participants n=5 Participants	588 Participants n=7 Participants	890 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	18 Participants n=5 Participants	39 Participants n=7 Participants	57 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	1 participants n=5 Participants	4 participants n=7 Participants	5 participants n=5 Participants
Race/Ethnicity, Customized Asian	48 participants n=5 Participants	77 participants n=7 Participants	125 participants n=5 Participants
Race/Ethnicity, Customized Black or African American	9 participants n=5 Participants	18 participants n=7 Participants	27 participants n=5 Participants
Race/Ethnicity, Customized White	305 participants n=5 Participants	620 participants n=7 Participants	925 participants n=5 Participants
Race/Ethnicity, Customized Unknown or Not Reported	1 participants n=5 Participants	3 participants n=7 Participants	4 participants n=5 Participants
Race/Ethnicity, Customized Other	1 participants n=5 Participants	12 participants n=7 Participants	13 participants n=5 Participants
Region of Enrollment Canada	11 participants n=5 Participants	21 participants n=7 Participants	32 participants n=5 Participants
Region of Enrollment United States	26 participants n=5 Participants	54 participants n=7 Participants	80 participants n=5 Participants
Region of Enrollment Austria	5 participants n=5 Participants	14 participants n=7 Participants	19 participants n=5 Participants
Region of Enrollment Belarus	6 participants n=5 Participants	4 participants n=7 Participants	10 participants n=5 Participants
Region of Enrollment Belgium	1 participants n=5 Participants	12 participants n=7 Participants	13 participants n=5 Participants
Region of Enrollment Bulgaria	1 participants n=5 Participants	3 participants n=7 Participants	4 participants n=5 Participants
Region of Enrollment Estonia	3 participants n=5 Participants	2 participants n=7 Participants	5 participants n=5 Participants
Region of Enrollment Finland	4 participants n=5 Participants	7 participants n=7 Participants	11 participants n=5 Participants
Region of Enrollment France	35 participants n=5 Participants	44 participants n=7 Participants	79 participants n=5 Participants
Region of Enrollment Germany	11 participants n=5 Participants	35 participants n=7 Participants	46 participants n=5 Participants
Region of Enrollment Greece	22 participants n=5 Participants	38 participants n=7 Participants	60 participants n=5 Participants
Region of Enrollment Hungary	2 participants n=5 Participants	7 participants n=7 Participants	9 participants n=5 Participants
Region of Enrollment Ireland	3 participants n=5 Participants	6 participants n=7 Participants	9 participants n=5 Participants
Region of Enrollment Italy	7 participants n=5 Participants	14 participants n=7 Participants	21 participants n=5 Participants
Region of Enrollment Portugal	8 participants n=5 Participants	8 participants n=7 Participants	16 participants n=5 Participants
Region of Enrollment Romania	0 participants n=5 Participants	12 participants n=7 Participants	12 participants n=5 Participants
Region of Enrollment Croatia	0 participants n=5 Participants	3 participants n=7 Participants	3 participants n=5 Participants
Region of Enrollment Czech Republic	1 participants n=5 Participants	1 participants n=7 Participants	2 participants n=5 Participants
Region of Enrollment Lithuania	9 participants n=5 Participants	22 participants n=7 Participants	31 participants n=5 Participants
Region of Enrollment Netherlands	6 participants n=5 Participants	12 participants n=7 Participants	18 participants n=5 Participants
Region of Enrollment Poland	5 participants n=5 Participants	17 participants n=7 Participants	22 participants n=5 Participants
Region of Enrollment Russia	2 participants n=5 Participants	2 participants n=7 Participants	4 participants n=5 Participants
Region of Enrollment Serbia	1 participants n=5 Participants	3 participants n=7 Participants	4 participants n=5 Participants
Region of Enrollment Slovakia	5 participants n=5 Participants	10 participants n=7 Participants	15 participants n=5 Participants
Region of Enrollment Spain	16 participants n=5 Participants	25 participants n=7 Participants	41 participants n=5 Participants
Region of Enrollment Sweden	10 participants n=5 Participants	16 participants n=7 Participants	26 participants n=5 Participants
Region of Enrollment Switzerland	1 participants n=5 Participants	2 participants n=7 Participants	3 participants n=5 Participants
Region of Enrollment United Kingdom	32 participants n=5 Participants	75 participants n=7 Participants	107 participants n=5 Participants
Region of Enrollment Argentina	1 participants n=5 Participants	8 participants n=7 Participants	9 participants n=5 Participants
Region of Enrollment Australia	28 participants n=5 Participants	66 participants n=7 Participants	94 participants n=5 Participants
Region of Enrollment Brazil	37 participants n=5 Participants	82 participants n=7 Participants	119 participants n=5 Participants
Region of Enrollment Chile	5 participants n=5 Participants	7 participants n=7 Participants	12 participants n=5 Participants
Region of Enrollment China	5 participants n=5 Participants	6 participants n=7 Participants	11 participants n=5 Participants
Region of Enrollment Colombia	0 participants n=5 Participants	4 participants n=7 Participants	4 participants n=5 Participants
Region of Enrollment Israel	5 participants n=5 Participants	9 participants n=7 Participants	14 participants n=5 Participants
Region of Enrollment Japan	17 participants n=5 Participants	33 participants n=7 Participants	50 participants n=5 Participants
Region of Enrollment Mexico	1 participants n=5 Participants	4 participants n=7 Participants	5 participants n=5 Participants
Region of Enrollment New Zealand	6 participants n=5 Participants	6 participants n=7 Participants	12 participants n=5 Participants
Region of Enrollment Singapore	1 participants n=5 Participants	1 participants n=7 Participants	2 participants n=5 Participants
Region of Enrollment South Africa	4 participants n=5 Participants	14 participants n=7 Participants	18 participants n=5 Participants
Region of Enrollment Taiwan, Province Of China	7 participants n=5 Participants	7 participants n=7 Participants	14 participants n=5 Participants
Region of Enrollment Korea, Republic Of	15 participants n=5 Participants	18 participants n=7 Participants	33 participants n=5 Participants
Height	171.33 centimeter (cm) STANDARD_DEVIATION 7.675 • n=5 Participants	172.52 centimeter (cm) STANDARD_DEVIATION 7.156 • n=7 Participants	172.12 centimeter (cm) STANDARD_DEVIATION 7.350 • n=5 Participants
Weight	79.85 kilogram (kg) STANDARD_DEVIATION 15.183 • n=5 Participants	82.77 kilogram (kg) STANDARD_DEVIATION 15.200 • n=7 Participants	81.80 kilogram (kg) STANDARD_DEVIATION 15.249 • n=5 Participants
Body mass index (BMI)	27.14 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 4.491 • n=5 Participants	27.73 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 4.370 • n=7 Participants	27.54 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 4.418 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline until death (approximately up to 4.5 years)

Population: ITT population included all participants who were randomized.

Outcome measures

Outcome measures
Measure	Placebo + Prednisone n=365 Participants Orteronel placebo-matching tablets, orally, twice daily (BID) and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.	Orteronel + Prednisone n=734 Participants Orteronel 400 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study. In Japan only, participants were administered with orteronel 300 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.
Overall Survival	15.3 months Interval 13.48 to 16.86	17.1 months Interval 15.45 to 18.67

SECONDARY outcome

Timeframe: Baseline until disease progression or death, whichever occurred first (approximately up to 4.5 years)

Population: ITT population included all participants who were randomized.

rPFS was defined as the time from randomization until radiographic disease progression or death due to any cause, whichever occurred first. Radiographic disease progression was defined as the occurrence of 1 or more of the following: The appearance of 2 or more new lesions on radionuclide bone scan as defined by prostate cancer working group (PCWG)2; Should 2 or more new bone lesions be evident at the first assessment (8-week assessment) on treatment, 2 or more additional new lesions must have been evident on a confirmatory assessment at least 6 weeks later; One or more new soft tissue/visceral organ lesions identified by computed tomography (CT)/magnetic resonance imaging (MRI); Progression as defined by response evaluation criteria in solid tumors (RECIST) 1.1 criteria.

Outcome measures

Outcome measures
Measure	Placebo + Prednisone n=365 Participants Orteronel placebo-matching tablets, orally, twice daily (BID) and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.	Orteronel + Prednisone n=734 Participants Orteronel 400 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study. In Japan only, participants were administered with orteronel 300 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.
Radiographic Progression-free Survival (rPFS)	5.7 months Interval 5.46 to 6.97	8.3 months Interval 7.76 to 8.48

SECONDARY outcome

Timeframe: Week 12

Population: ITT population included all participants who were randomized.

The PSA50 was defined as the percentage of participants who had a PSA decline of at least 50 percent (%) from baseline.

Outcome measures

Outcome measures
Measure	Placebo + Prednisone n=365 Participants Orteronel placebo-matching tablets, orally, twice daily (BID) and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.	Orteronel + Prednisone n=734 Participants Orteronel 400 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study. In Japan only, participants were administered with orteronel 300 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.
Percentage of Participants Achieving 50 Percent Reduction From Baseline in Prostate Specific Antigen (PSA50 Response) at Week 12	9.9 percentage of participants	24.9 percentage of participants

SECONDARY outcome

Timeframe: Week 12

Population: ITT population included all participants who were randomized.

Pain response 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: A greater than or equal to (\>=) 2 point reduction from baseline in BPI-SF worst pain score without an increase in analgesic use; or a 25 percent (%) or more reduction in analgesic use from baseline without an increase in worst pain score from baseline.

Outcome measures

Outcome measures
Measure	Placebo + Prednisone n=365 Participants Orteronel placebo-matching tablets, orally, twice daily (BID) and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.	Orteronel + Prednisone n=734 Participants Orteronel 400 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study. In Japan only, participants were administered with orteronel 300 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.
Percentage of Participants With Pain Response at Week 12	9.0 percentage of participants	12.1 percentage of participants

SECONDARY outcome

Timeframe: Baseline up to 30 days after last dose of study drug (Cycle 59 Day 58)

Population: Safety population included all participants who received at least 1 dose of any study drug.

Outcome measures

Outcome measures
Measure	Placebo + Prednisone n=363 Participants Orteronel placebo-matching tablets, orally, twice daily (BID) and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.	Orteronel + Prednisone n=732 Participants Orteronel 400 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study. In Japan only, participants were administered with orteronel 300 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.
Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)	345 participants	719 participants

SECONDARY outcome

Timeframe: Baseline up to 30 days after last dose of study drug (Cycle 59 Day 58)

Population: Safety population included all participants who received at least 1 dose of any study drug.

Outcome measures

Outcome measures
Measure	Placebo + Prednisone n=363 Participants Orteronel placebo-matching tablets, orally, twice daily (BID) and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.	Orteronel + Prednisone n=732 Participants Orteronel 400 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study. In Japan only, participants were administered with orteronel 300 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.
Number of Participants With Abnormal Physical Examination Findings	0 participants	1 participants

SECONDARY outcome

Timeframe: Baseline up to 30 days after last dose of study drug (Cycle 59 Day 58)

Population: Safety population included all participants who received at least 1 dose of any study drug.

Outcome measures

Outcome measures
Measure	Placebo + Prednisone n=363 Participants Orteronel placebo-matching tablets, orally, twice daily (BID) and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.	Orteronel + Prednisone n=732 Participants Orteronel 400 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study. In Japan only, participants were administered with orteronel 300 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.
Number of Participants With TEAEs Related to Vital Signs Hypertension	21 participants	83 participants
Number of Participants With TEAEs Related to Vital Signs Hypotension	8 participants	31 participants
Number of Participants With TEAEs Related to Vital Signs Pyrexia	18 participants	51 participants

SECONDARY outcome

Timeframe: Baseline up to 30 days after last dose of study drug (Cycle 59 Day 58)

Population: Safety population included all participants who received at least 1 dose of any study drug.

Outcome measures

Outcome measures
Measure	Placebo + Prednisone n=363 Participants Orteronel placebo-matching tablets, orally, twice daily (BID) and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.	Orteronel + Prednisone n=732 Participants Orteronel 400 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study. In Japan only, participants were administered with orteronel 300 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.
Number of Participants With TEAEs Related to Weight Weight decreased	32 participants	107 participants
Number of Participants With TEAEs Related to Weight Weight increased	7 participants	6 participants

SECONDARY outcome

Timeframe: Baseline up to End-of-treatment (EOT) (Cycle 59 Day 58)

Population: 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.

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% 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% 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.

Outcome measures

Outcome measures
Measure	Placebo + Prednisone n=353 Participants Orteronel placebo-matching tablets, orally, twice daily (BID) and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.	Orteronel + Prednisone n=705 Participants Orteronel 400 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study. In Japan only, participants were administered with orteronel 300 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.
Number of Participants With Worst Change From Baseline in Eastern Co-operative Oncology Group (ECOG) Performance Status Baseline: 0; Overall: 0	56 participants	112 participants
Number of Participants With Worst Change From Baseline in Eastern Co-operative Oncology Group (ECOG) Performance Status Baseline: 0; Overall: 1	70 participants	121 participants
Number of Participants With Worst Change From Baseline in Eastern Co-operative Oncology Group (ECOG) Performance Status Baseline: 0; Overall: 2	13 participants	47 participants
Number of Participants With Worst Change From Baseline in Eastern Co-operative Oncology Group (ECOG) Performance Status Baseline: 0; Overall: 3	5 participants	18 participants
Number of Participants With Worst Change From Baseline in Eastern Co-operative Oncology Group (ECOG) Performance Status Baseline: 0; Overall: 4	1 participants	3 participants
Number of Participants With Worst Change From Baseline in Eastern Co-operative Oncology Group (ECOG) Performance Status Baseline: 1; Overall: 0	3 participants	10 participants
Number of Participants With Worst Change From Baseline in Eastern Co-operative Oncology Group (ECOG) Performance Status Baseline: 1; Overall: 1	103 participants	179 participants
Number of Participants With Worst Change From Baseline in Eastern Co-operative Oncology Group (ECOG) Performance Status Baseline: 1; Overall: 2	53 participants	113 participants
Number of Participants With Worst Change From Baseline in Eastern Co-operative Oncology Group (ECOG) Performance Status Baseline: 1; Overall: 3	22 participants	39 participants
Number of Participants With Worst Change From Baseline in Eastern Co-operative Oncology Group (ECOG) Performance Status Baseline: 1; Overall: 4	7 participants	11 participants
Number of Participants With Worst Change From Baseline in Eastern Co-operative Oncology Group (ECOG) Performance Status Baseline: 2; Overall: 1	0 participants	6 participants
Number of Participants With Worst Change From Baseline in Eastern Co-operative Oncology Group (ECOG) Performance Status Baseline: 2; Overall: 2	10 participants	25 participants
Number of Participants With Worst Change From Baseline in Eastern Co-operative Oncology Group (ECOG) Performance Status Baseline: 2; Overall: 3	10 participants	18 participants
Number of Participants With Worst Change From Baseline in Eastern Co-operative Oncology Group (ECOG) Performance Status Baseline: 2; Overall: 4	0 participants	3 participants

SECONDARY outcome

Timeframe: Cycle 59 Day 58

Population: Safety population included all participants who received at least 1 dose of any study drug.

Outcome measures

Outcome measures
Measure	Placebo + Prednisone n=363 Participants Orteronel placebo-matching tablets, orally, twice daily (BID) and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.	Orteronel + Prednisone n=732 Participants Orteronel 400 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study. In Japan only, participants were administered with orteronel 300 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.
Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings	1 participants	3 participants

SECONDARY outcome

Timeframe: Baseline up to 30 days after last dose of study drug (Cycle 59 Day 58)

Population: Safety population included all participants who received at least 1 dose of any study drug.

Outcome measures

Outcome measures
Measure	Placebo + Prednisone n=363 Participants Orteronel placebo-matching tablets, orally, twice daily (BID) and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.	Orteronel + Prednisone n=732 Participants Orteronel 400 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study. In Japan only, participants were administered with orteronel 300 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.
Number of Participants With TEAEs Categorized Into Investigations Related to Chemistry, Hematology or Steroid Hormone Panel Digestive enzymes	9 participants	140 participants
Number of Participants With TEAEs Categorized Into Investigations Related to Chemistry, Hematology or Steroid Hormone Panel Renal function analyses	13 participants	41 participants
Number of Participants With TEAEs Categorized Into Investigations Related to Chemistry, Hematology or Steroid Hormone Panel Liver function analyses	14 participants	38 participants
Number of Participants With TEAEs Categorized Into Investigations Related to Chemistry, Hematology or Steroid Hormone Panel Tissue enzyme analyses NEC	16 participants	30 participants
Number of Participants With TEAEs Categorized Into Investigations Related to Chemistry, Hematology or Steroid Hormone Panel Coagulation and bleeding analyses	1 participants	17 participants
Number of Participants With TEAEs Categorized Into Investigations Related to Chemistry, Hematology or Steroid Hormone Panel Mineral and electrolyte analyses	5 participants	9 participants
Number of Participants With TEAEs Categorized Into Investigations Related to Chemistry, Hematology or Steroid Hormone Panel White blood cell analyses	4 participants	8 participants
Number of Participants With TEAEs Categorized Into Investigations Related to Chemistry, Hematology or Steroid Hormone Panel Carbohydrate tolerance analyses-including diabetes	0 participants	8 participants
Number of Participants With TEAEs Categorized Into Investigations Related to Chemistry, Hematology or Steroid Hormone Panel Urinary tract function analyses NEC	1 participants	5 participants
Number of Participants With TEAEs Categorized Into Investigations Related to Chemistry, Hematology or Steroid Hormone Panel Platelet analyses	3 participants	4 participants
Number of Participants With TEAEs Categorized Into Investigations Related to Chemistry, Hematology or Steroid Hormone Panel Cholesterol analyses	1 participants	4 participants
Number of Participants With TEAEs Categorized Into Investigations Related to Chemistry, Hematology or Steroid Hormone Panel Red blood cell analyses	2 participants	3 participants
Number of Participants With TEAEs Categorized Into Investigations Related to Chemistry, Hematology or Steroid Hormone Panel Protein analyses not elsewhere classified (NEC)	0 participants	3 participants
Number of Participants With TEAEs Categorized Into Investigations Related to Chemistry, Hematology or Steroid Hormone Panel Vascular tests NEC (including blood pressure)	3 participants	2 participants
Number of Participants With TEAEs Categorized Into Investigations Related to Chemistry, Hematology or Steroid Hormone Panel Adrenal cortex tests	0 participants	2 participants
Number of Participants With TEAEs Categorized Into Investigations Related to Chemistry, Hematology or Steroid Hormone Panel Metabolism tests NEC	0 participants	2 participants
Number of Participants With TEAEs Categorized Into Investigations Related to Chemistry, Hematology or Steroid Hormone Panel Skeletal and cardiac muscle analyses	0 participants	2 participants
Number of Participants With TEAEs Categorized Into Investigations Related to Chemistry, Hematology or Steroid Hormone Panel Triglyceride analyses	0 participants	1 participants
Number of Participants With TEAEs Categorized Into Investigations Related to Chemistry, Hematology or Steroid Hormone Panel Urinalysis NEC	0 participants	1 participants
Number of Participants With TEAEs Categorized Into Investigations Related to Chemistry, Hematology or Steroid Hormone Panel Vitamin analyses	0 participants	1 participants

SECONDARY outcome

Timeframe: Cycle: 4, 7, 10, 13, 16, 19, 22, and 25

Population: ITT population where baseline and post-baseline assessments were available. The ITT population included all participants who were randomized.

The PSA50 was defined as the percentage of participants who had a PSA decline of at least 50% from baseline.

Outcome measures

Outcome measures
Measure	Placebo + Prednisone n=365 Participants Orteronel placebo-matching tablets, orally, twice daily (BID) and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.	Orteronel + Prednisone n=734 Participants Orteronel 400 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study. In Japan only, participants were administered with orteronel 300 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.
Percentage of Participants Achieving PSA50 Response at Any Time During the Study Cycle 4 (n= 283; 559)	12.72 participants	32.74 participants
Percentage of Participants Achieving PSA50 Response at Any Time During the Study Cycle 7 (n= 163; 403)	18.40 participants	38.21 participants
Percentage of Participants Achieving PSA50 Response at Any Time During the Study Cycle 10 (n= 102; 267)	22.55 participants	36.70 participants
Percentage of Participants Achieving PSA50 Response at Any Time During the Study Cycle 13 (n= 55; 171)	23.64 participants	40.94 participants
Percentage of Participants Achieving PSA50 Response at Any Time During the Study Cycle 16 (n= 34; 107)	23.53 participants	44.86 participants
Percentage of Participants Achieving PSA50 Response at Any Time During the Study Cycle 19 (n= 24; 68)	20.83 participants	42.65 participants
Percentage of Participants Achieving PSA50 Response at Any Time During the Study Cycle 22 (n= 14; 36)	28.57 participants	52.78 participants
Percentage of Participants Achieving PSA50 Response at Any Time During the Study Cycle 25 (n= 8; 16)	25.00 participants	62.50 participants

SECONDARY outcome

Timeframe: Week 12

Population: ITT population where baseline and post-baseline assessments were available. ITT population included all participants who were randomized.

The PSA90 was defined as the percentage of participants who had a PSA decline of at least 90% from baseline.

Outcome measures

Outcome measures
Measure	Placebo + Prednisone n=283 Participants Orteronel placebo-matching tablets, orally, twice daily (BID) and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.	Orteronel + Prednisone n=559 Participants Orteronel 400 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study. In Japan only, participants were administered with orteronel 300 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.
Percentage of Participants Achieving 90 Percent Reduction From Baseline in Prostate Specific Antigen (PSA90 Response) at Week 12	2.83 percentage of participants	9.66 percentage of participants

SECONDARY outcome

Timeframe: Cycle: 7, 10, 13, 16, 19, 22, and 25

Population: ITT population where baseline and post-baseline assessments were available. ITT population included all participants who were randomized.

The PSA90 was defined as the percentage of participants who had a PSA decline of at least 90% from baseline.

Outcome measures

Outcome measures
Measure	Placebo + Prednisone n=365 Participants Orteronel placebo-matching tablets, orally, twice daily (BID) and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.	Orteronel + Prednisone n=734 Participants Orteronel 400 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study. In Japan only, participants were administered with orteronel 300 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.
Percentage of Participants Achieving PSA90 Response at Any Time During the Study Cycle 7 (n=163; 403)	4.91 percentage of participants	14.89 percentage of participants
Percentage of Participants Achieving PSA90 Response at Any Time During the Study Cycle 10 (n=102; 267)	6.86 percentage of participants	14.23 percentage of participants
Percentage of Participants Achieving PSA90 Response at Any Time During the Study Cycle 13 (n=55; 171)	7.27 percentage of participants	15.20 percentage of participants
Percentage of Participants Achieving PSA90 Response at Any Time During the Study Cycle 16 (n=34; 107)	5.88 percentage of participants	19.63 percentage of participants
Percentage of Participants Achieving PSA90 Response at Any Time During the Study Cycle 19 (n=24; 68)	4.17 percentage of participants	23.53 percentage of participants
Percentage of Participants Achieving PSA90 Response at Any Time During the Study Cycle 22 (n=14; 36)	0.00 percentage of participants	27.78 percentage of participants
Percentage of Participants Achieving PSA90 Response at Any Time During the Study Cycle 25 (n=8; 16)	0.00 percentage of participants	43.75 percentage of participants

SECONDARY outcome

Timeframe: Cycle: 4, 7, 10, 13, 16, 19, 22, and 25

Population: Best PSA response was not evaluated due to change in planned analysis.

The PSA50 was defined as the percentage of participants who had a PSA decline of at least 50% from baseline. PSA90 was defined as the percentage of participants who had a PSA decline of at least 90% from baseline.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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 4.5 years)

Population: ITT population included all participants who were randomized.

Time to PSA progression was defined as time from randomization to a PSA increase of 25% 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, above the baseline PSA.

Outcome measures

Outcome measures
Measure	Placebo + Prednisone n=365 Participants Orteronel placebo-matching tablets, orally, twice daily (BID) and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.	Orteronel + Prednisone n=734 Participants Orteronel 400 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study. In Japan only, participants were administered with orteronel 300 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.
Time to PSA Progression	2.9 months Interval 2.83 to 2.9	5.5 months Interval 4.4 to 5.56

SECONDARY outcome

Timeframe: Baseline and EOT (Cycle 59 Day 58)

Population: ITT population where baseline and post-baseline assessments were available. ITT population included all participants who were randomized.

A favorable CTC count was defined as less than (\<) 5 counts per (/) 7.5 mililiter (mL) in whole blood. An unfavorable CTC count was defined as \>=5 counts/7.5 mL in whole blood.

Outcome measures

Outcome measures
Measure	Placebo + Prednisone n=157 Participants Orteronel placebo-matching tablets, orally, twice daily (BID) and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.	Orteronel + Prednisone n=267 Participants Orteronel 400 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study. In Japan only, participants were administered with orteronel 300 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.
Number of Participants With Shifts From Baseline Between Favorable and Unfavorable Categories in Circulating Tumor Cell Count (CTC) Baseline: Favorable; EOT: Favorable	27 participants	63 participants
Number of Participants With Shifts From Baseline Between Favorable and Unfavorable Categories in Circulating Tumor Cell Count (CTC) Baseline: Favorable; EOT: Unfavorable	30 participants	40 participants
Number of Participants With Shifts From Baseline Between Favorable and Unfavorable Categories in Circulating Tumor Cell Count (CTC) Baseline: Unfavorable; EOT: Favorable	8 participants	23 participants
Number of Participants With Shifts From Baseline Between Favorable and Unfavorable Categories in Circulating Tumor Cell Count (CTC) Baseline: Unfavorable; EOT: Unfavorable	92 participants	141 participants

SECONDARY outcome

Timeframe: Baseline until disease progression or death, whichever occurred first (approximately up to 4.5 years)

Population: Response per RECIST-evaluable population was defined as a subset of participants who had measurable disease by RECIST 1.1 at baseline.

Percentage of participants with objective response based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST 1.1. The overall objective response was defined as a complete response (CR) or partial response (PR). A complete response (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(s) or short axis of lymph nodes.

Outcome measures

Outcome measures
Measure	Placebo + Prednisone n=146 Participants Orteronel placebo-matching tablets, orally, twice daily (BID) and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.	Orteronel + Prednisone n=280 Participants Orteronel 400 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study. In Japan only, participants were administered with orteronel 300 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.
Percentage of Participants With Objective Response	2.7 percentage of participants	17.1 percentage of participants

SECONDARY outcome

Timeframe: Baseline until EOT visit or until end of short term follow-up, whichever occurred later (approximately up to 4.5 years)

Population: ITT population included all participants who were randomized.

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.

Outcome measures

Outcome measures
Measure	Placebo + Prednisone n=365 Participants Orteronel placebo-matching tablets, orally, twice daily (BID) and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.	Orteronel + Prednisone n=734 Participants Orteronel 400 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study. In Japan only, participants were administered with orteronel 300 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.
Time to Pain Progression	22.0 months Interval 20.48 to The upper limit was not estimable.	24.2 months Interval 18.24 to 24.2

SECONDARY outcome

Timeframe: Baseline until disease progression or death, whichever occurred first (approximately up to 4.5 years)

Population: ITT population included all participants who were randomized.

Time to pain response was defined as the time from randomization until first pain response. Pain response 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: A \>= 2 point reduction from baseline in BPI-SF worst pain score without an increase in analgesic use, or a 25% or more reduction in analgesic use from baseline without an increase in worst pain score from baseline. The analysis was performed by Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Placebo + Prednisone n=365 Participants Orteronel placebo-matching tablets, orally, twice daily (BID) and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.	Orteronel + Prednisone n=734 Participants Orteronel 400 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study. In Japan only, participants were administered with orteronel 300 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.
Time to Pain Response	NA months Median: No data is reported since median time to pain response was not estimable (that is, not reached) in either treatment group due to low number of events. Confidence interval: Confidence interval was not estimable due to low number of events	NA months Median: No data is reported since median time to pain response was not estimable (that is, not reached) in either treatment group due to low number of events. Confidence interval: Confidence interval was not estimable due to low number of events

SECONDARY outcome

Timeframe: Baseline until disease progression or death, whichever occurred first (approximately up to 4.5 years)

Population: ITT population included all participants who were randomized.

Best pain response was evaluated in participants who had a pain response across the entire study were summarized by treatment group. The pain response was defined as a \>=2-point reduction from baseline in BPI-SF worst pain score without an increase in analgesic use, or a 25% or more reduction in analgesic use from baseline without an increase in worst pain score from baseline.

Outcome measures

Outcome measures
Measure	Placebo + Prednisone n=365 Participants Orteronel placebo-matching tablets, orally, twice daily (BID) and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.	Orteronel + Prednisone n=734 Participants Orteronel 400 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study. In Japan only, participants were administered with orteronel 300 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.
Number of Participants With Best Pain Response	72 participants	166 participants

SECONDARY outcome

Timeframe: Week 12

Population: ITT population included all participants who were randomized.

The global health status or quality of life (QOL) was measured as the HRQOL response rate at 12 weeks using the 2-item global health status index of the european organization for research and treatment of cancer-quality of life questionnaire-C30 (EORTC QLQ-C30) instrument. HRQOL response was defined as a 17-point increase from the baseline assessment on the QOL index, after the score had been linearly transformed to a 0 to 100 scale. EORTC QLQ-C30: included 5 functional scales (physical, role, cognitive, emotional, and social), 1 global health status, 3 symptom scales (fatigue, pain, nausea/vomiting) and 6 single items (dyspnoea, appetite loss, insomnia, constipation/diarrhea and financial difficulties). Most questions used 4 point scale (1 'Not at all' to 4 'Very much'; 2 questions used 7-point scale (1 'very poor' to 7 'Excellent'). Scores averaged, transformed to 0-100 scale; higher score representing better level of functioning or greater degree of symptoms.

Outcome measures

Outcome measures
Measure	Placebo + Prednisone n=365 Participants Orteronel placebo-matching tablets, orally, twice daily (BID) and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.	Orteronel + Prednisone n=734 Participants Orteronel 400 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study. In Japan only, participants were administered with orteronel 300 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.
Percentage of Participants With Health-related Quality of Life (HRQOL) Response at Week 12	9.9 percentage of participants	8.7 percentage of participants

Adverse Events

Placebo + Prednisone

Serious events: 148 serious events

Other events: 341 other events

Deaths: 0 deaths

Orteronel + Prednisone

Serious events: 384 serious events

Other events: 703 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Director

Takeda

Phone: +1-877-825-3327

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER