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Trial record 91 of 103 for:    "Kennedy disease"

An Asian Study to Evaluate Efficacy and Safety of Oral Enzalutamide in Progressive Metastatic Prostate Cancer Participants

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02294461
Recruitment Status : Active, not recruiting
First Posted : November 19, 2014
Results First Posted : April 12, 2017
Last Update Posted : December 11, 2018
Sponsor:
Information provided by (Responsible Party):
Astellas Pharma Inc

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Progressive Metastatic Prostate Cancer
Interventions Drug: Enzalutamide
Drug: Placebo
Enrollment 388
Recruitment Details The study population consisted of men with asymptomatic or mildly symptomatic progressive metastatic prostate cancer, who had failed androgen deprivation therapy, and have not been treated with cytotoxic chemotherapy. Participants from 46 study sites in 4 countries (China, Korea, Taiwan and Hong Kong) were randomized for the study.
Pre-assignment Details Data cutoff date for the efficacy and safety data is 20 Sept 2015 and for the final PK analysis data cutoff date is 20 Jan 2016. Study completed double-blind period and is now in the open-label period.
Arm/Group Title Enzalutamide Placebo
Hide Arm/Group Description Participants received 160 mg of enzalutamide orally once a day until Prostate-Specific Antigen (PSA) progression and radiographic disease progression were centrally confirmed and 1 of the following 2 events became applicable to the participants: (1) initiation of cytotoxic chemotherapy or (2) initiation of an investigational agent for treatment of prostate cancer. Participants received matching placebo orally once a day until PSA progression and radiographic disease progression were centrally confirmed and 1 of the following 2 events became applicable to the participants: (1) initiation of cytotoxic chemotherapy or (2) initiation of an investigational agent for treatment of prostate cancer.
Period Title: Overall Study
Started 198 190
Treated/Received Study Drug 198 190
Completed 136 [1] 59
Not Completed 62 131
Reason Not Completed
Death             3             3
Protocol Violation             0             2
Withdrawal by Subject             14             45
Disease Progression             23             39
Adverse Event             11             10
Miscellaneous             11             32
[1]
Participants still receiving treatment as of 20 Sept 2016. Data cutoff date: 20 Sep 2015/20 Jan 2016
Arm/Group Title Enzalutamide Placebo Total
Hide Arm/Group Description Participants received 160 mg of enzalutamide orally once a day until Prostate-Specific Antigen (PSA) progression and radiographic disease progression were centrally confirmed and 1 of the following 2 events became applicable to the participants: (1) initiation of cytotoxic chemotherapy or (2) initiation of an investigational agent for treatment of prostate cancer. Participants received matching placebo orally once a day until PSA progression and radiographic disease progression were centrally confirmed and 1 of the following 2 events became applicable to the participants: (1) initiation of cytotoxic chemotherapy or (2) initiation of an investigational agent for treatment of prostate cancer. Total of all reporting groups
Overall Number of Baseline Participants 198 190 388
Hide Baseline Analysis Population Description
Intent-to-treat (ITT) population consisted of all randomized participants in the study. Data cutoff date was 20 Sept 2016.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 198 participants 190 participants 388 participants
71.4  (8.2) 71.0  (8.7) 71.2  (8.4)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 198 participants 190 participants 388 participants
Female
0
   0.0%
0
   0.0%
0
   0.0%
Male
198
 100.0%
190
 100.0%
388
 100.0%
1.Primary Outcome
Title Time to Prostate-specific Antigen (PSA) Progression
Hide Description The time to Prostate Specific Antigen (PSA) progression was defined as the time from randomization to the PSA progression. The PSA progression was defined according to the consensus guidelines of Prostate Cancer Clinical Trials Working Group 2 (PCWG2).For participants with PSA decline at Week 13, the PSA progression date was defined as a ≥ 25% increase and an absolute increase of ≥ 2 ng/mL above the nadir, which would be confirmed by a second consecutive value obtained 3 or more weeks later. For participants with no PSA decline at Week 13, the PSA progression date was defined as the date when a ≥ 25% increase and an absolute increase of ≥ 2 ng/mL above the baseline was documented, which was confirmed by a second consecutive value 3 or more weeks later. PSA progression at the time of the data analysis cutoff date could only be declared on or after week 13. Time to PSA progression was estimated using the Kaplan-Meier method. Participants without confirmed PSA progression were censored.
Time Frame From randomization up to data cut off date of 20 Sept 2015; median follow-up time is 7.33 months for enzalutamide and 3.02 months for placebo
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent-to-Treat (ITT) population consisted of all randomized participants in the study.
Arm/Group Title Enzalutamide Placebo
Hide Arm/Group Description:
Participants received 160 mg of enzalutamide orally once a day until Prostate-Specific Antigen (PSA) progression and radiographic disease progression were centrally confirmed and 1 of the following 2 events became applicable to the participants: (1) initiation of cytotoxic chemotherapy or (2) initiation of an investigational agent for treatment of prostate cancer.
Participants received matching placebo orally once a day until PSA progression and radiographic disease progression were centrally confirmed and 1 of the following 2 events became applicable to the participants: (1) initiation of cytotoxic chemotherapy or (2) initiation of an investigational agent for treatment of prostate cancer.
Overall Number of Participants Analyzed 198 190
Median (95% Confidence Interval)
Unit of Measure: Months
8.31
(5.72 to 10.25)
2.86
(2.83 to 4.63)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Enzalutamide, Placebo
Comments P-value is based on an unstratified log-rank test. Hazard ratio calculated using unstratified Cox Proportional Hazards model with treatment as the only covariate for enzalutamide group versus placebo group.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Hazard Ratio
Comments [Not Specified]
Method of Estimation Estimation Parameter Unstratified Cox Proportional Hazards
Estimated Value 0.38
Confidence Interval (2-Sided) 95%
0.27 to 0.52
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Duration of Overall Survival
Hide Description Duration of overall survival was defined as the time from the randomization to deaths from any cause. For participants who were alive at the time of the data analysis, overall survival time was censored to the last know date the participants were known to be alive or data analysis cutoff date, whichever occurred first.
Time Frame From randomization up to data cutoff date of 20 Sept 2015; median follow-up time is 8.02 months for enzalutamide and 5.55 months for placebo
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent-to-Treat (ITT) population consisted of all randomized participants in the study.
Arm/Group Title Enzalutamide Placebo
Hide Arm/Group Description:
Participants received 160 mg of enzalutamide orally once a day until Prostate-Specific Antigen (PSA) progression and radiographic disease progression were centrally confirmed and 1 of the following 2 events became applicable to the participants: (1) initiation of cytotoxic chemotherapy or (2) initiation of an investigational agent for treatment of prostate cancer.
Participants received matching placebo orally once a day until PSA progression and radiographic disease progression were centrally confirmed and 1 of the following 2 events became applicable to the participants: (1) initiation of cytotoxic chemotherapy or (2) initiation of an investigational agent for treatment of prostate cancer.
Overall Number of Participants Analyzed 198 190
Median (95% Confidence Interval)
Unit of Measure: Months
NA [1] 
(NA to NA)
NA [1] 
(11.70 to NA)
[1]
Could not be estimated due to the low number of events at the time of the data cutoff date.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Enzalutamide, Placebo
Comments Participants who were not known to have had died at the analysis date were censored at date last known alive or data analysis cutoff date, whichever occurred first. Hazard ratio calculated using unstratified Cox Proportional Hazards model with treatment as the only covariate for enzalutamide group versus placebo group.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0015
Comments P-value is based on an unstratified log-rank test.
Method Unstratified log-rank test
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.33
Confidence Interval (2-Sided) 95%
0.16 to 0.67
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Duration of Radiographic Progression-free Survival (rPFS) Based on Independent Central Review Facility Assessment
Hide Description Duration of Radiographic Progression-free Survival (rPFS) was defined as the time from randomization to the rPFS event (deaths from any cause and radiographic disease progression). Radiographic disease progression is defined by RECIST 1.1 for soft tissue disease, or PCWG2 for bone lesions. If a participant met the criteria for more than 1 censoring rule, they were censored with the earliest censoring date. The radiographic progression date was the first date when progression definition was met, not confirmed.
Time Frame From randomization up to data cutoff date of 20 Sept 2015; median follow-up time is 5.55 months for enzalutamide and 3.71 months for placebo
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT) population consisted of all randomized participants in the study.
Arm/Group Title Enzalutamide Placebo
Hide Arm/Group Description:
Participants received 160 mg of enzalutamide orally once a day until Prostate-Specific Antigen (PSA) progression and radiographic disease progression were centrally confirmed and 1 of the following 2 events became applicable to the participants: (1) initiation of cytotoxic chemotherapy or (2) initiation of an investigational agent for treatment of prostate cancer.
Participants received matching placebo orally once a day until PSA progression and radiographic disease progression were centrally confirmed and 1 of the following 2 events became applicable to the participants: (1) initiation of cytotoxic chemotherapy or (2) initiation of an investigational agent for treatment of prostate cancer.
Overall Number of Participants Analyzed 198 190
Median (95% Confidence Interval)
Unit of Measure: Months
NA [1] 
(10.97 to NA)
5.29
(3.61 to 11.33)
[1]
Could not be estimated due to the low number of events at the time of the data cutoff date.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Enzalutamide, Placebo
Comments Participants who were not known to have had an rPFS event at the time of data cutoff were censored at the date of the last assessment showing no objective evidence of rPFS prior to scan modality change, new antineoplastic treatment, initiation of radiation therapy for prostate cancer, skeletal-related event (SRE) and 2 or more consecutive missed tumor assessments. Hazard ratio calculated using unstratified Cox Proportional Hazards model with treatment as the only covariate for enzalutamide.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments P-value is based on an unstratified log-rank test.
Method Unstratified log-rank test
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.31
Confidence Interval 95%
0.20 to 0.46
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Time to First Skeletal-Related Event
Hide Description Time to first skeletal-related event (SRE) was defined as the time from randomization to the first skeletal-related event, defined as radiation therapy or surgery to bone, pathologic bone fracture, spinal cord compression, or change of anti-neoplastic therapy to treat bone pain. Participants who have not had a SRE at the time of the analysis were censored at their last assessment indicating no evidence of SRE.
Time Frame From randomization up to data cutoff date of 20 Sept 2015; median follow-up time is 7.39 months for enzalutamide and 5.29 months for placebo
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent-to-Treat (ITT) population consisted of all randomized participants in the study.
Arm/Group Title Enzalutamide Placebo
Hide Arm/Group Description:
Participants received 160 mg of enzalutamide orally once a day until Prostate-Specific Antigen (PSA) progression and radiographic disease progression were centrally confirmed and 1 of the following 2 events became applicable to the participants: (1) initiation of cytotoxic chemotherapy or (2) initiation of an investigational agent for treatment of prostate cancer.
Participants received matching placebo orally once a day until PSA progression and radiographic disease progression were centrally confirmed and 1 of the following 2 events became applicable to the participants: (1) initiation of cytotoxic chemotherapy or (2) initiation of an investigational agent for treatment of prostate cancer.
Overall Number of Participants Analyzed 198 190
Median (95% Confidence Interval)
Unit of Measure: Months
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
Could not be estimated due to the low number of events at the time of the data cutoff date.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Enzalutamide, Placebo
Comments Participants who did not have an SRE at the time of analysis data cutoff were censored at the date of the last assessment indicating no evidence of SRE. Hazard ratio calculated using unstratified Cox Proportional Hazards model with treatment as the only covariate for enzalutamide group versus placebo group.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2501
Comments P-value was based on an unstratified log-rank test.
Method Unstratified log-rank test
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.56
Confidence Interval (2-Sided) 95%
0.21 to 1.52
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Time to Initiation of Cytotoxic Chemotherapy
Hide Description Time to initiation of cytotoxic chemotherapy was defined as the time from randomization to initiation of cytotoxic chemotherapy. It included only therapies for prostate cancer. When multiple cytotoxic chemotherapies were initiated, the first chemotherapy was used to determine the time to event. Participants who did not start cytotoxic chemotherapy at the time of analysis data cutoff were censored at the date of their last assessment indicating no evidence of cytotoxic chemotherapy usage.
Time Frame From randomization up to data cutoff date of 20 Sept 2015; median follow-up time is 7.39 months for enzalutamide and 4.93 months for placebo
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent-to-Treat (ITT) population consisted of all randomized participants in the study.
Arm/Group Title Enzalutamide Placebo
Hide Arm/Group Description:
Participants received 160 mg of enzalutamide orally once a day until Prostate-Specific Antigen (PSA) progression and radiographic disease progression were centrally confirmed and 1 of the following 2 events became applicable to the participants: (1) initiation of cytotoxic chemotherapy or (2) initiation of an investigational agent for treatment of prostate cancer.
Participants received matching placebo orally once a day until PSA progression and radiographic disease progression were centrally confirmed and 1 of the following 2 events became applicable to the participants: (1) initiation of cytotoxic chemotherapy or (2) initiation of an investigational agent for treatment of prostate cancer.
Overall Number of Participants Analyzed 198 190
Median (95% Confidence Interval)
Unit of Measure: Months
NA [1] 
(NA to NA)
13.93 [1] 
(NA to NA)
[1]
Could not be estimated due to the low number of events at the time of the data cutoff date.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Enzalutamide, Placebo
Comments Participants who did not start cytotoxic chemotherapy at the time of analysis data cutoff were censored at the date of the last assessment indicating no evidence of cytotoxic chemotherapy usage. Hazard ratio calculated using unstratified Cox Proportional Hazards model with treatment as the only covariate for enzalutamide group versus placebo group.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0020
Comments P-value is based on an unstratified log-rank test.
Method Unstratified log-rank test
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.28
Confidence Interval 95%
0.12 to 0.66
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Number of Participants With Confirmed Best PSA Response (≥50% Decrease From Baseline)
Hide Description Best PSA response was defined as as ≥50% reductions in PSA level from baseline to the lowest post-baseline PSA result as determined by the central laboratory, with a consecutive assessment conducted at least 3 weeks later to confirm the PSA response. Only participants who had both baseline and post-baseline assessments were included in the analysis.
Time Frame Baseline up to data cut off date of 20 Sept 2015; median treatment duration is 6.60 months for enzalutamide and 3.70 months for placebo
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent-to-Treat (ITT) population consisted of all randomized participants in the study.
Arm/Group Title Enzalutamide Placebo
Hide Arm/Group Description:
Participants received 160 mg of enzalutamide orally once a day until Prostate-Specific Antigen (PSA) progression and radiographic disease progression were centrally confirmed and 1 of the following 2 events became applicable to the participants: (1) initiation of cytotoxic chemotherapy or (2) initiation of an investigational agent for treatment of prostate cancer.
Participants received matching placebo orally once a day until PSA progression and radiographic disease progression were centrally confirmed and 1 of the following 2 events became applicable to the participants: (1) initiation of cytotoxic chemotherapy or (2) initiation of an investigational agent for treatment of prostate cancer.
Overall Number of Participants Analyzed 182 148
Measure Type: Number
Unit of Measure: Participants
120 15
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Enzalutamide, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments P-value is based on unstratified Cochran-Mantel-Haenszel mean score test.
Method Unstratified Cochran-Mantel-Haenszel %
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference of response rate
Estimated Value 55.8
Confidence Interval (2-Sided) 95%
47.4 to 64.2
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Best Overall Soft Tissue Response
Hide Description Participants with measurable soft tissue disease at screening visit (i.e., at least one target lesion per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1) who have an objective response (complete response (CR) or partial response (PR)) during the study were included in the best overall soft tissue response assessment. The best overall soft tissue response was based on the investigator assessment using RECIST 1.1.
Time Frame From randomization up to data cut off date of 20 Sept 2015; median treatment duration is 6.60 months for enzalutamide and 3.70 months for placebo
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent-to-Treat (ITT) population consisted of all randomized participants in the study.
Arm/Group Title Enzalutamide Placebo
Hide Arm/Group Description:
Participants received 160 mg of enzalutamide orally once a day until Prostate-Specific Antigen (PSA) progression and radiographic disease progression were centrally confirmed and 1 of the following 2 events became applicable to the participants: (1) initiation of cytotoxic chemotherapy or (2) initiation of an investigational agent for treatment of prostate cancer.disease progression were centrally confirmed.
Participants received matching placebo orally once a day until PSA progression and radiographic disease progression were centrally confirmed and 1 of the following 2 events became applicable to the participants: (1) initiation of cytotoxic chemotherapy or (2) initiation of an investigational agent for treatment of prostate cancer.
Overall Number of Participants Analyzed 65 60
Measure Type: Number
Unit of Measure: Participants
18 1
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Enzalutamide, Placebo
Comments When deriving the response category, it was based on the target, non-target and new lesions without confirming CR, PR, and Progressive disease (PD). Participants with no post baseline assessment were included in the category of Nonevaluable (NE). The best overall soft tissue objective response was defined as PR or CR based on the investigator assessments of target, non-target and new lesions while on the study treatment.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments P-value is based on unstratified Cochran-Mantel-Haenszel mean score test.
Method Unstratified Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in objective response rate
Estimated Value 26.0
Confidence Interval (2-Sided) 95%
14.7 to 37.4
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Time to Maximum Concentration (Tmax) of Enzalutamide, M1,M2 and Enzalutamide Plus M2
Hide Description [Not Specified]
Time Frame From randomization up to data cutoff date of 20 Jan 2016; Single Dosing Day 1 and Multiple Dosing Day 85
Hide Outcome Measure Data
Hide Analysis Population Description
The Pharmacokinetic Analysis Set (PKAS) population consisted of all participants who received at least 1 dose of study drug and who provided blood samples for drug concentrations at at least 1 time point.
Arm/Group Title Enzalutamide M1- Carboxylic Acid Metabolite M2- N-Desmethyl Enzalutamide Enzalutamide Plus M2
Hide Arm/Group Description:
Participants received 160 mg of enzalutamide orally once a day until Prostate-Specific Antigen (PSA) progression and radiographic disease progression were centrally confirmed and 1 of the following 2 events became applicable to the participants: (1) initiation of cytotoxic chemotherapy or (2) initiation of an investigational agent for treatment of prostate cancer.
Inactive metabolite
N-desmethyl enzalutamide (active metabolite)
Active metabolite
Overall Number of Participants Analyzed 12 12 12 12
Median (Full Range)
Unit of Measure: (h)
Day 1 Number Analyzed 12 participants 12 participants 12 participants 12 participants
0.975
(0.500 to 6.05)
24.0
(0.550 to 24.9)
24.0
(0.550 to 24.9)
0.975
(0.500 to 24.0)
Day 85 Number Analyzed 11 participants 11 participants 11 participants 11 participants
1.00
(0 to 2.00)
1.02
(0.217 to 24.1)
0
(0 to 23.8)
0.250
(0 to 23.8)
9.Secondary Outcome
Title Maximum Observed Plasma Concentration During the First 24 Hours After Dosing (Cmax) Enzalutamide, M1,M2 and Enzalutamide Plus M2
Hide Description [Not Specified]
Time Frame From randomization up to data cutoff date of 20 Jan 2016; Single Dosing Day 1 and Multiple Dosing Day 85
Hide Outcome Measure Data
Hide Analysis Population Description
The Pharmacokinetic Analysis Set (PKAS) population consisted of all participants who received at least 1 dose of study drug and who provided blood samples for drug concentrations at at least 1 time point.
Arm/Group Title Enzalutamide M1- Carboxylic Acid Metabolite M2- N-Desmethyl Enzalutamide Enzalutamide Plus M2
Hide Arm/Group Description:
Participants received 160 mg of enzalutamide orally once a day until Prostate-Specific Antigen (PSA) progression and radiographic disease progression were centrally confirmed and 1 of the following 2 events became applicable to the participants: (1) initiation of cytotoxic chemotherapy or (2) initiation of an investigational agent for treatment of prostate cancer.
Inactive metabolite
N-desmethyl enzalutamide (active metabolite)
[Not Specified]
Overall Number of Participants Analyzed 12 12 12 12
Mean (Standard Deviation)
Unit of Measure: μg/mL
Day 1 Number Analyzed 12 participants 12 participants 12 participants 12 participants
3.92  (1.37) 0.112  (0.0794) 0.175  (0.0921) 3.94  (1.34)
Day 85 Number Analyzed 11 participants 11 participants 11 participants 11 participants
20.0  (3.22) 14.0  (23.5) 15.2  (3.44) 34.2  (4.98)
10.Secondary Outcome
Title AUC From the Time of Dosing to 24 h After Dosing (AUC24h) Enzalutamide, M1,M2 and Enzalutamide Plus M2
Hide Description [Not Specified]
Time Frame From randomization up to data cutoff date of 20 Jan 2016; Single Dosing Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
The Pharmacokinetic Analysis Set (PKAS) population consisted of all participants who received at least 1 dose of study drug and who provided blood samples for drug concentrations at at least 1 time point. Number of participants analyzed is the number of participants with available data at this time point.
Arm/Group Title Enzalutamide M1- Carboxylic Acid Metabolite M2- N-Desmethyl Enzalutamide Enzalutamide Plus M2
Hide Arm/Group Description:
Participants received 160 mg of enzalutamide orally once a day until Prostate-Specific Antigen (PSA) progression and radiographic disease progression were centrally confirmed.
Inactive metabolite
N-desmethyl enzalutamide (active metabolite)
Active metabolite
Overall Number of Participants Analyzed 12 12 12 12
Mean (Standard Deviation)
Unit of Measure: μg·h/mL
43.1  (9.64) 1.81  (0.972) 2.17  (1.30) 45.3  (10.1)
11.Secondary Outcome
Title Concentration 24 h After Dosing (C24h) Enzalutamide, M1,M2 and Enzalutamide Plus M2
Hide Description N is the number of participants with available data at this time point.
Time Frame From randomization up to data cutoff date of 20 Jan 2016; Single Dosing Day 1 and Multiple Dosing Day 85
Hide Outcome Measure Data
Hide Analysis Population Description
The Pharmacokinetic Analysis Set (PKAS) population consisted of all participants who received at least 1 dose of study drug and who provided blood samples for drug concentrations at at least 1 time point.
Arm/Group Title Enzalutamide M1- Carboxylic Acid Metabolite M2- N-Desmethyl Enzalutamide Enzalutamide Plus M2
Hide Arm/Group Description:
Participants received 160 mg of enzalutamide orally once a day until Prostate-Specific Antigen (PSA) progression and radiographic disease progression were centrally confirmed and 1 of the following 2 events became applicable to the participants: (1) initiation of cytotoxic chemotherapy or (2) initiation of an investigational agent for treatment of prostate cancer.
Inactive metabolite
N-desmethyl enzalutamide (active metabolite)
Active metabolite
Overall Number of Participants Analyzed 12 12 12 12
Mean (Standard Deviation)
Unit of Measure: μg/mL
Day 1 Number Analyzed 12 participants 12 participants 12 participants 12 participants
1.65  (0.343) 0.111  (0.0801) 0.164  (0.0942) 1.82  (0.363)
Day 85 Number Analyzed 10 participants 10 participants 10 participants 10 participants
17.6  (3.09) 6.09  (3.07) 13.7  (2.91) 31.2  (4.00)
12.Secondary Outcome
Title Observed Plasma Concentration in Predose Samples Obtained During Multiple-dose Administration of Minimum Concentration (Plasma Concentration at Pre Dose) (Cmin) Enzalutamide, M1,M2 and Enzalutamide Plus M2
Hide Description N is the number of participants with available data at this time point.
Time Frame From randomization up to data cutoff date of 20 Jan 2016; Day 2, 3, 8, 22, 29, 43, 57, 85, 86, 113, 141 and 169
Hide Outcome Measure Data
Hide Analysis Population Description
The Pharmacokinetic Analysis Set (PKAS) population consisted of all participants who received at least 1 dose of study drug and who provided blood samples for drug concentrations at least 1 time point.
Arm/Group Title Enzalutamide M1- Carboxylic Acid Metabolite M2- N-Desmethyl Enzalutamide Enzalutamide Plus M2
Hide Arm/Group Description:
Participants received 160 mg of enzalutamide orally once a day until Prostate-Specific Antigen (PSA) progression and radiographic disease progression were centrally confirmed and 1 of the following 2 events became applicable to the participants: (1) initiation of cytotoxic chemotherapy or (2) initiation of an investigational agent for treatment of prostate cancer.
Inactive metabolite.
N-desmethyl enzalutamide (active metabolite).
Active metabolite.
Overall Number of Participants Analyzed 12 12 12 12
Mean (Standard Deviation)
Unit of Measure: μg/mL
Day 2 predose Number Analyzed 12 participants 12 participants 12 participants 12 participants
1.65  (0.343) 0.111  (0.0801) 0.164  (0.0942) 1.82  (0.363)
Day 3 predose Number Analyzed 12 participants 12 participants 12 participants 12 participants
3.29  (1.16) 0.302  (0.256) 0.367  (0.188) 3.66  (1.24)
Day 8 predose Number Analyzed 12 participants 12 participants 12 participants 12 participants
9.39  (2.07) 1.21  (0.923) 1.94  (0.983) 11.3  (2.62)
Day 22 predose Number Analyzed 11 participants 11 participants 11 participants 11 participants
17.6  (2.37) 6.09  (8.26) 8.34  (2.74) 25.9  (3.25)
Day 29 predose Number Analyzed 12 participants 12 participants 12 participants 12 participants
19.6  (4.00) 8.16  (12.5) 10.9  (3.72) 30.5  (5.47)
Day 43 predose Number Analyzed 11 participants 11 participants 11 participants 11 participants
17.0  (4.13) 12.5  (22.1) 14.0  (3.99) 31.0  (5.82)
Day 57 predose Number Analyzed 11 participants 11 participants 11 participants 11 participants
17.8  (3.09) 18.4  (28.2) 14.7  (3.88) 32.5  (4.57)
Day 85 predose Number Analyzed 11 participants 11 participants 11 participants 11 participants
17.9  (3.19) 6.33  (2.95) 14.9  (3.67) 32.8  (5.10)
Day 86 predose Number Analyzed 10 participants 10 participants 10 participants 10 participants
17.6  (3.09) 6.09  (3.07) 13.7  (2.91) 31.2  (4.00)
Day 113 predose Number Analyzed 7 participants 7 participants 7 participants 7 participants
17.5  (4.14) 17.5  (33.1) 15.0  (3.21) 32.5  (3.72)
Day 141 predose Number Analyzed 6 participants 6 participants 6 participants 6 participants
17.3  (3.73) 5.52  (2.10) 14.3  (3.90) 31.6  (4.70)
Day 169 predose Number Analyzed 4 participants 4 participants 4 participants 4 participants
17.2  (5.55) 5.09  (2.27) 14.0  (4.80) 31.2  (5.02)
13.Secondary Outcome
Title Apparent Total Systemic Clearance After Multiple Dosing (CL/F) Enzalutamide, M1,M2 and Enzalutamide Plus M2 (For Unchanged Enzalutamide Only)
Hide Description [Not Specified]
Time Frame From randomization up to data cutoff date of 20 Jan 2016; Multiple Dosing Day 85
Hide Outcome Measure Data
Hide Analysis Population Description
The Pharmacokinetic Analysis Set (PKAS) population consisted of all participants who received at least 1 dose of study drug and who provided blood samples for drug concentrations at at least 1 time point.
Arm/Group Title Enzalutamide M1- Carboxylic Acid Metabolite M2- N-Desmethyl Enzalutamide Enzalutamide Plus M2
Hide Arm/Group Description:
Participants received 160 mg of enzalutamide orally once a day until Prostate-Specific Antigen (PSA) progression and radiographic disease progression were centrally confirmed and 1 of the following 2 events became applicable to the participants: (1) initiation of cytotoxic chemotherapy or (2) initiation of an investigational agent for treatment of prostate cancer.
Inactive metabolite.
Active metabolite.
Active metabolite.
Overall Number of Participants Analyzed 10 10 10 10
Mean (Standard Error)
Unit of Measure: L/h
0.387  (0.0774) NA [1]   (NA) NA [1]   (NA) NA [1]   (NA)
[1]
Metabolite dose was unknown.
14.Secondary Outcome
Title Peak-Trough Ratio (PTR) Enzalutamide, M1,M2 and Enzalutamide Plus M2
Hide Description [Not Specified]
Time Frame From randomization up to data cutoff date of 20 Jan 2016; Multiple Dosing Day 85
Hide Outcome Measure Data
Hide Analysis Population Description
The Pharmacokinetic Analysis Set (PKAS) population consisted of all participants who received at least 1 dose of study drug and who provided blood samples for drug concentrations at at least 1 time point.
Arm/Group Title Enzalutamide M1- Carboxylic Acid Metabolite M2- N-Desmethyl Enzalutamide Enzalutamide Plus M2
Hide Arm/Group Description:
Participants received 160 mg of enzalutamide orally once a day until Prostate-Specific Antigen (PSA) progression and radiographic disease progression were centrally confirmed and 1 of the following 2 events became applicable to the participants: (1) initiation of cytotoxic chemotherapy or (2) initiation of an investigational agent for treatment of prostate cancer.
Inactive metabolite.
N-desmethyl enzalutamide (active metabolite).
Active metabolite.
Overall Number of Participants Analyzed 10 10 10 10
Mean (Standard Deviation)
Unit of Measure: Ratio
1.15  (0.110) 1.19  (0.364) 1.09  (0.0897) 1.08  (0.0581)
15.Secondary Outcome
Title AUC From the Time of Dosing to the Start of the Next Dosing Interval (AUCtau) Enzalutamide, M1,M2 and Enzalutamide Plus M2
Hide Description [Not Specified]
Time Frame From randomization up to data cutoff date of 20 Jan 2016; Multiple Dosing Day 85
Hide Outcome Measure Data
Hide Analysis Population Description
The Pharmacokinetic Analysis Set (PKAS) population consisted of all participants who received at least 1 dose of study drug and who provided blood samples for drug concentrations at at least 1 time point.
Arm/Group Title Enzalutamide M1- Carboxylic Acid Metabolite M2- N-Desmethyl Enzalutamide Enzalutamide Plus M2
Hide Arm/Group Description:
Participants received 160 mg of enzalutamide orally once a day until Prostate-Specific Antigen (PSA) progression and radiographic disease progression were centrally confirmed and 1 of the following 2 events became applicable to the participants: (1) initiation of cytotoxic chemotherapy or (2) initiation of an investigational agent for treatment of prostate cancer.
Inactive metabolite
N-desmethyl enzalutamide (active metabolite)
Active metabolite
Overall Number of Participants Analyzed 10 10 10 10
Mean (Standard Deviation)
Unit of Measure: μg·h/mL
427  (79.8) 149  (74.1) 308  (68.2) 735  (109)
16.Secondary Outcome
Title Number of Participants With Adverse Events
Hide Description The Treatment-Emergent Adverse Events are defined as AEs with a possible or probable relationship to study drug. If participant was still on study drug at the analysis data cutoff date, then the length of the treatment-emergent period was calculated through the cutoff date.
Time Frame From first dose of study drug up to data cut off date of 20 Sept 2015
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Analysis Set consisted of all randomized participants who received at least 1 dose of study drug.
Arm/Group Title Enzalutamide Placebo
Hide Arm/Group Description:
Participants received 160 mg of enzalutamide orally once a day until Prostate-Specific Antigen (PSA) progression and radiographic disease progression were centrally confirmed and 1 of the following 2 events became applicable to the participants: (1) initiation of cytotoxic chemotherapy or (2) initiation of an investigational agent for treatment of prostate cancer.
Participants received matching placebo orally once a day until PSA progression and radiographic disease progression were centrally confirmed and 1 of the following 2 events became applicable to the participants: (1) initiation of cytotoxic chemotherapy or (2) initiation of an investigational agent for treatment of prostate cancer.
Overall Number of Participants Analyzed 198 190
Measure Type: Number
Unit of Measure: Participants
Adverse Events (AEs) 167 153
AEs of Special Interest 85 54
AEs Leading to Study Drug Discontinuation 26 34
Drug-related AEs 85 54
Drug-related AEs Leading to Drug Discontinuation 6 7
Grade 3 or Higher AEs 49 56
Serious Adverse Events (SAEs) 34 47
Drug-related SAEs 7 6
SAEs Leading to Study Drug Discontinuation 10 17
SAEs Leading to Death 7 6
Drug-related SAEs Leading to Death 0 0
Time Frame From first dose of study drug up to data cut off 20 Sept 2015.
Adverse Event Reporting Description Median treatment emergent period length (months) for Enzalutamide 7.10 and Placebo 4.35.
 
Arm/Group Title Enzalutamide Placebo
Hide Arm/Group Description Participants received 160 mg of enzalutamide orally once a day until Prostate-Specific Antigen (PSA) progression and radiographic disease progression were centrally confirmed and 1 of the following 2 events became applicable to the participants: (1) initiation of cytotoxic chemotherapy or (2) initiation of an investigational agent for treatment of prostate cancer. Participants received matching placebo orally once a day until PSA progression and radiographic disease progression were centrally confirmed and 1 of the following 2 events became applicable to the participants: (1) initiation of cytotoxic chemotherapy or (2) initiation of an investigational agent for treatment of prostate cancer.
All-Cause Mortality
Enzalutamide Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Enzalutamide Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   34/198 (17.17%)   47/190 (24.74%) 
Blood and lymphatic system disorders     
Anaemia  1  1/198 (0.51%)  4/190 (2.11%) 
Haemorrhagic anaemia  1  1/198 (0.51%)  0/190 (0.00%) 
Thrombocytopenia  1  0/198 (0.00%)  1/190 (0.53%) 
Cardiac disorders     
Cardiac failure  1  2/198 (1.01%)  0/190 (0.00%) 
Acute myocardial infarction  1  1/198 (0.51%)  0/190 (0.00%) 
Angina pectoris  1  0/198 (0.00%)  1/190 (0.53%) 
Angina unstable  1  0/198 (0.00%)  1/190 (0.53%) 
Cardiopulmonary failure  1  1/198 (0.51%)  0/190 (0.00%) 
Supraventricular tachycardia  1  1/198 (0.51%)  0/190 (0.00%) 
Eye disorders     
Cataract  1  1/198 (0.51%)  0/190 (0.00%) 
Gastrointestinal disorders     
Abdominal pain  1  1/198 (0.51%)  1/190 (0.53%) 
Gastric ulcer haemorrhage  1  1/198 (0.51%)  1/190 (0.53%) 
Gastrointestinal haemorrhage  1  2/198 (1.01%)  0/190 (0.00%) 
Intestinal obstruction  1  2/198 (1.01%)  0/190 (0.00%) 
Upper gastrointestinal haemorrhage  1  2/198 (1.01%)  0/190 (0.00%) 
Constipation  1  0/198 (0.00%)  1/190 (0.53%) 
Duodenal ulcer  1  1/198 (0.51%)  0/190 (0.00%) 
Dyspepsia  1  0/198 (0.00%)  1/190 (0.53%) 
Gastric mucosal lesion  1  1/198 (0.51%)  0/190 (0.00%) 
Gastritis erosive  1  0/198 (0.00%)  1/190 (0.53%) 
Inguinal hernia  1  1/198 (0.51%)  0/190 (0.00%) 
Small intestinal obstruction  1  1/198 (0.51%)  0/190 (0.00%) 
General disorders     
Asthenia  1  2/198 (1.01%)  2/190 (1.05%) 
Death  1  0/198 (0.00%)  2/190 (1.05%) 
Pyrexia  1  1/198 (0.51%)  1/190 (0.53%) 
Malaise  1  0/198 (0.00%)  1/190 (0.53%) 
Multi-organ failure  1  0/198 (0.00%)  1/190 (0.53%) 
Oedema peripheral  1  0/198 (0.00%)  1/190 (0.53%) 
Hepatobiliary disorders     
Cholecystitis acute  1  0/198 (0.00%)  1/190 (0.53%) 
Cholecystitis chronic  1  0/198 (0.00%)  1/190 (0.53%) 
Infections and infestations     
Lung infection  1  4/198 (2.02%)  0/190 (0.00%) 
Pneumonia  1  1/198 (0.51%)  0/190 (0.00%) 
Septic shock  1  1/198 (0.51%)  1/190 (0.53%) 
Upper respiratory tract infection  1  0/198 (0.00%)  2/190 (1.05%) 
Urinary tract infection  1  1/198 (0.51%)  1/190 (0.53%) 
Arthritis infective  1  1/198 (0.51%)  0/190 (0.00%) 
Bronchitis  1  0/198 (0.00%)  1/190 (0.53%) 
Cellulitis  1  1/198 (0.51%)  0/190 (0.00%) 
Chronic sinusitis  1  0/198 (0.00%)  1/190 (0.53%) 
Influenza  1  1/198 (0.51%)  0/190 (0.00%) 
Subcutaneous abscess  1  1/198 (0.51%)  0/190 (0.00%) 
Urosepsis  1  1/198 (0.51%)  0/190 (0.00%) 
Injury, poisoning and procedural complications     
Femur fracture  1  0/198 (0.00%)  1/190 (0.53%) 
Spinal compression fracture  1  1/198 (0.51%)  0/190 (0.00%) 
Investigations     
Prostatic specific antigen increased  1  1/198 (0.51%)  1/190 (0.53%) 
Neutrophil count decreased  1  1/198 (0.51%)  0/190 (0.00%) 
Metabolism and nutrition disorders     
Decreased appetite  1  2/198 (1.01%)  1/190 (0.53%) 
Cachexia  1  1/198 (0.51%)  0/190 (0.00%) 
Musculoskeletal and connective tissue disorders     
Back pain  1  1/198 (0.51%)  2/190 (1.05%) 
Bone pain  1  1/198 (0.51%)  2/190 (1.05%) 
Pain in extremity  1  1/198 (0.51%)  1/190 (0.53%) 
Arthritis  1  0/198 (0.00%)  1/190 (0.53%) 
Flank pain  1  0/198 (0.00%)  1/190 (0.53%) 
Lumbar spinal stenosis  1  0/198 (0.00%)  1/190 (0.53%) 
Muscular weakness  1  1/198 (0.51%)  0/190 (0.00%) 
Osteonecrosis of jaw  1  1/198 (0.51%)  0/190 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
B-cell lymphoma  1  1/198 (0.51%)  0/190 (0.00%) 
Gastric cancer  1  0/198 (0.00%)  1/190 (0.53%) 
Metastases to central nervous system  1  0/198 (0.00%)  1/190 (0.53%) 
Metastases to rectum  1  0/198 (0.00%)  1/190 (0.53%) 
Renal cell carcinoma  1  0/198 (0.00%)  1/190 (0.53%) 
Small cell lung cancer  1  0/198 (0.00%)  1/190 (0.53%) 
Tumour associated fever  1  0/198 (0.00%)  1/190 (0.53%) 
Nervous system disorders     
Cerebral infarction  1  2/198 (1.01%)  1/190 (0.53%) 
Dizziness  1  2/198 (1.01%)  0/190 (0.00%) 
Cerebrovascular accident  1  1/198 (0.51%)  0/190 (0.00%) 
Loss of consciousness  1  1/198 (0.51%)  0/190 (0.00%) 
Syncope  1  0/198 (0.00%)  1/190 (0.53%) 
Psychiatric disorders     
Mental disorder due to a general medical condition  1  0/198 (0.00%)  1/190 (0.53%) 
Renal and urinary disorders     
Haematuria  1  4/198 (2.02%)  5/190 (2.63%) 
Urinary retention  1  3/198 (1.52%)  1/190 (0.53%) 
Dysuria  1  0/198 (0.00%)  2/190 (1.05%) 
Hydronephrosis  1  1/198 (0.51%)  1/190 (0.53%) 
Renal failure acute  1  1/198 (0.51%)  1/190 (0.53%) 
Azotaemia  1  0/198 (0.00%)  1/190 (0.53%) 
Calculus bladder  1  1/198 (0.51%)  0/190 (0.00%) 
Ureteric rupture  1  0/198 (0.00%)  1/190 (0.53%) 
Urinary tract obstruction  1  0/198 (0.00%)  1/190 (0.53%) 
Reproductive system and breast disorders     
Benign prostatic hyperplasia  1  0/198 (0.00%)  1/190 (0.53%) 
Prostatic haemorrhage  1  1/198 (0.51%)  0/190 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Pulmonary embolism  1  1/198 (0.51%)  1/190 (0.53%) 
Respiratory failure  1  0/198 (0.00%)  2/190 (1.05%) 
Dyspnoea  1  0/198 (0.00%)  1/190 (0.53%) 
Pleural effusion  1  0/198 (0.00%)  1/190 (0.53%) 
Pulmonary oedema  1  0/198 (0.00%)  1/190 (0.53%) 
Surgical and medical procedures     
Chemotherapy  1  0/198 (0.00%)  4/190 (2.11%) 
Medical device change  1  1/198 (0.51%)  0/190 (0.00%) 
Nephrostomy tube removal  1  1/198 (0.51%)  0/190 (0.00%) 
Radiotherapy  1  0/198 (0.00%)  1/190 (0.53%) 
Ureteral stent removal  1  1/198 (0.51%)  0/190 (0.00%) 
Vascular disorders     
Hypertension  1  1/198 (0.51%)  0/190 (0.00%) 
Hypotension  1  0/198 (0.00%)  1/190 (0.53%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA v 16.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Enzalutamide Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   167/198 (84.34%)   153/190 (80.53%) 
Blood and lymphatic system disorders     
Anaemia  1  12/198 (6.06%)  17/190 (8.95%) 
Gastrointestinal disorders     
Constipation  1  17/198 (8.59%)  13/190 (6.84%) 
Nausea  1  14/198 (7.07%)  9/190 (4.74%) 
General disorders     
Fatigue  1  25/198 (12.63%)  12/190 (6.32%) 
Pyrexia  1  10/198 (5.05%)  13/190 (6.84%) 
Asthenia  1  10/198 (5.05%)  7/190 (3.68%) 
Infections and infestations     
Nasopharyngitis  1  13/198 (6.57%)  6/190 (3.16%) 
Investigations     
Weight decreased  1  10/198 (5.05%)  10/190 (5.26%) 
Metabolism and nutrition disorders     
Decreased appetite  1  24/198 (12.12%)  17/190 (8.95%) 
Musculoskeletal and connective tissue disorders     
Back pain  1  19/198 (9.60%)  18/190 (9.47%) 
Bone pain  1  12/198 (6.06%)  25/190 (13.16%) 
Pain in extremity  1  14/198 (7.07%)  17/190 (8.95%) 
Arthralgia  1  15/198 (7.58%)  13/190 (6.84%) 
Musculoskeletal pain  1  10/198 (5.05%)  5/190 (2.63%) 
Nervous system disorders     
Dizziness  1  17/198 (8.59%)  7/190 (3.68%) 
Psychiatric disorders     
Insomnia  1  10/198 (5.05%)  5/190 (2.63%) 
Renal and urinary disorders     
Haematuria  1  7/198 (3.54%)  13/190 (6.84%) 
Vascular disorders     
Hypertension  1  16/198 (8.08%)  2/190 (1.05%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA v 16.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Institution and/or Principal Investigator may publish trial data generated at their specific study site after Sponsor publication of the multi-center data or 18 months after study completion date at all sites, whichever is first. Sponsor must receive a site’s manuscript at least 45 days prior to publication for review and comment. If requested Sponsor may delay the publication for up to 60 days to seek patent protection.
Results Point of Contact
Name/Title: Clinical Trial Disclosure
Organization: Astellas Pharma Inc
Responsible Party: Astellas Pharma Inc
ClinicalTrials.gov Identifier: NCT02294461     History of Changes
Other Study ID Numbers: 9785-CL-0232
First Submitted: November 13, 2014
First Posted: November 19, 2014
Results First Submitted: December 12, 2016
Results First Posted: April 12, 2017
Last Update Posted: December 11, 2018