A Study of Enzalutamide Versus Bicalutamide in Castrate Men With Metastatic Prostate Cancer
Sponsor
Astellas Pharma Inc (Industry)
Overall Status
Completed
CT.gov ID
NCT01288911
Collaborator
Medivation LLC, a wholly owned subsidiary of Pfizer Inc. (Industry)
375
88
2
79.6
4.3
0.1
Study Details
Study Description
Brief Summary
The purpose of this study was to determine the efficacy and safety of oral enzalutamide compared to bicalutamide in castrate men with metastatic prostate cancer who have progressed while on Luteinizing Hormone Receptor Hormone (LHRH) agonist/antagonist or after receiving a bilateral orchiectomy.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Detailed Description
An open-label period was added to the main protocol. Following unblinding at the end of the double-blind period and demonstration of a statistically significant advantage of enzalutamide over bicalutamide as assessed by the primary endpoint, all ongoing enzalutamide treated participants and ongoing or previous bicalutamide treated participants that met entry criteria were offered open-label enzalutamide at the discretion of the participant and study investigators.
Study Design
Study Type:
Interventional
Actual Enrollment
:
375 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Randomized, Double-Blind, Phase II, Efficacy and Safety Study of MDV3100 Versus Bicalutamide in Castrate Men With Metastatic Prostate Cancer
Actual Study Start Date
:
Mar 22, 2011
Actual Primary Completion Date
:
Oct 19, 2014
Actual Study Completion Date
:
Nov 8, 2017
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Enzalutamide Participants received enzalutamide 160 mg orally once daily until confirmed radiographic disease progression, skeletal-related event or the initiation of a new antineoplastic therapy. |
Drug: enzalutamide
capsules
Other Names:
|
| Active Comparator: Bicalutamide Participants received bicalutamide 50 mg orally once daily until confirmed radiographic disease progression, skeletal-related event or the initiation of a new antineoplastic therapy. |
Drug: bicalutamide
tablets
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Progression Free Survival (PFS) Based on Independent Central Review (ICR) Assessment [From randomization until the data cut-off date of 19 October 2014, median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm.]
PFS is the time from randomization to the date of the first progression event detected. A progression event was defined as objective evidence of radiographic disease progression based on the assessments by the ICR, skeletal-related event, initiation of new antineoplastic therapy or death by any cause, whichever occurred first. Radiographic disease progression was defined as either a progression in soft tissue on computed tomography (CT)/magnetic resonance imaging (MRI) scan according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, and/or a progression in bone lesions on bone scan (≥ 2 new bone lesions) confirmed by the next bone scan. A skeletal-related event was any radiation therapy or surgery to bone, pathologic bone fracture, spinal cord compression or change in antineoplastic therapy to treat bone pain. The initiation of new antineoplastic therapy included any new therapy for the treatment of disease progression after the study drug administration started.
Secondary Outcome Measures
- PFS Based on Investigator Assessment [From randomization until the data cut-off date of 19 October 2014, median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm.]
PFS was calculated as the time from randomization to the date of the first progression event detected. A progression event was defined as objective evidence of radiographic disease progression based on the assessments by investigators, skeletal-related event, initiation of new antineoplastic therapy or death by any cause, whichever occurred first. Radiographic disease progression was defined as either a progression in soft tissue on CT/MRI scan according to RECIST 1.1, and/or a progression in bone lesions on bone scan (≥ 2 new bone lesions) confirmed by the next bone scan. A skeletal-related event was defined as radiation therapy or surgery to bone, pathologic bone fracture, spinal cord compression or change in antineoplastic therapy to treat bone pain. The initiation of new antineoplastic therapy included any new therapy for the treatment of disease progression after the study drug administration started.
- Prostate-specific Antigen (PSA) Response by Week 13 [Baseline to Week 13]
The PSA response by Week 13 was defined as the percentage change from Baseline to the smallest PSA value after Baseline (i.e., a decrease of 100% represents the largest possible decrease to a value below the lower limit of quantification) and on or before day 99 (i.e., upper boundary of the Week 13 visit window). For participants with no decrease in PSA post-baseline by Week 13, the PSA response by Week 13 was the smallest increase in PSA up to day 99. For participants with no post-baseline PSA values up to day 99, the PSA response by Week 13 was set to missing. PSA was analyzed at a central laboratory.
- Best PSA Response [Baseline to the data cutoff date of 19 October 2014, median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm.]
The best PSA response was defined as the percentage change from Baseline to the smallest PSA value after Baseline including PSA results from samples taken after the study drug was stopped. For participants with no decrease in PSA post-baseline, the best PSA response was the smallest increase in PSA. For participants with no post-baseline PSA values, the PSA response was set to missing. PSA was analyzed at a central laboratory.
- Time to PSA Progression [From randomization until the data cutoff date of 19 October 2014, median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm.]
Time to PSA progression was calculated as the time interval from the date of randomization to the date of first observation of PSA progression. PSA progression was defined as a ≥ 25% increase and an absolute increase of ≥ 2 ng/mL above the nadir (or above the baseline value for participants who did not have a decline in PSA post-baseline values), and confirmed by a second consecutive PSA assessment at least 3 weeks later. For participants with no documented PSA progression, the time to PSA progression was censored on the date the last PSA sample was taken.
- Time to PSA ≤ 4 ng/mL [From randomization until the data cutoff date of 19 October 2014, median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm.]
Time to PSA ≤ 4 ng/mL was defined as the time interval from the date of randomization to the first date a decline in PSA to a result of 4 ng/mL or below was recorded. In participants without PSA results ≤ 4 ng/mL, the time to PSA ≤ 4 ng/mL was censored on the date of the last PSA sample taken. Participants with a PSA result ≤ 4 ng/mL at Baseline, participants with no Baseline PSA and participants with no post-baseline PSA results were censored on the date of randomization
- Time to ≥ 30% PSA Decline From Baseline [From randomization until the data cutoff date of 19 October 2014, median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm.]
The time to ≥ 30% PSA decline from Baseline was defined as the time interval from the date of randomization to the first date a PSA decline from Baseline of at least 30% was recorded. In participants without ≥ 30% PSA decline from Baseline, the time to ≥ 30% PSA decline from Baseline was censored on the date of the last PSA sample taken. Participants who had no Baseline PSA and participants with no post-baseline PSA results were censored on the date of randomization.
- Time to ≥ 50% PSA Decline From Baseline [From randomization until the data cutoff date of 19 October 2014, median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm.]
The time to ≥ 50% PSA decline from Baseline was defined as the time interval from the date of randomization to the first date a PSA decline from Baseline of at least 50% was recorded. In participants without ≥ 50% PSA decline from Baseline, the time to ≥ 50% PSA decline from Baseline was censored on the date of the last PSA sample taken. Participants who had no Baseline PSA and participants with no post-baseline PSA results were censored on the date of randomization.
- Time to ≥ 90% PSA Decline From Baseline [From randomization until the data cutoff date of 19 October 2014, median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm.]
The time to ≥ 90% PSA decline from Baseline was defined as the time interval from the date of randomization to the first date a PSA decline from Baseline of at least 90% was recorded. In participants without ≥ 90% PSA decline from Baseline, the time to ≥ 90% PSA decline from Baseline was censored on the date of the last PSA sample taken. Participants who had no Baseline PSA and participants with no post-baseline PSA results were censored on the date of randomization.
- Radiographic PFS Based on ICR Assessment [From randomization until the data cutoff date of 19 October 2014, median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm.]
Radiographic PFS was calculated as the time interval from the date of randomization to the first date of radiographic disease progression. Radiographic disease progression was defined as either a progression in soft tissue on CT/MRI scan according to RECIST 1.1, and/or a progression in bone lesions (a minimum of 2 new bone lesions as compared to previous scan) on bone scan and confirmed by the next bone scan.
- Percentage of Participants With an Objective Response [From randomization until the data cutoff date of 19 October 2014, median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm.]
Response assessments were reported by ICR for target lesions in soft tissues and non-target lesions in soft tissues based on CT and/or MRI according to RECIST version 1.1. Objective response was defined as the number of participants achieving either a complete response (CR) or a partial response (PR) based on participant's best overall response assessed at the end of the treatment.
- Percentage of Participants With Adverse Events [From initiation of study drug up to 30 days after last dose of study drug or the 30-day safety follow-up visit, whichever was last (Median duration of treatment was 11.6 months in enzalutamide arm and 5.8 in bicalutamide arm, 12.6 in the total arm).]
A serious adverse event was defined as any untoward medical occurrence that at any dose: Resulted in death Was life threatening Resulted in persistent or significant disability/incapacity Resulted in congenital anomaly or birth defect Required inpatient hospitalization or led to prolongation of hospitalization Other medically important events. Treatment-related indicates adverse events assessed by the Investigator as probably or possibly related to study treatment. Treatment emergent adverse events (TEAEs) were defined as adverse events (AEs) that started or worsened after starting administration of study drug through end of the study (i.e., the treatment-emergent period).
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
Male
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Histologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features
-
Ongoing androgen deprivation therapy with a Luteinizing Hormone Receptor Hormone (LHRH) agonist or antagonist at a stable dose and schedule within 4 weeks of randomization or bilateral orchiectomy (i.e., surgical or medical castration)
-
Metastatic disease documented by one of the following:
-
At least two bone lesions on bone scan, or
-
Soft tissue disease documented by computed tomography (CT)/ magnetic resonance imaging (MRI), or
-
Unequivocal pelvic adenopathy short axis > 2.0 cm in diameter by CT/MRI
-
Progressive disease at study entry defined as one or more of the following three criteria occurring in the setting of castrate levels of testosterone:
-
Prostate Specific Antigen (PSA) progression defined by a minimum of three rising PSA levels with an interval of ≥ 1 week between each determination. The PSA value should be ≥ 2 µg/L (2 ng/mL);
-
Soft tissue disease progression defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1;
-
Bone disease progression defined by two or more new lesions on bone scan
-
Asymptomatic or mildly symptomatic from prostate cancer (i.e. the score on the Brief Pain Inventory-Short Form (BPI-SF) Question #3 must be < 4); no use of opiate analgesics for prostate cancer-related pain currently or anytime within 4 weeks prior to randomization
-
Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, including subjects with decreased performance status not attributed to progressive and symptomatic prostate cancer
-
Estimated life expectancy of ≥ 12 months
-
Able to swallow the study drug and comply with study requirements
-
A male subject and his female spouse/partner who is of childbearing potential must use two acceptable methods of birth control (one of which must include a condom as a barrier method of contraception) starting at Screening and continuing throughout the study period, and for 3 months after final study drug administration. Two acceptable forms of birth control include:
-
Condom (barrier method of contraception), AND
-
In addition to a condom, one of the following acceptable forms of contraception is required:
-
Established use of oral, injected or implanted hormonal methods of contraception.
-
Placement of an intrauterine device (IUD) or intrauterine system (IUS).
-
Barrier methods of contraception: Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository.
-
Tubal ligation for at least 6 months prior to Screening
-
Vasectomy or other surgical castration at least 6 months prior to Screening
Exclusion Criteria:
-
Prior cytotoxic chemotherapy for prostate cancer
-
Severe concurrent disease, infection, or comorbidity that would make the subject inappropriate for enrollment
-
Known or suspected brain and/or skull metastasis or active epidural disease
-
History of another malignancy within the previous 5 years other than curatively treated non-melanomatous skin cancer
-
Current or prior treatment with estrogens and/or drugs with anti-androgenic properties such as spironolactone > 50 mg/day, or progestational agents for the treatment of prostate cancer within 6 months prior to randomization
-
Current or prior use of ketoconazole for the treatment of prostate cancer
-
Use of antiandrogens within 6 weeks prior to randomization
-
Documented prior disease progression while receiving antiandrogens. Disease progression defined as PSA progression, radiographic progression and/or clinical deterioration.
-
Current or prior treatment with 5-α reductase inhibitors or anabolic steroids within 6 months prior to randomization
-
Prior use of systemic glucocorticoids (the equivalent of 10 mg of prednisone) within 3 months prior to randomization or expectation of their use during the study
-
Radiation therapy to bone lesions or prostatic bed within 4 weeks prior to randomization
-
Major surgery within 2 months prior to randomization
-
History of seizure including febrile seizure or any condition that may predispose to seizure (e.g., prior stroke, brain arteriovenous malformation, head trauma with loss of consciousness requiring hospitalization). Also, current or prior treatment with anti-epileptic medications for the treatment of seizures or history of loss of consciousness or transient ischemic attack within 12 months prior to randomization
-
Clinically significant cardiovascular disease including myocardial infarction within past six months or uncontrolled angina within past three months
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Site US1934 | Homewood | Alabama | United States | 35209 |
| 2 | Site US1527 | Anchorage | Alaska | United States | 99503 |
| 3 | Site US3026 | Tucson | Arizona | United States | 85715 |
| 4 | Site US2977 | Highland | California | United States | 92346 |
| 5 | Site US3630 | San Diego | California | United States | 92123 |
| 6 | Site US2935 | Denver | Colorado | United States | 80211 |
| 7 | Site US2945 | Middlebury | Connecticut | United States | 06762 |
| 8 | Site US2014 | Melrose Park | Illinois | United States | 60160 |
| 9 | Site US2067 | Springfield | Illinois | United States | 62703 |
| 10 | Site US2027 | Jeffersonville | Indiana | United States | 47130 |
| 11 | Site US1838 | West Des Moines | Iowa | United States | 50266 |
| 12 | Site US62 | Kansas City | Kansas | United States | 66160-7233 |
| 13 | Site US2976 | Baltimore | Maryland | United States | 21201 |
| 14 | Site US3182 | Bethesda | Maryland | United States | 20889-5600 |
| 15 | Site US2975 | Ann Arbor | Michigan | United States | 48109 |
| 16 | Site US892 | Grand Rapids | Michigan | United States | 49546 |
| 17 | Site US20 | Minneapolis | Minnesota | United States | 55455 |
| 18 | Site US3078 | Billings | Montana | United States | 59101 |
| 19 | Site US2968 | Lawrenceville | New Jersey | United States | 08648 |
| 20 | Site US3025 | Poughkeepsie | New York | United States | 12601 |
| 21 | Site US1675 | Rochester | New York | United States | 14642 |
| 22 | Site US2934 | Staten Island | New York | United States | 10304 |
| 23 | Site US81 | Chapel Hill | North Carolina | United States | 27599 |
| 24 | Site US2104 | Greensboro | North Carolina | United States | 27403 |
| 25 | Site US44 | Cincinnati | Ohio | United States | 45267 |
| 26 | Site US2185 | Columbus | Ohio | United States | 43221 |
| 27 | Site US1598 | Bala-Cynwyd | Pennsylvania | United States | 19004 |
| 28 | Site US1680 | Lancaster | Pennsylvania | United States | 17604 |
| 29 | Site US2926 | Myrtle Beach | South Carolina | United States | 29572 |
| 30 | Site US1657 | Nashville | Tennessee | United States | 37209 |
| 31 | Site US464 | Houston | Texas | United States | 77030 |
| 32 | Site US2978 | San Antonio | Texas | United States | 78229 |
| 33 | Site US1653 | Virginia Beach | Virginia | United States | 23462 |
| 34 | Site US1580 | Burien | Washington | United States | 98166 |
| 35 | Site US1709 | Wenatchee | Washington | United States | 98801 |
| 36 | Site US51 | Milwaukee | Wisconsin | United States | 53226 |
| 37 | Site BE3015 | Brussels | Belgium | 1090 | |
| 38 | Site BE1322 | Gent | Belgium | 9000 | |
| 39 | Site BE3018 | Kortrijk | Belgium | 8500 | |
| 40 | Site BE3288 | Leuven | Belgium | 3000 | |
| 41 | Site BE3289 | Liege | Belgium | ||
| 42 | Site BE3013 | Turnhout | Belgium | 2300 | |
| 43 | Site CA3104 | Calgary | Alberta | Canada | T2V 1P9 |
| 44 | Site CA3242 | Abbotsford | British Columbia | Canada | V2S 3N5 |
| 45 | Site CA2646 | Kingston | Ontario | Canada | K7L 2V7 |
| 46 | Site CA166 | Toronto | Ontario | Canada | M4N 3M5 |
| 47 | Site CA3084 | Toronto | Ontario | Canada | M5G 2M9 |
| 48 | Site CA2984 | Granby | Quebec | Canada | J2G 8Z9 |
| 49 | Site CA170 | Montreal | Quebec | Canada | H3G 1A4 |
| 50 | Site DK3354 | Aalborg | Denmark | 9000 | |
| 51 | Site DK3356 | Aarhus | Denmark | 8200 | |
| 52 | Site DK1857 | Copenhagen | Denmark | 2200 | |
| 53 | Site DK1263 | Herlev | Denmark | 2730 | |
| 54 | Site FR1091 | Creteil | France | 94010 | |
| 55 | Site FR3009 | Lille | France | 59037 | |
| 56 | Site FR442 | Lyon Cedex 3 | France | 69437 | |
| 57 | Site FR3002 | Paris Cedex 10 | France | 75020 | |
| 58 | Site FR3003 | Poitiers Cedex | France | 86000 | |
| 59 | Site FR3000 | Rennes Cedex | France | 35033 | |
| 60 | Site FR3007 | Rouen | France | 76031 | |
| 61 | Site FR3005 | Suresnes Cedex | France | 92151 | |
| 62 | Site DE4000 | Nuertingen | Baden-Wuerttemberg | Germany | 72622 |
| 63 | Site DE2989 | Aachen | Germany | 51074 | |
| 64 | Site DE3287 | Bergisch Gladbach | Germany | D-51465 | |
| 65 | Site DE2993 | Bonn | Germany | 53105 | |
| 66 | Site DE2995 | Bonn | Germany | 53111 | |
| 67 | Site DE2994 | Bonn | Germany | 53117 | |
| 68 | Site DE2990 | Hamburg | Germany | 22081 | |
| 69 | Site DE3270 | Hannover | Germany | 30625 | |
| 70 | Site DE2992 | Reutlingen | Germany | 72764 | |
| 71 | Site DE3286 | Waldshut-Tiengen | Germany | 29761 | |
| 72 | Site DE2988 | Wuppertal | Germany | 42103 | |
| 73 | Site RO3042 | Bucharest | RO | Romania | 022328 |
| 74 | Site RO3039 | Bucharest | RO | Romania | 050659 |
| 75 | Site RO3035 | Bucharest | Romania | 041345 | |
| 76 | Site GB3029 | Bristol | UK | United Kingdom | BS2 8HW |
| 77 | Site GB3027 | London | UK | United Kingdom | SE19RT |
| 78 | Site GB3030 | London | UK | United Kingdom | SW17 0QT |
| 79 | Site GB3028 | Cardiff | Wales | United Kingdom | CF14 4XW |
| 80 | Site GB3244 | Belfast | United Kingdom | BT9 7AB | |
| 81 | Site GB2702 | Cambridge | United Kingdom | CB2 0QQ | |
| 82 | Site GB3166 | Glasgow | United Kingdom | G12 0YN | |
| 83 | Site GB1862 | Leicher | United Kingdom | LE5 4PW | |
| 84 | Site GB3163 | London | United Kingdom | NW1 2PG | |
| 85 | Site GB2624 | Manchester | United Kingdom | M20 4BX | |
| 86 | Site GB3355 | Merseyside | United Kingdom | CH63 4JY | |
| 87 | Site GB3245 | Northwood, Middlesex | United Kingdom | HA6 2RN | |
| 88 | Site GB3290 | Preston | United Kingdom | PR2 9HT |
Sponsors and Collaborators
- Astellas Pharma Inc
- Medivation LLC, a wholly owned subsidiary of Pfizer Inc.
Investigators
- Principal Investigator: Principal Investigator, Carolina Urologic Research Center
- Study Director: Associate Medical Science Director, Astellas Pharma Global Development
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.Responsible Party:
Astellas Pharma Inc
ClinicalTrials.gov Identifier:
NCT01288911
Other Study ID Numbers:
- 9785-CL-0222
- 2010-021868-15
First Posted:
Feb 3, 2011
Last Update Posted:
Jul 27, 2022
Last Verified:
Jul 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Astellas Pharma Inc
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Men with metastatic castration-resistant prostate cancer (mCRPC) were enrolled at 84 sites in a total of 8 countries. |
|---|---|
| Pre-assignment Detail | Participants were stratified by whether bilateral orchiectomy or receipt of luteinizing hormone-releasing hormone (LHRH) agonist/antagonist therapy started before or after the diagnosis of metastases and by site. |
| Arm/Group Title | Enzalutamide | Bicalutamide |
|---|---|---|
| Arm/Group Description | Participants received enzalutamide 160 mg orally once daily until confirmed radiographic disease progression, skeletal-related event or the initiation of a new antineoplastic therapy. | Participants received bicalutamide 50 mg orally once daily until confirmed radiographic disease progression, skeletal-related event or the initiation of a new antineoplastic therapy. |
| Period Title: Double-blind Period | ||
| STARTED | 184 | 191 |
| Received Treatment | 183 | 189 |
| COMPLETED | 42 | 9 |
| NOT COMPLETED | 142 | 182 |
| Period Title: Double-blind Period | ||
| STARTED | 42 | 9 |
| Received Treatment | 42 | 9 |
| COMPLETED | 0 | 0 |
| NOT COMPLETED | 42 | 9 |
Baseline Characteristics
| Arm/Group Title | Enzalutamide | Bicalutamide | Total |
|---|---|---|---|
| Arm/Group Description | Participants received enzalutamide 160 mg orally once daily until confirmed radiographic disease progression, skeletal-related event or the initiation of a new antineoplastic therapy. | Participants received bicalutamide 50 mg orally once daily until confirmed radiographic disease progression, skeletal-related event or the initiation of a new antineoplastic therapy. | Total of all reporting groups |
| Overall Participants | 184 | 191 | 375 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
70.3
(9.22)
|
71.1
(8.89)
|
70.7
(9.05)
|
| Age, Customized (participants) [Number] | |||
| < 65 years |
45
24.5%
|
47
24.6%
|
92
24.5%
|
| 65-75 years |
85
46.2%
|
80
41.9%
|
165
44%
|
| > 75 years |
54
29.3%
|
64
33.5%
|
118
31.5%
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
0
0%
|
0
0%
|
0
0%
|
| Male |
184
100%
|
191
100%
|
375
100%
|
| Race/Ethnicity, Customized (Count of Participants) | |||
| White |
172
93.5%
|
176
92.1%
|
348
92.8%
|
| Black or African American |
8
4.3%
|
10
5.2%
|
18
4.8%
|
| Asian |
3
1.6%
|
2
1%
|
5
1.3%
|
| Native Hawaiian or Other Pacific Islander |
1
0.5%
|
1
0.5%
|
2
0.5%
|
| Other |
0
0%
|
2
1%
|
2
0.5%
|
| Ethnicity (Count of Participants) | |||
| Not Hispanic or Latino |
184
100%
|
187
97.9%
|
371
98.9%
|
| Hispanic or Latino |
0
0%
|
4
2.1%
|
4
1.1%
|
| LHRH agonist/antagonist initiation or bilateral orchiectomy relative to diagnosis of metastasis (Count of Participants) | |||
| Before diagnosis of metastasis |
87
47.3%
|
76
39.8%
|
163
43.5%
|
| After diagnosis of metastasis |
97
52.7%
|
115
60.2%
|
212
56.5%
|
Outcome Measures
| Title | Progression Free Survival (PFS) Based on Independent Central Review (ICR) Assessment |
|---|---|
| Description | PFS is the time from randomization to the date of the first progression event detected. A progression event was defined as objective evidence of radiographic disease progression based on the assessments by the ICR, skeletal-related event, initiation of new antineoplastic therapy or death by any cause, whichever occurred first. Radiographic disease progression was defined as either a progression in soft tissue on computed tomography (CT)/magnetic resonance imaging (MRI) scan according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, and/or a progression in bone lesions on bone scan (≥ 2 new bone lesions) confirmed by the next bone scan. A skeletal-related event was any radiation therapy or surgery to bone, pathologic bone fracture, spinal cord compression or change in antineoplastic therapy to treat bone pain. The initiation of new antineoplastic therapy included any new therapy for the treatment of disease progression after the study drug administration started. |
| Time Frame | From randomization until the data cut-off date of 19 October 2014, median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set (all randomized participants) |
| Arm/Group Title | Enzalutamide | Bicalutamide |
|---|---|---|
| Arm/Group Description | Participants received enzalutamide 160 mg orally once daily until confirmed radiographic disease progression, skeletal-related event or the initiation of a new antineoplastic therapy. | Participants received bicalutamide 50 mg orally once daily until confirmed radiographic disease progression, skeletal-related event or the initiation of a new antineoplastic therapy. |
| Measure Participants | 184 | 191 |
| Median (95% Confidence Interval) [months] |
15.7
|
5.8
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Enzalutamide, Bicalutamide |
|---|---|---|
| Comments | PFS based on ICR Enzalutamide Vs. Bicalutamide. The (unstratified) log-rank test with an overall significance level of 0.05 (two-sided) was used to compare the PFS of enzalutamide to bicalutamide. The (unstratified) Cox proportional hazards model was used to estimate the hazard ratio of enzalutamide to bicalutamide, calculate the corresponding two-sided 95% confidence intervals and test the hypothesis that the hazard ratio is equal to 1. | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.44 | |
| Confidence Interval |
(2-Sided) 95% 0.34 to 0.57 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Estimated by use of Cox proportional hazards model. | |
| Title | PFS Based on Investigator Assessment |
|---|---|
| Description | PFS was calculated as the time from randomization to the date of the first progression event detected. A progression event was defined as objective evidence of radiographic disease progression based on the assessments by investigators, skeletal-related event, initiation of new antineoplastic therapy or death by any cause, whichever occurred first. Radiographic disease progression was defined as either a progression in soft tissue on CT/MRI scan according to RECIST 1.1, and/or a progression in bone lesions on bone scan (≥ 2 new bone lesions) confirmed by the next bone scan. A skeletal-related event was defined as radiation therapy or surgery to bone, pathologic bone fracture, spinal cord compression or change in antineoplastic therapy to treat bone pain. The initiation of new antineoplastic therapy included any new therapy for the treatment of disease progression after the study drug administration started. |
| Time Frame | From randomization until the data cut-off date of 19 October 2014, median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set |
| Arm/Group Title | Enzalutamide | Bicalutamide |
|---|---|---|
| Arm/Group Description | Participants received enzalutamide 160 mg orally once daily until confirmed radiographic disease progression, skeletal-related event or the initiation of a new antineoplastic therapy. | Participants received bicalutamide 50 mg orally once daily until confirmed radiographic disease progression, skeletal-related event or the initiation of a new antineoplastic therapy. |
| Measure Participants | 184 | 191 |
| Median (95% Confidence Interval) [months] |
15.3
|
5.7
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Enzalutamide, Bicalutamide |
|---|---|---|
| Comments | PFS on based investigator assessment Enzalutamide Vs. Bicalutamide. | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.42 | |
| Confidence Interval |
(2-Sided) 95% 0.33 to 0.55 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Estimated by use of Cox proportional hazards model. | |
| Title | Prostate-specific Antigen (PSA) Response by Week 13 |
|---|---|
| Description | The PSA response by Week 13 was defined as the percentage change from Baseline to the smallest PSA value after Baseline (i.e., a decrease of 100% represents the largest possible decrease to a value below the lower limit of quantification) and on or before day 99 (i.e., upper boundary of the Week 13 visit window). For participants with no decrease in PSA post-baseline by Week 13, the PSA response by Week 13 was the smallest increase in PSA up to day 99. For participants with no post-baseline PSA values up to day 99, the PSA response by Week 13 was set to missing. PSA was analyzed at a central laboratory. |
| Time Frame | Baseline to Week 13 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set with available PSA data |
| Arm/Group Title | Enzalutamide | Bicalutamide |
|---|---|---|
| Arm/Group Description | Participants received enzalutamide 160 mg orally once daily until confirmed radiographic disease progression, skeletal-related event or the initiation of a new antineoplastic therapy. | Participants received bicalutamide 50 mg orally once daily until confirmed radiographic disease progression, skeletal-related event or the initiation of a new antineoplastic therapy. |
| Measure Participants | 171 | 163 |
| Median (Full Range) [percent change] |
-89.03
|
0.36
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Enzalutamide, Bicalutamide |
|---|---|---|
| Comments | PSA Response Enzalutamide Vs. Bicalutamide. | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Wilcoxon rank sum test | |
| Comments | ||
| Title | Best PSA Response |
|---|---|
| Description | The best PSA response was defined as the percentage change from Baseline to the smallest PSA value after Baseline including PSA results from samples taken after the study drug was stopped. For participants with no decrease in PSA post-baseline, the best PSA response was the smallest increase in PSA. For participants with no post-baseline PSA values, the PSA response was set to missing. PSA was analyzed at a central laboratory. |
| Time Frame | Baseline to the data cutoff date of 19 October 2014, median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set with available PSA data |
| Arm/Group Title | Enzalutamide | Bicalutamide |
|---|---|---|
| Arm/Group Description | Participants received enzalutamide 160 mg orally once daily until confirmed radiographic disease progression, skeletal-related event or the initiation of a new antineoplastic therapy. | Participants received bicalutamide 50 mg orally once daily until confirmed radiographic disease progression, skeletal-related event or the initiation of a new antineoplastic therapy. |
| Measure Participants | 174 | 168 |
| Median (Full Range) [percent change] |
-92.96
|
0.18
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Enzalutamide, Bicalutamide |
|---|---|---|
| Comments | Best PSA Response Enzalutamide Vs. Bicalutamide. | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Wilcoxon rank sum test | |
| Comments | ||
| Title | Time to PSA Progression |
|---|---|
| Description | Time to PSA progression was calculated as the time interval from the date of randomization to the date of first observation of PSA progression. PSA progression was defined as a ≥ 25% increase and an absolute increase of ≥ 2 ng/mL above the nadir (or above the baseline value for participants who did not have a decline in PSA post-baseline values), and confirmed by a second consecutive PSA assessment at least 3 weeks later. For participants with no documented PSA progression, the time to PSA progression was censored on the date the last PSA sample was taken. |
| Time Frame | From randomization until the data cutoff date of 19 October 2014, median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set |
| Arm/Group Title | Enzalutamide | Bicalutamide |
|---|---|---|
| Arm/Group Description | Participants received enzalutamide 160 mg orally once daily until confirmed radiographic disease progression, skeletal-related event or the initiation of a new antineoplastic therapy. | Participants received bicalutamide 50 mg orally once daily until confirmed radiographic disease progression, skeletal-related event or the initiation of a new antineoplastic therapy. |
| Measure Participants | 184 | 191 |
| Median (95% Confidence Interval) [months] |
19.4
|
5.8
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Enzalutamide, Bicalutamide |
|---|---|---|
| Comments | Time to PSA progression Enzalutamide Vs. Bicalutamide. | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.28 | |
| Confidence Interval |
(2-Sided) 95% 0.20 to 0.39 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Estimated by use of Cox proportional hazards model. | |
| Title | Time to PSA ≤ 4 ng/mL |
|---|---|
| Description | Time to PSA ≤ 4 ng/mL was defined as the time interval from the date of randomization to the first date a decline in PSA to a result of 4 ng/mL or below was recorded. In participants without PSA results ≤ 4 ng/mL, the time to PSA ≤ 4 ng/mL was censored on the date of the last PSA sample taken. Participants with a PSA result ≤ 4 ng/mL at Baseline, participants with no Baseline PSA and participants with no post-baseline PSA results were censored on the date of randomization |
| Time Frame | From randomization until the data cutoff date of 19 October 2014, median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set |
| Arm/Group Title | Enzalutamide | Bicalutamide |
|---|---|---|
| Arm/Group Description | Participants received enzalutamide 160 mg orally once daily until confirmed radiographic disease progression, skeletal-related event or the initiation of a new antineoplastic therapy. | Participants received bicalutamide 50 mg orally once daily until confirmed radiographic disease progression, skeletal-related event or the initiation of a new antineoplastic therapy. |
| Measure Participants | 184 | 191 |
| Median (95% Confidence Interval) [months] |
3.0
|
NA
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Enzalutamide, Bicalutamide |
|---|---|---|
| Comments | Time to PSA Enzalutamide Vs. Bicalutamide. | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 5.07 | |
| Confidence Interval |
(2-Sided) 95% 3.18 to 8.09 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Estimated by use of Cox proportional hazards model. | |
| Title | Time to ≥ 30% PSA Decline From Baseline |
|---|---|
| Description | The time to ≥ 30% PSA decline from Baseline was defined as the time interval from the date of randomization to the first date a PSA decline from Baseline of at least 30% was recorded. In participants without ≥ 30% PSA decline from Baseline, the time to ≥ 30% PSA decline from Baseline was censored on the date of the last PSA sample taken. Participants who had no Baseline PSA and participants with no post-baseline PSA results were censored on the date of randomization. |
| Time Frame | From randomization until the data cutoff date of 19 October 2014, median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set |
| Arm/Group Title | Enzalutamide | Bicalutamide |
|---|---|---|
| Arm/Group Description | Participants received enzalutamide 160 mg orally once daily until confirmed radiographic disease progression, skeletal-related event or the initiation of a new antineoplastic therapy. | Participants received bicalutamide 50 mg orally once daily until confirmed radiographic disease progression, skeletal-related event or the initiation of a new antineoplastic therapy. |
| Measure Participants | 184 | 191 |
| Median (95% Confidence Interval) [months] |
2.8
|
NA
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Enzalutamide, Bicalutamide |
|---|---|---|
| Comments | Time to ≥ 30% PSA decline from baseline Enzalutamide Vs. Bicalutamide. | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 5.55 | |
| Confidence Interval |
(2-Sided) 95% 3.96 to 7.79 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Estimated by use of Cox proportional hazards model. | |
| Title | Time to ≥ 50% PSA Decline From Baseline |
|---|---|
| Description | The time to ≥ 50% PSA decline from Baseline was defined as the time interval from the date of randomization to the first date a PSA decline from Baseline of at least 50% was recorded. In participants without ≥ 50% PSA decline from Baseline, the time to ≥ 50% PSA decline from Baseline was censored on the date of the last PSA sample taken. Participants who had no Baseline PSA and participants with no post-baseline PSA results were censored on the date of randomization. |
| Time Frame | From randomization until the data cutoff date of 19 October 2014, median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set |
| Arm/Group Title | Enzalutamide | Bicalutamide |
|---|---|---|
| Arm/Group Description | Participants received enzalutamide 160 mg orally once daily until confirmed radiographic disease progression, skeletal-related event or the initiation of a new antineoplastic therapy. | Participants received bicalutamide 50 mg orally once daily until confirmed radiographic disease progression, skeletal-related event or the initiation of a new antineoplastic therapy. |
| Measure Participants | 184 | 191 |
| Median (95% Confidence Interval) [months] |
2.8
|
NA
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Enzalutamide, Bicalutamide |
|---|---|---|
| Comments | Time to ≥ 50% PSA decline from baseline Enzalutamide Vs. Bicalutamide. | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 7.01 | |
| Confidence Interval |
(2-Sided) 95% 4.83 to 10.16 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Estimated by use of Cox proportional hazards model. | |
| Title | Time to ≥ 90% PSA Decline From Baseline |
|---|---|
| Description | The time to ≥ 90% PSA decline from Baseline was defined as the time interval from the date of randomization to the first date a PSA decline from Baseline of at least 90% was recorded. In participants without ≥ 90% PSA decline from Baseline, the time to ≥ 90% PSA decline from Baseline was censored on the date of the last PSA sample taken. Participants who had no Baseline PSA and participants with no post-baseline PSA results were censored on the date of randomization. |
| Time Frame | From randomization until the data cutoff date of 19 October 2014, median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set |
| Arm/Group Title | Enzalutamide | Bicalutamide |
|---|---|---|
| Arm/Group Description | Participants received enzalutamide 160 mg orally once daily until confirmed radiographic disease progression, skeletal-related event or the initiation of a new antineoplastic therapy. | Participants received bicalutamide 50 mg orally once daily until confirmed radiographic disease progression, skeletal-related event or the initiation of a new antineoplastic therapy. |
| Measure Participants | 184 | 191 |
| Median (95% Confidence Interval) [months] |
5.4
|
NA
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Enzalutamide, Bicalutamide |
|---|---|---|
| Comments | Time to ≥ 90% PSA decline from baseline Enzalutamide Vs. Bicalutamide. | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 13.91 | |
| Confidence Interval |
(2-Sided) 95% 7.23 to 26.79 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Estimated by use of Cox proportional hazards model. | |
| Title | Radiographic PFS Based on ICR Assessment |
|---|---|
| Description | Radiographic PFS was calculated as the time interval from the date of randomization to the first date of radiographic disease progression. Radiographic disease progression was defined as either a progression in soft tissue on CT/MRI scan according to RECIST 1.1, and/or a progression in bone lesions (a minimum of 2 new bone lesions as compared to previous scan) on bone scan and confirmed by the next bone scan. |
| Time Frame | From randomization until the data cutoff date of 19 October 2014, median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set |
| Arm/Group Title | Enzalutamide | Bicalutamide |
|---|---|---|
| Arm/Group Description | Participants received enzalutamide 160 mg orally once daily until confirmed radiographic disease progression, skeletal-related event or the initiation of a new antineoplastic therapy. | Participants received bicalutamide 50 mg orally once daily until confirmed radiographic disease progression, skeletal-related event or the initiation of a new antineoplastic therapy. |
| Measure Participants | 184 | 191 |
| Median (95% Confidence Interval) [months] |
NA
|
16.4
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Enzalutamide, Bicalutamide |
|---|---|---|
| Comments | Radiographic PFS based on ICR Enzalutamide Vs. Bicalutamide. | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0002 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.51 | |
| Confidence Interval |
(2-Sided) 95% 0.36 to 0.74 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Estimated by use of Cox proportional hazards model. | |
| Title | Percentage of Participants With an Objective Response |
|---|---|
| Description | Response assessments were reported by ICR for target lesions in soft tissues and non-target lesions in soft tissues based on CT and/or MRI according to RECIST version 1.1. Objective response was defined as the number of participants achieving either a complete response (CR) or a partial response (PR) based on participant's best overall response assessed at the end of the treatment. |
| Time Frame | From randomization until the data cutoff date of 19 October 2014, median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set |
| Arm/Group Title | Enzalutamide | Bicalutamide |
|---|---|---|
| Arm/Group Description | Participants received enzalutamide 160 mg orally once daily until confirmed radiographic disease progression, skeletal-related event or the initiation of a new antineoplastic therapy. | Participants received bicalutamide 50 mg orally once daily until confirmed radiographic disease progression, skeletal-related event or the initiation of a new antineoplastic therapy. |
| Measure Participants | 184 | 191 |
| Number [percentage of participants] |
15.8
8.6%
|
2.6
1.4%
|
| Title | Percentage of Participants With Adverse Events |
|---|---|
| Description | A serious adverse event was defined as any untoward medical occurrence that at any dose: Resulted in death Was life threatening Resulted in persistent or significant disability/incapacity Resulted in congenital anomaly or birth defect Required inpatient hospitalization or led to prolongation of hospitalization Other medically important events. Treatment-related indicates adverse events assessed by the Investigator as probably or possibly related to study treatment. Treatment emergent adverse events (TEAEs) were defined as adverse events (AEs) that started or worsened after starting administration of study drug through end of the study (i.e., the treatment-emergent period). |
| Time Frame | From initiation of study drug up to 30 days after last dose of study drug or the 30-day safety follow-up visit, whichever was last (Median duration of treatment was 11.6 months in enzalutamide arm and 5.8 in bicalutamide arm, 12.6 in the total arm). |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set (all participants who had initiated at least 1 dose of study drug) |
| Arm/Group Title | Enzalutamide | Bicalutamide | Total Enzalutamide |
|---|---|---|---|
| Arm/Group Description | Participants received enzalutamide 160 mg orally once daily until confirmed radiographic disease progression, skeletal-related event or the initiation of a new antineoplastic therapy. | Participants received bicalutamide 50 mg orally once daily until confirmed radiographic disease progression, skeletal-related event or the initiation of a new antineoplastic therapy. | Participants received enzalutamide in the double-blind and/or open-label period (including participants who switched from bicalutamide to enzalutamide). |
| Measure Participants | 183 | 189 | 192 |
| TEAEs |
94.5
51.4%
|
94.2
49.3%
|
94.8
25.3%
|
| Related TEAEs |
66.7
36.3%
|
49.7
26%
|
67.2
17.9%
|
| Deaths |
5.5
3%
|
1.6
0.8%
|
5.7
1.5%
|
| Serious TEAEs |
33.3
18.1%
|
23.8
12.5%
|
36.5
9.7%
|
| Drug regimen-related serious TEAEs |
6.6
3.6%
|
3.2
1.7%
|
6.8
1.8%
|
| TEAEs leading to discontinuation |
29.5
16%
|
23.8
12.5%
|
31.3
8.3%
|
| Drug regimen-related TEAEs leading to discon. |
7.7
4.2%
|
5.3
2.8%
|
7.8
2.1%
|
| TEAEs leading to study drug interruption |
10.4
5.7%
|
7.9
4.1%
|
10.4
2.8%
|
Adverse Events
| Time Frame | From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. | |||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | The total number of deaths (all causes) includes deaths reported after the time frame above. | |||||||
| Arm/Group Title | Double-blind Period: Enzalutamide | Double-blind Period: Bicalutamide | Open-label Period: Enzalutamide/Enzalutamide | Open-label Period: Bicalutamide/Enzalutamide | ||||
| Arm/Group Description | Participants received enzalutamide 160 mg orally once daily in the double-blind period until confirmed radiographic disease progression, skeletal-related event or the initiation of a new antineoplastic therapy. | Participants received bicalutamide 50 mg orally once daily in the double-blind period until confirmed radiographic disease progression, skeletal-related event or the initiation of a new antineoplastic therapy. | Participants received enzalutamide in the double-blind period and received enzalutamide in the open-label period as well. | Participants received bicalutamide in the double-blind period and switched over to enzalutamide in the open-label period. | ||||
All Cause Mortality |
||||||||
| Double-blind Period: Enzalutamide | Double-blind Period: Bicalutamide | Open-label Period: Enzalutamide/Enzalutamide | Open-label Period: Bicalutamide/Enzalutamide | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 11/141 (7.8%) | 7/180 (3.9%) | 0/42 (0%) | 1/9 (11.1%) | ||||
Serious Adverse Events |
||||||||
| Double-blind Period: Enzalutamide | Double-blind Period: Bicalutamide | Open-label Period: Enzalutamide/Enzalutamide | Open-label Period: Bicalutamide/Enzalutamide | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 49/141 (34.8%) | 43/180 (23.9%) | 18/42 (42.9%) | 4/9 (44.4%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Anaemia | 5/141 (3.5%) | 5 | 0/180 (0%) | 0 | 1/42 (2.4%) | 1 | 0/9 (0%) | 0 |
| Febrile bone marrow aplasia | 0/141 (0%) | 0 | 1/180 (0.6%) | 1 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Pancytopenia | 1/141 (0.7%) | 1 | 1/180 (0.6%) | 1 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Cardiac disorders | ||||||||
| Acute myocardial infarction | 1/141 (0.7%) | 1 | 0/180 (0%) | 0 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Angina pectoris | 0/141 (0%) | 0 | 0/180 (0%) | 0 | 1/42 (2.4%) | 1 | 0/9 (0%) | 0 |
| Aortic valve stenosis | 0/141 (0%) | 0 | 0/180 (0%) | 0 | 1/42 (2.4%) | 1 | 0/9 (0%) | 0 |
| Arteriosclerosis coronary artery | 0/141 (0%) | 0 | 0/180 (0%) | 0 | 1/42 (2.4%) | 1 | 0/9 (0%) | 0 |
| Atrial fibrillation | 2/141 (1.4%) | 2 | 1/180 (0.6%) | 1 | 1/42 (2.4%) | 1 | 0/9 (0%) | 0 |
| Atrioventricular block | 0/141 (0%) | 0 | 0/180 (0%) | 0 | 0/42 (0%) | 0 | 1/9 (11.1%) | 1 |
| Atrioventricular block complete | 0/141 (0%) | 0 | 0/180 (0%) | 0 | 1/42 (2.4%) | 1 | 0/9 (0%) | 0 |
| Bradycardia | 0/141 (0%) | 0 | 0/180 (0%) | 0 | 1/42 (2.4%) | 1 | 1/9 (11.1%) | 1 |
| Cardiac failure congestive | 3/141 (2.1%) | 3 | 3/180 (1.7%) | 3 | 2/42 (4.8%) | 2 | 0/9 (0%) | 0 |
| Cardiogenic shock | 0/141 (0%) | 0 | 0/180 (0%) | 0 | 0/42 (0%) | 0 | 1/9 (11.1%) | 1 |
| Coronary artery disease | 0/141 (0%) | 0 | 0/180 (0%) | 0 | 1/42 (2.4%) | 1 | 0/9 (0%) | 0 |
| Mitral valve incompetence | 0/141 (0%) | 0 | 1/180 (0.6%) | 1 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Myocardial infarction | 4/141 (2.8%) | 4 | 0/180 (0%) | 0 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Sick sinus syndrome | 0/141 (0%) | 0 | 1/180 (0.6%) | 1 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Sinus tachycardia | 0/141 (0%) | 0 | 0/180 (0%) | 0 | 1/42 (2.4%) | 1 | 0/9 (0%) | 0 |
| Supraventricular tachycardia | 0/141 (0%) | 0 | 1/180 (0.6%) | 1 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Ventricular extrasystoles | 1/141 (0.7%) | 1 | 0/180 (0%) | 0 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Ventricular fibrillation | 0/141 (0%) | 0 | 0/180 (0%) | 0 | 0/42 (0%) | 0 | 1/9 (11.1%) | 1 |
| Ventricular tachyarrhythmia | 1/141 (0.7%) | 1 | 0/180 (0%) | 0 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Congenital, familial and genetic disorders | ||||||||
| Arteriovenous malformation | 1/141 (0.7%) | 1 | 0/180 (0%) | 0 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Gastrointestinal disorders | ||||||||
| Abdominal pain | 2/141 (1.4%) | 2 | 2/180 (1.1%) | 2 | 2/42 (4.8%) | 2 | 0/9 (0%) | 0 |
| Constipation | 2/141 (1.4%) | 2 | 2/180 (1.1%) | 2 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Diarrhoea | 0/141 (0%) | 0 | 1/180 (0.6%) | 1 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Diverticulum | 0/141 (0%) | 0 | 1/180 (0.6%) | 1 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Gastrointestinal haemorrhage | 0/141 (0%) | 0 | 0/180 (0%) | 0 | 1/42 (2.4%) | 1 | 0/9 (0%) | 0 |
| Haematemesis | 1/141 (0.7%) | 1 | 0/180 (0%) | 0 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Haematochezia | 1/141 (0.7%) | 1 | 0/180 (0%) | 0 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Lower gastrointestinal haemorrhage | 0/141 (0%) | 0 | 0/180 (0%) | 0 | 1/42 (2.4%) | 1 | 0/9 (0%) | 0 |
| Rectal haemorrhage | 1/141 (0.7%) | 1 | 1/180 (0.6%) | 1 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Salivary gland calculus | 0/141 (0%) | 0 | 0/180 (0%) | 0 | 1/42 (2.4%) | 1 | 0/9 (0%) | 0 |
| Vomiting | 0/141 (0%) | 0 | 1/180 (0.6%) | 1 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| General disorders | ||||||||
| Asthenia | 1/141 (0.7%) | 1 | 0/180 (0%) | 0 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Fatigue | 1/141 (0.7%) | 1 | 0/180 (0%) | 0 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| General physical health deterioration | 1/141 (0.7%) | 1 | 0/180 (0%) | 0 | 2/42 (4.8%) | 2 | 0/9 (0%) | 0 |
| Generalised oedema | 0/141 (0%) | 0 | 1/180 (0.6%) | 1 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Non-cardiac chest pain | 1/141 (0.7%) | 1 | 0/180 (0%) | 0 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Pain | 0/141 (0%) | 0 | 1/180 (0.6%) | 2 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Pyrexia | 0/141 (0%) | 0 | 1/180 (0.6%) | 1 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Systemic inflammatory response syndrome | 1/141 (0.7%) | 1 | 0/180 (0%) | 0 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Hepatobiliary disorders | ||||||||
| Cholelithiasis | 0/141 (0%) | 0 | 0/180 (0%) | 0 | 1/42 (2.4%) | 1 | 0/9 (0%) | 0 |
| Infections and infestations | ||||||||
| Abscess of salivary gland | 0/141 (0%) | 0 | 0/180 (0%) | 0 | 1/42 (2.4%) | 1 | 0/9 (0%) | 0 |
| Arthritis bacterial | 0/141 (0%) | 0 | 1/180 (0.6%) | 1 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Bacteraemia | 1/141 (0.7%) | 1 | 0/180 (0%) | 0 | 0/42 (0%) | 0 | 1/9 (11.1%) | 1 |
| Cellulitis | 1/141 (0.7%) | 1 | 0/180 (0%) | 0 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Cystitis | 1/141 (0.7%) | 2 | 0/180 (0%) | 0 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Diverticulitis | 1/141 (0.7%) | 1 | 0/180 (0%) | 0 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Gastroenteritis | 1/141 (0.7%) | 1 | 0/180 (0%) | 0 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Gastroenteritis viral | 0/141 (0%) | 0 | 1/180 (0.6%) | 1 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Infection | 0/141 (0%) | 0 | 0/180 (0%) | 0 | 0/42 (0%) | 0 | 1/9 (11.1%) | 1 |
| Infective exacerbation of chronic obstructive airways disease | 0/141 (0%) | 0 | 1/180 (0.6%) | 1 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Pneumonia | 1/141 (0.7%) | 1 | 2/180 (1.1%) | 2 | 1/42 (2.4%) | 1 | 0/9 (0%) | 0 |
| Urosepsis | 2/141 (1.4%) | 2 | 0/180 (0%) | 0 | 1/42 (2.4%) | 1 | 0/9 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||||
| Ankle fracture | 0/141 (0%) | 0 | 1/180 (0.6%) | 1 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Craniocerebral injury | 1/141 (0.7%) | 1 | 0/180 (0%) | 0 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Fall | 1/141 (0.7%) | 1 | 0/180 (0%) | 0 | 0/42 (0%) | 0 | 1/9 (11.1%) | 1 |
| Hip fracture | 1/141 (0.7%) | 1 | 1/180 (0.6%) | 1 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Rib fracture | 2/141 (1.4%) | 2 | 0/180 (0%) | 0 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Investigations | ||||||||
| Alanine aminotransferase increased | 0/141 (0%) | 0 | 1/180 (0.6%) | 1 | 1/42 (2.4%) | 1 | 0/9 (0%) | 0 |
| Arteriogram coronary | 1/141 (0.7%) | 1 | 0/180 (0%) | 0 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Aspartate aminotransferase increased | 0/141 (0%) | 0 | 1/180 (0.6%) | 1 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Blood creatinine increased | 1/141 (0.7%) | 1 | 1/180 (0.6%) | 1 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Eastern Cooperative Oncology Group performance status worsened | 0/141 (0%) | 0 | 1/180 (0.6%) | 1 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Gamma-glutamyltransferase increased | 1/141 (0.7%) | 1 | 1/180 (0.6%) | 1 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Liver function test abnormal | 0/141 (0%) | 0 | 0/180 (0%) | 0 | 2/42 (4.8%) | 2 | 0/9 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||||
| Dehydration | 2/141 (1.4%) | 2 | 1/180 (0.6%) | 1 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Hyperkalaemia | 0/141 (0%) | 0 | 2/180 (1.1%) | 2 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Hyponatraemia | 0/141 (0%) | 0 | 1/180 (0.6%) | 1 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||||
| Arthralgia | 0/141 (0%) | 0 | 1/180 (0.6%) | 1 | 0/42 (0%) | 0 | 1/9 (11.1%) | 1 |
| Back pain | 1/141 (0.7%) | 2 | 0/180 (0%) | 0 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Bone pain | 0/141 (0%) | 0 | 1/180 (0.6%) | 1 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Joint lock | 1/141 (0.7%) | 1 | 0/180 (0%) | 0 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Lumbar spinal stenosis | 0/141 (0%) | 0 | 1/180 (0.6%) | 1 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Muscular weakness | 1/141 (0.7%) | 1 | 0/180 (0%) | 0 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Musculoskeletal chest pain | 1/141 (0.7%) | 1 | 0/180 (0%) | 0 | 1/42 (2.4%) | 1 | 0/9 (0%) | 0 |
| Osteoarthritis | 1/141 (0.7%) | 1 | 0/180 (0%) | 0 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Pain in extremity | 0/141 (0%) | 0 | 1/180 (0.6%) | 1 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Pathological fracture | 5/141 (3.5%) | 6 | 2/180 (1.1%) | 2 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Spinal column stenosis | 0/141 (0%) | 0 | 1/180 (0.6%) | 1 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
| Adenocarcinoma of colon | 0/141 (0%) | 0 | 0/180 (0%) | 0 | 1/42 (2.4%) | 1 | 0/9 (0%) | 0 |
| Basal cell carcinoma | 1/141 (0.7%) | 4 | 1/180 (0.6%) | 1 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Basosquamous carcinoma of skin | 1/141 (0.7%) | 1 | 0/180 (0%) | 0 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Bladder cancer | 1/141 (0.7%) | 1 | 0/180 (0%) | 0 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Bowen's disease | 0/141 (0%) | 0 | 1/180 (0.6%) | 1 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Brain neoplasm malignant | 1/141 (0.7%) | 1 | 0/180 (0%) | 0 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Cancer pain | 1/141 (0.7%) | 1 | 0/180 (0%) | 0 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Chronic lymphocytic leukaemia | 0/141 (0%) | 0 | 0/180 (0%) | 0 | 1/42 (2.4%) | 1 | 0/9 (0%) | 0 |
| Colon cancer | 0/141 (0%) | 0 | 1/180 (0.6%) | 1 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Gastric cancer | 0/141 (0%) | 0 | 1/180 (0.6%) | 1 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Gastrointestinal tract adenoma | 0/141 (0%) | 0 | 1/180 (0.6%) | 1 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Lung adenocarcinoma | 1/141 (0.7%) | 1 | 0/180 (0%) | 0 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Lung neoplasm malignant | 1/141 (0.7%) | 1 | 0/180 (0%) | 0 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Malignant neoplasm of conjunctiva | 1/141 (0.7%) | 1 | 0/180 (0%) | 0 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Malignant neoplasm progression | 2/141 (1.4%) | 2 | 1/180 (0.6%) | 1 | 3/42 (7.1%) | 3 | 0/9 (0%) | 0 |
| Metastases to central nervous system | 0/141 (0%) | 0 | 1/180 (0.6%) | 1 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Metastases to lung | 1/141 (0.7%) | 1 | 0/180 (0%) | 0 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Metastases to spine | 0/141 (0%) | 0 | 1/180 (0.6%) | 1 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Metastatic pain | 1/141 (0.7%) | 1 | 1/180 (0.6%) | 1 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Myelodysplastic syndrome | 1/141 (0.7%) | 1 | 0/180 (0%) | 0 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Neuroendocrine carcinoma | 1/141 (0.7%) | 1 | 0/180 (0%) | 0 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Paraneoplastic syndrome | 1/141 (0.7%) | 1 | 0/180 (0%) | 0 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Penile cancer | 1/141 (0.7%) | 1 | 0/180 (0%) | 0 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Skin cancer | 1/141 (0.7%) | 1 | 0/180 (0%) | 0 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Squamous cell carcinoma | 0/141 (0%) | 0 | 0/180 (0%) | 0 | 1/42 (2.4%) | 1 | 0/9 (0%) | 0 |
| Squamous cell carcinoma of skin | 0/141 (0%) | 0 | 0/180 (0%) | 0 | 2/42 (4.8%) | 3 | 0/9 (0%) | 0 |
| Superficial spreading melanoma stage unspecified | 1/141 (0.7%) | 1 | 0/180 (0%) | 0 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Ureteric cancer | 0/141 (0%) | 0 | 1/180 (0.6%) | 1 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Nervous system disorders | ||||||||
| Convulsion | 2/141 (1.4%) | 2 | 0/180 (0%) | 0 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Epiduritis | 1/141 (0.7%) | 1 | 0/180 (0%) | 0 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Hypoglycaemic seizure | 0/141 (0%) | 0 | 1/180 (0.6%) | 1 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Incoherent | 0/141 (0%) | 0 | 0/180 (0%) | 0 | 0/42 (0%) | 0 | 1/9 (11.1%) | 1 |
| Lacunar infarction | 1/141 (0.7%) | 1 | 0/180 (0%) | 0 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Paraplegia | 1/141 (0.7%) | 1 | 0/180 (0%) | 0 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Presyncope | 0/141 (0%) | 0 | 1/180 (0.6%) | 1 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Spinal cord compression | 1/141 (0.7%) | 1 | 1/180 (0.6%) | 1 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Syncope | 0/141 (0%) | 0 | 1/180 (0.6%) | 1 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Transient ischaemic attack | 1/141 (0.7%) | 1 | 0/180 (0%) | 0 | 1/42 (2.4%) | 2 | 1/9 (11.1%) | 1 |
| Tremor | 0/141 (0%) | 0 | 1/180 (0.6%) | 1 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Renal and urinary disorders | ||||||||
| Acute prerenal failure | 1/141 (0.7%) | 1 | 0/180 (0%) | 0 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Bladder obstruction | 0/141 (0%) | 0 | 1/180 (0.6%) | 1 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Bladder outlet obstruction | 0/141 (0%) | 0 | 1/180 (0.6%) | 1 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Dysuria | 0/141 (0%) | 0 | 1/180 (0.6%) | 1 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Haematuria | 2/141 (1.4%) | 2 | 1/180 (0.6%) | 1 | 2/42 (4.8%) | 4 | 0/9 (0%) | 0 |
| Hydronephrosis | 0/141 (0%) | 0 | 2/180 (1.1%) | 2 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Obstructive uropathy | 1/141 (0.7%) | 1 | 0/180 (0%) | 0 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Postrenal failure | 0/141 (0%) | 0 | 2/180 (1.1%) | 2 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Renal colic | 1/141 (0.7%) | 1 | 0/180 (0%) | 0 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Renal failure | 0/141 (0%) | 0 | 1/180 (0.6%) | 1 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Renal failure acute | 2/141 (1.4%) | 2 | 0/180 (0%) | 0 | 0/42 (0%) | 0 | 1/9 (11.1%) | 1 |
| Renal impairment | 0/141 (0%) | 0 | 0/180 (0%) | 0 | 1/42 (2.4%) | 1 | 0/9 (0%) | 0 |
| Stress urinary incontinence | 1/141 (0.7%) | 2 | 0/180 (0%) | 0 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Ureteric dilatation | 0/141 (0%) | 0 | 1/180 (0.6%) | 1 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Urethral obstruction | 0/141 (0%) | 0 | 1/180 (0.6%) | 1 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Urinary retention | 0/141 (0%) | 0 | 2/180 (1.1%) | 2 | 2/42 (4.8%) | 2 | 0/9 (0%) | 0 |
| Urinary tract obstruction | 1/141 (0.7%) | 1 | 0/180 (0%) | 0 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Reproductive system and breast disorders | ||||||||
| Prostatic obstruction | 0/141 (0%) | 0 | 0/180 (0%) | 0 | 1/42 (2.4%) | 1 | 0/9 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Acute respiratory distress syndrome | 0/141 (0%) | 0 | 1/180 (0.6%) | 1 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Acute respiratory failure | 1/141 (0.7%) | 1 | 0/180 (0%) | 0 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Dyspnoea | 2/141 (1.4%) | 2 | 1/180 (0.6%) | 1 | 1/42 (2.4%) | 1 | 0/9 (0%) | 0 |
| Hypoxia | 0/141 (0%) | 0 | 1/180 (0.6%) | 1 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Pleural effusion | 0/141 (0%) | 0 | 1/180 (0.6%) | 1 | 1/42 (2.4%) | 1 | 0/9 (0%) | 0 |
| Pleuritic pain | 0/141 (0%) | 0 | 1/180 (0.6%) | 1 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Pneumonia aspiration | 2/141 (1.4%) | 2 | 1/180 (0.6%) | 1 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Pneumothorax | 1/141 (0.7%) | 1 | 0/180 (0%) | 0 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Pulmonary fibrosis | 1/141 (0.7%) | 1 | 0/180 (0%) | 0 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Surgical and medical procedures | ||||||||
| Transurethral prostatectomy | 0/141 (0%) | 0 | 0/180 (0%) | 0 | 1/42 (2.4%) | 1 | 0/9 (0%) | 0 |
| Vascular disorders | ||||||||
| Aortic stenosis | 2/141 (1.4%) | 2 | 0/180 (0%) | 0 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Hypotension | 1/141 (0.7%) | 1 | 0/180 (0%) | 0 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Orthostatic hypotension | 1/141 (0.7%) | 1 | 0/180 (0%) | 0 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Peripheral artery stenosis | 0/141 (0%) | 0 | 1/180 (0.6%) | 1 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
| Venous thrombosis limb | 0/141 (0%) | 0 | 1/180 (0.6%) | 1 | 0/42 (0%) | 0 | 0/9 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||||
| Double-blind Period: Enzalutamide | Double-blind Period: Bicalutamide | Open-label Period: Enzalutamide/Enzalutamide | Open-label Period: Bicalutamide/Enzalutamide | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 123/141 (87.2%) | 149/180 (82.8%) | 42/42 (100%) | 9/9 (100%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Anaemia | 10/141 (7.1%) | 10 | 5/180 (2.8%) | 7 | 4/42 (9.5%) | 4 | 1/9 (11.1%) | 1 |
| Cardiac disorders | ||||||||
| Angina pectoris | 0/141 (0%) | 0 | 0/180 (0%) | 0 | 1/42 (2.4%) | 1 | 1/9 (11.1%) | 1 |
| Palpitations | 2/141 (1.4%) | 2 | 1/180 (0.6%) | 1 | 0/42 (0%) | 0 | 1/9 (11.1%) | 1 |
| Eye disorders | ||||||||
| Cataract | 0/141 (0%) | 0 | 0/180 (0%) | 0 | 0/42 (0%) | 0 | 1/9 (11.1%) | 1 |
| Glaucoma | 0/141 (0%) | 0 | 0/180 (0%) | 0 | 0/42 (0%) | 0 | 1/9 (11.1%) | 1 |
| Ocular hyperaemia | 0/141 (0%) | 0 | 0/180 (0%) | 0 | 0/42 (0%) | 0 | 1/9 (11.1%) | 1 |
| Gastrointestinal disorders | ||||||||
| Abdominal pain | 6/141 (4.3%) | 6 | 7/180 (3.9%) | 7 | 3/42 (7.1%) | 4 | 1/9 (11.1%) | 1 |
| Constipation | 19/141 (13.5%) | 21 | 24/180 (13.3%) | 25 | 5/42 (11.9%) | 7 | 0/9 (0%) | 0 |
| Diarrhoea | 16/141 (11.3%) | 18 | 15/180 (8.3%) | 18 | 5/42 (11.9%) | 6 | 2/9 (22.2%) | 2 |
| Dyspepsia | 5/141 (3.5%) | 6 | 4/180 (2.2%) | 4 | 1/42 (2.4%) | 1 | 2/9 (22.2%) | 2 |
| Haemorrhoids | 1/141 (0.7%) | 1 | 1/180 (0.6%) | 1 | 0/42 (0%) | 0 | 1/9 (11.1%) | 1 |
| Nausea | 18/141 (12.8%) | 22 | 33/180 (18.3%) | 36 | 10/42 (23.8%) | 11 | 0/9 (0%) | 0 |
| Rectal haemorrhage | 4/141 (2.8%) | 4 | 1/180 (0.6%) | 1 | 1/42 (2.4%) | 1 | 1/9 (11.1%) | 1 |
| Vomiting | 5/141 (3.5%) | 5 | 9/180 (5%) | 10 | 1/42 (2.4%) | 1 | 0/9 (0%) | 0 |
| General disorders | ||||||||
| Asthenia | 8/141 (5.7%) | 10 | 7/180 (3.9%) | 7 | 2/42 (4.8%) | 2 | 0/9 (0%) | 0 |
| Fatigue | 35/141 (24.8%) | 40 | 38/180 (21.1%) | 45 | 18/42 (42.9%) | 24 | 3/9 (33.3%) | 3 |
| Oedema peripheral | 10/141 (7.1%) | 10 | 13/180 (7.2%) | 13 | 5/42 (11.9%) | 5 | 0/9 (0%) | 0 |
| Pain | 1/141 (0.7%) | 1 | 8/180 (4.4%) | 8 | 2/42 (4.8%) | 2 | 1/9 (11.1%) | 1 |
| Infections and infestations | ||||||||
| Bronchitis | 1/141 (0.7%) | 1 | 2/180 (1.1%) | 2 | 3/42 (7.1%) | 4 | 0/9 (0%) | 0 |
| Influenza | 3/141 (2.1%) | 4 | 4/180 (2.2%) | 4 | 1/42 (2.4%) | 1 | 1/9 (11.1%) | 1 |
| Nasopharyngitis | 11/141 (7.8%) | 13 | 7/180 (3.9%) | 8 | 7/42 (16.7%) | 9 | 1/9 (11.1%) | 1 |
| Osteomyelitis | 0/141 (0%) | 0 | 0/180 (0%) | 0 | 1/42 (2.4%) | 1 | 1/9 (11.1%) | 1 |
| Scrotal infection | 0/141 (0%) | 0 | 0/180 (0%) | 0 | 0/42 (0%) | 0 | 1/9 (11.1%) | 1 |
| Urinary tract infection | 7/141 (5%) | 8 | 3/180 (1.7%) | 3 | 4/42 (9.5%) | 4 | 0/9 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||||
| Arthropod bite | 0/141 (0%) | 0 | 0/180 (0%) | 0 | 3/42 (7.1%) | 3 | 0/9 (0%) | 0 |
| Fall | 9/141 (6.4%) | 11 | 6/180 (3.3%) | 7 | 4/42 (9.5%) | 6 | 2/9 (22.2%) | 2 |
| Rib fracture | 1/141 (0.7%) | 1 | 0/180 (0%) | 0 | 2/42 (4.8%) | 2 | 1/9 (11.1%) | 1 |
| Investigations | ||||||||
| Blood alkaline phosphatase increased | 3/141 (2.1%) | 4 | 5/180 (2.8%) | 6 | 0/42 (0%) | 0 | 1/9 (11.1%) | 1 |
| Blood urea increased | 0/141 (0%) | 0 | 3/180 (1.7%) | 3 | 1/42 (2.4%) | 1 | 1/9 (11.1%) | 1 |
| Haematocrit decreased | 1/141 (0.7%) | 1 | 2/180 (1.1%) | 2 | 0/42 (0%) | 0 | 1/9 (11.1%) | 1 |
| Haemoglobin decreased | 3/141 (2.1%) | 4 | 5/180 (2.8%) | 5 | 1/42 (2.4%) | 1 | 1/9 (11.1%) | 1 |
| Neutrophil count increased | 0/141 (0%) | 0 | 1/180 (0.6%) | 1 | 0/42 (0%) | 0 | 1/9 (11.1%) | 1 |
| Prostatic specific antigen increased | 4/141 (2.8%) | 4 | 2/180 (1.1%) | 2 | 1/42 (2.4%) | 1 | 1/9 (11.1%) | 1 |
| Red blood cell count increased | 0/141 (0%) | 0 | 0/180 (0%) | 0 | 0/42 (0%) | 0 | 1/9 (11.1%) | 1 |
| Weight decreased | 16/141 (11.3%) | 19 | 15/180 (8.3%) | 15 | 5/42 (11.9%) | 6 | 0/9 (0%) | 0 |
| White blood cell count increased | 0/141 (0%) | 0 | 0/180 (0%) | 0 | 0/42 (0%) | 0 | 1/9 (11.1%) | 1 |
| Metabolism and nutrition disorders | ||||||||
| Decreased appetite | 16/141 (11.3%) | 19 | 13/180 (7.2%) | 13 | 2/42 (4.8%) | 3 | 0/9 (0%) | 0 |
| Diabetes mellitus | 0/141 (0%) | 0 | 1/180 (0.6%) | 1 | 0/42 (0%) | 0 | 1/9 (11.1%) | 1 |
| Hypercholesterolaemia | 3/141 (2.1%) | 3 | 1/180 (0.6%) | 1 | 3/42 (7.1%) | 3 | 0/9 (0%) | 0 |
| Hyperglycaemia | 2/141 (1.4%) | 2 | 0/180 (0%) | 0 | 3/42 (7.1%) | 4 | 0/9 (0%) | 0 |
| Hyperkalaemia | 1/141 (0.7%) | 1 | 2/180 (1.1%) | 2 | 2/42 (4.8%) | 2 | 1/9 (11.1%) | 2 |
| Hypokalaemia | 2/141 (1.4%) | 2 | 3/180 (1.7%) | 3 | 1/42 (2.4%) | 1 | 1/9 (11.1%) | 1 |
| Musculoskeletal and connective tissue disorders | ||||||||
| Arthralgia | 16/141 (11.3%) | 22 | 27/180 (15%) | 39 | 9/42 (21.4%) | 11 | 5/9 (55.6%) | 6 |
| Back pain | 29/141 (20.6%) | 39 | 34/180 (18.9%) | 40 | 11/42 (26.2%) | 15 | 1/9 (11.1%) | 1 |
| Bone pain | 10/141 (7.1%) | 13 | 12/180 (6.7%) | 15 | 1/42 (2.4%) | 1 | 1/9 (11.1%) | 1 |
| Flank pain | 5/141 (3.5%) | 5 | 2/180 (1.1%) | 2 | 3/42 (7.1%) | 3 | 0/9 (0%) | 0 |
| Gouty arthritis | 0/141 (0%) | 0 | 0/180 (0%) | 0 | 0/42 (0%) | 0 | 1/9 (11.1%) | 1 |
| Musculoskeletal chest pain | 6/141 (4.3%) | 8 | 4/180 (2.2%) | 4 | 3/42 (7.1%) | 3 | 0/9 (0%) | 0 |
| Musculoskeletal pain | 8/141 (5.7%) | 9 | 17/180 (9.4%) | 23 | 5/42 (11.9%) | 5 | 1/9 (11.1%) | 1 |
| Myalgia | 9/141 (6.4%) | 10 | 5/180 (2.8%) | 5 | 1/42 (2.4%) | 2 | 0/9 (0%) | 0 |
| Neck pain | 2/141 (1.4%) | 3 | 2/180 (1.1%) | 2 | 4/42 (9.5%) | 4 | 1/9 (11.1%) | 1 |
| Osteoarthritis | 0/141 (0%) | 0 | 0/180 (0%) | 0 | 4/42 (9.5%) | 6 | 1/9 (11.1%) | 1 |
| Osteonecrosis of jaw | 0/141 (0%) | 0 | 0/180 (0%) | 0 | 1/42 (2.4%) | 1 | 1/9 (11.1%) | 1 |
| Pain in extremity | 16/141 (11.3%) | 22 | 9/180 (5%) | 12 | 5/42 (11.9%) | 8 | 1/9 (11.1%) | 1 |
| Nervous system disorders | ||||||||
| Amnesia | 4/141 (2.8%) | 5 | 0/180 (0%) | 0 | 2/42 (4.8%) | 2 | 1/9 (11.1%) | 1 |
| Dizziness | 12/141 (8.5%) | 15 | 15/180 (8.3%) | 16 | 6/42 (14.3%) | 6 | 2/9 (22.2%) | 2 |
| Headache | 11/141 (7.8%) | 14 | 6/180 (3.3%) | 6 | 8/42 (19%) | 10 | 3/9 (33.3%) | 4 |
| Lethargy | 5/141 (3.5%) | 6 | 4/180 (2.2%) | 4 | 3/42 (7.1%) | 3 | 1/9 (11.1%) | 1 |
| Parkinson's disease | 0/141 (0%) | 0 | 0/180 (0%) | 0 | 0/42 (0%) | 0 | 1/9 (11.1%) | 1 |
| Poor quality sleep | 0/141 (0%) | 0 | 2/180 (1.1%) | 2 | 0/42 (0%) | 0 | 1/9 (11.1%) | 2 |
| Syncope | 0/141 (0%) | 0 | 2/180 (1.1%) | 2 | 0/42 (0%) | 0 | 1/9 (11.1%) | 1 |
| Psychiatric disorders | ||||||||
| Depressed mood | 1/141 (0.7%) | 1 | 0/180 (0%) | 0 | 0/42 (0%) | 0 | 1/9 (11.1%) | 2 |
| Insomnia | 9/141 (6.4%) | 9 | 8/180 (4.4%) | 8 | 1/42 (2.4%) | 1 | 1/9 (11.1%) | 1 |
| Renal and urinary disorders | ||||||||
| Dysuria | 5/141 (3.5%) | 5 | 4/180 (2.2%) | 4 | 1/42 (2.4%) | 1 | 1/9 (11.1%) | 1 |
| Haematuria | 3/141 (2.1%) | 5 | 6/180 (3.3%) | 7 | 5/42 (11.9%) | 5 | 0/9 (0%) | 0 |
| Hypertonic bladder | 2/141 (1.4%) | 2 | 1/180 (0.6%) | 1 | 0/42 (0%) | 0 | 1/9 (11.1%) | 2 |
| Pollakiuria | 7/141 (5%) | 7 | 6/180 (3.3%) | 6 | 1/42 (2.4%) | 1 | 1/9 (11.1%) | 1 |
| Renal failure chronic | 2/141 (1.4%) | 2 | 0/180 (0%) | 0 | 0/42 (0%) | 0 | 1/9 (11.1%) | 1 |
| Renal pain | 0/141 (0%) | 0 | 0/180 (0%) | 0 | 3/42 (7.1%) | 3 | 0/9 (0%) | 0 |
| Urinary retention | 4/141 (2.8%) | 4 | 5/180 (2.8%) | 7 | 1/42 (2.4%) | 1 | 1/9 (11.1%) | 1 |
| Reproductive system and breast disorders | ||||||||
| Gynaecomastia | 4/141 (2.8%) | 4 | 2/180 (1.1%) | 2 | 6/42 (14.3%) | 6 | 0/9 (0%) | 0 |
| Testicular pain | 5/141 (3.5%) | 5 | 0/180 (0%) | 0 | 1/42 (2.4%) | 1 | 1/9 (11.1%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Bronchitis chronic | 0/141 (0%) | 0 | 0/180 (0%) | 0 | 0/42 (0%) | 0 | 1/9 (11.1%) | 1 |
| Chronic obstructive pulmonary disease | 1/141 (0.7%) | 1 | 1/180 (0.6%) | 1 | 1/42 (2.4%) | 1 | 1/9 (11.1%) | 1 |
| Cough | 5/141 (3.5%) | 6 | 8/180 (4.4%) | 8 | 2/42 (4.8%) | 2 | 1/9 (11.1%) | 1 |
| Dyspnoea | 7/141 (5%) | 8 | 9/180 (5%) | 10 | 4/42 (9.5%) | 8 | 0/9 (0%) | 0 |
| Nasal congestion | 2/141 (1.4%) | 3 | 1/180 (0.6%) | 1 | 1/42 (2.4%) | 1 | 1/9 (11.1%) | 2 |
| Skin and subcutaneous tissue disorders | ||||||||
| Skin lesion | 1/141 (0.7%) | 1 | 0/180 (0%) | 0 | 0/42 (0%) | 0 | 1/9 (11.1%) | 1 |
| Surgical and medical procedures | ||||||||
| Jaw operation | 0/141 (0%) | 0 | 0/180 (0%) | 0 | 0/42 (0%) | 0 | 1/9 (11.1%) | 1 |
| Vascular disorders | ||||||||
| Hot flush | 15/141 (10.6%) | 16 | 17/180 (9.4%) | 17 | 12/42 (28.6%) | 12 | 4/9 (44.4%) | 5 |
| Hypertension | 18/141 (12.8%) | 29 | 14/180 (7.8%) | 16 | 13/42 (31%) | 16 | 0/9 (0%) | 0 |
| Hypotension | 1/141 (0.7%) | 1 | 2/180 (1.1%) | 2 | 1/42 (2.4%) | 1 | 1/9 (11.1%) | 1 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Institute and/or Principal Investigator may publish trial data generated at their specific study site after Sponsor publication of the multi-center data. Sponsor must receive a site's manuscript prior to publication for review and comment as specified in the Investigator Agreement.
Results Point of Contact
| Name/Title | Executive Medical Director |
|---|---|
| Organization | Astellas Pharma Global Development, Inc. (APGD) |
| Phone | |
| Astellas.resultsdisclosure@astellas.com |
Responsible Party:
Astellas Pharma Inc
ClinicalTrials.gov Identifier:
NCT01288911
Other Study ID Numbers:
- 9785-CL-0222
- 2010-021868-15
First Posted:
Feb 3, 2011
Last Update Posted:
Jul 27, 2022
Last Verified:
Jul 1, 2022