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
Enrollment
88
Locations
2
Arms
79.6
Actual Duration (Months)
4.3
Patients Per Site
0.1
Patients Per Site Per Month

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 DiseaseIntervention/TreatmentPhase
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

ArmIntervention/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:
  • MDV3100
  • 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:
  • Casodex
  • Outcome Measures

    Primary Outcome Measures

    1. 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

    1. 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.

    2. 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.

    3. 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.

    4. 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.

    5. 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

    6. 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.

    7. 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.

    8. 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.

    9. 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.

    10. 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.

    11. 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:

    1. Condom (barrier method of contraception), AND

    2. 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

    SiteCityStateCountryPostal Code
    1Site US1934HomewoodAlabamaUnited States35209
    2Site US1527AnchorageAlaskaUnited States99503
    3Site US3026TucsonArizonaUnited States85715
    4Site US2977HighlandCaliforniaUnited States92346
    5Site US3630San DiegoCaliforniaUnited States92123
    6Site US2935DenverColoradoUnited States80211
    7Site US2945MiddleburyConnecticutUnited States06762
    8Site US2014Melrose ParkIllinoisUnited States60160
    9Site US2067SpringfieldIllinoisUnited States62703
    10Site US2027JeffersonvilleIndianaUnited States47130
    11Site US1838West Des MoinesIowaUnited States50266
    12Site US62Kansas CityKansasUnited States66160-7233
    13Site US2976BaltimoreMarylandUnited States21201
    14Site US3182BethesdaMarylandUnited States20889-5600
    15Site US2975Ann ArborMichiganUnited States48109
    16Site US892Grand RapidsMichiganUnited States49546
    17Site US20MinneapolisMinnesotaUnited States55455
    18Site US3078BillingsMontanaUnited States59101
    19Site US2968LawrencevilleNew JerseyUnited States08648
    20Site US3025PoughkeepsieNew YorkUnited States12601
    21Site US1675RochesterNew YorkUnited States14642
    22Site US2934Staten IslandNew YorkUnited States10304
    23Site US81Chapel HillNorth CarolinaUnited States27599
    24Site US2104GreensboroNorth CarolinaUnited States27403
    25Site US44CincinnatiOhioUnited States45267
    26Site US2185ColumbusOhioUnited States43221
    27Site US1598Bala-CynwydPennsylvaniaUnited States19004
    28Site US1680LancasterPennsylvaniaUnited States17604
    29Site US2926Myrtle BeachSouth CarolinaUnited States29572
    30Site US1657NashvilleTennesseeUnited States37209
    31Site US464HoustonTexasUnited States77030
    32Site US2978San AntonioTexasUnited States78229
    33Site US1653Virginia BeachVirginiaUnited States23462
    34Site US1580BurienWashingtonUnited States98166
    35Site US1709WenatcheeWashingtonUnited States98801
    36Site US51MilwaukeeWisconsinUnited States53226
    37Site BE3015BrusselsBelgium1090
    38Site BE1322GentBelgium9000
    39Site BE3018KortrijkBelgium8500
    40Site BE3288LeuvenBelgium3000
    41Site BE3289LiegeBelgium
    42Site BE3013TurnhoutBelgium2300
    43Site CA3104CalgaryAlbertaCanadaT2V 1P9
    44Site CA3242AbbotsfordBritish ColumbiaCanadaV2S 3N5
    45Site CA2646KingstonOntarioCanadaK7L 2V7
    46Site CA166TorontoOntarioCanadaM4N 3M5
    47Site CA3084TorontoOntarioCanadaM5G 2M9
    48Site CA2984GranbyQuebecCanadaJ2G 8Z9
    49Site CA170MontrealQuebecCanadaH3G 1A4
    50Site DK3354AalborgDenmark9000
    51Site DK3356AarhusDenmark8200
    52Site DK1857CopenhagenDenmark2200
    53Site DK1263HerlevDenmark2730
    54Site FR1091CreteilFrance94010
    55Site FR3009LilleFrance59037
    56Site FR442Lyon Cedex 3France69437
    57Site FR3002Paris Cedex 10France75020
    58Site FR3003Poitiers CedexFrance86000
    59Site FR3000Rennes CedexFrance35033
    60Site FR3007RouenFrance76031
    61Site FR3005Suresnes CedexFrance92151
    62Site DE4000NuertingenBaden-WuerttembergGermany72622
    63Site DE2989AachenGermany51074
    64Site DE3287Bergisch GladbachGermanyD-51465
    65Site DE2993BonnGermany53105
    66Site DE2995BonnGermany53111
    67Site DE2994BonnGermany53117
    68Site DE2990HamburgGermany22081
    69Site DE3270HannoverGermany30625
    70Site DE2992ReutlingenGermany72764
    71Site DE3286Waldshut-TiengenGermany29761
    72Site DE2988WuppertalGermany42103
    73Site RO3042BucharestRORomania022328
    74Site RO3039BucharestRORomania050659
    75Site RO3035BucharestRomania041345
    76Site GB3029BristolUKUnited KingdomBS2 8HW
    77Site GB3027LondonUKUnited KingdomSE19RT
    78Site GB3030LondonUKUnited KingdomSW17 0QT
    79Site GB3028CardiffWalesUnited KingdomCF14 4XW
    80Site GB3244BelfastUnited KingdomBT9 7AB
    81Site GB2702CambridgeUnited KingdomCB2 0QQ
    82Site GB3166GlasgowUnited KingdomG12 0YN
    83Site GB1862LeicherUnited KingdomLE5 4PW
    84Site GB3163LondonUnited KingdomNW1 2PG
    85Site GB2624ManchesterUnited KingdomM20 4BX
    86Site GB3355MerseysideUnited KingdomCH63 4JY
    87Site GB3245Northwood, MiddlesexUnited KingdomHA6 2RN
    88Site GB3290PrestonUnited KingdomPR2 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:
    Aug 14, 2019
    Last Verified:
    Jul 1, 2019
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    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 DetailsMen with metastatic castration-resistant prostate cancer (mCRPC) were enrolled at 84 sites in a total of 8 countries.
    Pre-assignment DetailParticipants 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 TitleEnzalutamideBicalutamide
    Arm/Group DescriptionParticipants 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
    STARTED184191
    Received Treatment183189
    COMPLETED429
    NOT COMPLETED142182
    Period Title: Double-blind Period
    STARTED429
    Received Treatment429
    COMPLETED00
    NOT COMPLETED429

    Baseline Characteristics

    Arm/Group TitleEnzalutamideBicalutamideTotal
    Arm/Group DescriptionParticipants 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 Participants184191375
    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

    1. Primary Outcome
    TitleProgression Free Survival (PFS) Based on Independent Central Review (ICR) Assessment
    DescriptionPFS 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 FrameFrom 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 TitleEnzalutamideBicalutamide
    Arm/Group DescriptionParticipants 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 Participants184191
    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
    Comments
    Statistical Test of Hypothesisp-Value<0.0001
    Comments
    MethodLog Rank
    Comments
    Method of EstimationEstimation ParameterHazard Ratio (HR)
    Estimated Value0.44
    Confidence Interval (2-Sided) 95%
    0.34 to 0.57
    Parameter Dispersion Type:
    Value:
    Estimation CommentsEstimated by use of Cox proportional hazards model.
    2. Secondary Outcome
    TitlePFS Based on Investigator Assessment
    DescriptionPFS 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 FrameFrom 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 TitleEnzalutamideBicalutamide
    Arm/Group DescriptionParticipants 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 Participants184191
    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
    Comments
    Statistical Test of Hypothesisp-Value<0.0001
    Comments
    MethodLog Rank
    Comments
    Method of EstimationEstimation ParameterHazard Ratio (HR)
    Estimated Value0.42
    Confidence Interval (2-Sided) 95%
    0.33 to 0.55
    Parameter Dispersion Type:
    Value:
    Estimation CommentsEstimated by use of Cox proportional hazards model.
    3. Secondary Outcome
    TitleProstate-specific Antigen (PSA) Response by Week 13
    DescriptionThe 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 FrameBaseline to Week 13

    Outcome Measure Data

    Analysis Population Description
    Full analysis set with available PSA data
    Arm/Group TitleEnzalutamideBicalutamide
    Arm/Group DescriptionParticipants 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 Participants171163
    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
    Comments
    Statistical Test of Hypothesisp-Value<0.0001
    Comments
    MethodWilcoxon rank sum test
    Comments
    4. Secondary Outcome
    TitleBest PSA Response
    DescriptionThe 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 FrameBaseline 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 TitleEnzalutamideBicalutamide
    Arm/Group DescriptionParticipants 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 Participants174168
    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
    Comments
    Statistical Test of Hypothesisp-Value<0.0001
    Comments
    MethodWilcoxon rank sum test
    Comments
    5. Secondary Outcome
    TitleTime to PSA Progression
    DescriptionTime 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 FrameFrom 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 TitleEnzalutamideBicalutamide
    Arm/Group DescriptionParticipants 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 Participants184191
    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
    Comments
    Statistical Test of Hypothesisp-Value<0.0001
    Comments
    MethodLog Rank
    Comments
    Method of EstimationEstimation ParameterHazard Ratio (HR)
    Estimated Value0.28
    Confidence Interval (2-Sided) 95%
    0.20 to 0.39
    Parameter Dispersion Type:
    Value:
    Estimation CommentsEstimated by use of Cox proportional hazards model.
    6. Secondary Outcome
    TitleTime to PSA ≤ 4 ng/mL
    DescriptionTime 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 FrameFrom 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 TitleEnzalutamideBicalutamide
    Arm/Group DescriptionParticipants 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 Participants184191
    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
    Comments
    Statistical Test of Hypothesisp-Value<0.0001
    Comments
    MethodLog Rank
    Comments
    Method of EstimationEstimation ParameterHazard Ratio (HR)
    Estimated Value5.07
    Confidence Interval (2-Sided) 95%
    3.18 to 8.09
    Parameter Dispersion Type:
    Value:
    Estimation CommentsEstimated by use of Cox proportional hazards model.
    7. Secondary Outcome
    TitleTime to ≥ 30% PSA Decline From Baseline
    DescriptionThe 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 FrameFrom 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 TitleEnzalutamideBicalutamide
    Arm/Group DescriptionParticipants 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 Participants184191
    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
    Comments
    Statistical Test of Hypothesisp-Value<0.0001
    Comments
    MethodLog Rank
    Comments
    Method of EstimationEstimation ParameterHazard Ratio (HR)
    Estimated Value5.55
    Confidence Interval (2-Sided) 95%
    3.96 to 7.79
    Parameter Dispersion Type:
    Value:
    Estimation CommentsEstimated by use of Cox proportional hazards model.
    8. Secondary Outcome
    TitleTime to ≥ 50% PSA Decline From Baseline
    DescriptionThe 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 FrameFrom 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 TitleEnzalutamideBicalutamide
    Arm/Group DescriptionParticipants 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 Participants184191
    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
    Comments
    Statistical Test of Hypothesisp-Value<0.0001
    Comments
    MethodLog Rank
    Comments
    Method of EstimationEstimation ParameterHazard Ratio (HR)
    Estimated Value7.01
    Confidence Interval (2-Sided) 95%
    4.83 to 10.16
    Parameter Dispersion Type:
    Value:
    Estimation CommentsEstimated by use of Cox proportional hazards model.
    9. Secondary Outcome
    TitleTime to ≥ 90% PSA Decline From Baseline
    DescriptionThe 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 FrameFrom 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 TitleEnzalutamideBicalutamide
    Arm/Group DescriptionParticipants 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 Participants184191
    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
    Comments
    Statistical Test of Hypothesisp-Value<0.0001
    Comments
    MethodLog Rank
    Comments
    Method of EstimationEstimation ParameterHazard Ratio (HR)
    Estimated Value13.91
    Confidence Interval (2-Sided) 95%
    7.23 to 26.79
    Parameter Dispersion Type:
    Value:
    Estimation CommentsEstimated by use of Cox proportional hazards model.
    10. Secondary Outcome
    TitleRadiographic PFS Based on ICR Assessment
    DescriptionRadiographic 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 FrameFrom 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 TitleEnzalutamideBicalutamide
    Arm/Group DescriptionParticipants 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 Participants184191
    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
    Comments
    Statistical Test of Hypothesisp-Value0.0002
    Comments
    MethodLog Rank
    Comments
    Method of EstimationEstimation ParameterHazard Ratio (HR)
    Estimated Value0.51
    Confidence Interval (2-Sided) 95%
    0.36 to 0.74
    Parameter Dispersion Type:
    Value:
    Estimation CommentsEstimated by use of Cox proportional hazards model.
    11. Secondary Outcome
    TitlePercentage of Participants With an Objective Response
    DescriptionResponse 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 FrameFrom 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 TitleEnzalutamideBicalutamide
    Arm/Group DescriptionParticipants 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 Participants184191
    Number [percentage of participants]
    15.8
    8.6%
    2.6
    1.4%
    12. Secondary Outcome
    TitlePercentage of Participants With Adverse Events
    DescriptionA 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 FrameFrom 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 TitleEnzalutamideBicalutamideTotal Enzalutamide
    Arm/Group DescriptionParticipants 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 Participants183189192
    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 FrameFrom 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 TitleDouble-blind Period: EnzalutamideDouble-blind Period: BicalutamideOpen-label Period: Enzalutamide/EnzalutamideOpen-label Period: Bicalutamide/Enzalutamide
    Arm/Group DescriptionParticipants 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: EnzalutamideDouble-blind Period: BicalutamideOpen-label Period: Enzalutamide/EnzalutamideOpen-label Period: Bicalutamide/Enzalutamide
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total11/141 (7.8%) 7/180 (3.9%) 0/42 (0%) 1/9 (11.1%)
    Serious Adverse Events
    Double-blind Period: EnzalutamideDouble-blind Period: BicalutamideOpen-label Period: Enzalutamide/EnzalutamideOpen-label Period: Bicalutamide/Enzalutamide
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total49/141 (34.8%) 43/180 (23.9%) 18/42 (42.9%) 4/9 (44.4%)
    Blood and lymphatic system disorders
    Anaemia5/141 (3.5%) 50/180 (0%) 01/42 (2.4%) 10/9 (0%) 0
    Febrile bone marrow aplasia0/141 (0%) 01/180 (0.6%) 10/42 (0%) 00/9 (0%) 0
    Pancytopenia1/141 (0.7%) 11/180 (0.6%) 10/42 (0%) 00/9 (0%) 0
    Cardiac disorders
    Acute myocardial infarction1/141 (0.7%) 10/180 (0%) 00/42 (0%) 00/9 (0%) 0
    Angina pectoris0/141 (0%) 00/180 (0%) 01/42 (2.4%) 10/9 (0%) 0
    Aortic valve stenosis0/141 (0%) 00/180 (0%) 01/42 (2.4%) 10/9 (0%) 0
    Arteriosclerosis coronary artery0/141 (0%) 00/180 (0%) 01/42 (2.4%) 10/9 (0%) 0
    Atrial fibrillation2/141 (1.4%) 21/180 (0.6%) 11/42 (2.4%) 10/9 (0%) 0
    Atrioventricular block0/141 (0%) 00/180 (0%) 00/42 (0%) 01/9 (11.1%) 1
    Atrioventricular block complete0/141 (0%) 00/180 (0%) 01/42 (2.4%) 10/9 (0%) 0
    Bradycardia0/141 (0%) 00/180 (0%) 01/42 (2.4%) 11/9 (11.1%) 1
    Cardiac failure congestive3/141 (2.1%) 33/180 (1.7%) 32/42 (4.8%) 20/9 (0%) 0
    Cardiogenic shock0/141 (0%) 00/180 (0%) 00/42 (0%) 01/9 (11.1%) 1
    Coronary artery disease0/141 (0%) 00/180 (0%) 01/42 (2.4%) 10/9 (0%) 0
    Mitral valve incompetence0/141 (0%) 01/180 (0.6%) 10/42 (0%) 00/9 (0%) 0
    Myocardial infarction4/141 (2.8%) 40/180 (0%) 00/42 (0%) 00/9 (0%) 0
    Sick sinus syndrome0/141 (0%) 01/180 (0.6%) 10/42 (0%) 00/9 (0%) 0
    Sinus tachycardia0/141 (0%) 00/180 (0%) 01/42 (2.4%) 10/9 (0%) 0
    Supraventricular tachycardia0/141 (0%) 01/180 (0.6%) 10/42 (0%) 00/9 (0%) 0
    Ventricular extrasystoles1/141 (0.7%) 10/180 (0%) 00/42 (0%) 00/9 (0%) 0
    Ventricular fibrillation0/141 (0%) 00/180 (0%) 00/42 (0%) 01/9 (11.1%) 1
    Ventricular tachyarrhythmia1/141 (0.7%) 10/180 (0%) 00/42 (0%) 00/9 (0%) 0
    Congenital, familial and genetic disorders
    Arteriovenous malformation1/141 (0.7%) 10/180 (0%) 00/42 (0%) 00/9 (0%) 0
    Gastrointestinal disorders
    Abdominal pain2/141 (1.4%) 22/180 (1.1%) 22/42 (4.8%) 20/9 (0%) 0
    Constipation2/141 (1.4%) 22/180 (1.1%) 20/42 (0%) 00/9 (0%) 0
    Diarrhoea0/141 (0%) 01/180 (0.6%) 10/42 (0%) 00/9 (0%) 0
    Diverticulum0/141 (0%) 01/180 (0.6%) 10/42 (0%) 00/9 (0%) 0
    Gastrointestinal haemorrhage0/141 (0%) 00/180 (0%) 01/42 (2.4%) 10/9 (0%) 0
    Haematemesis1/141 (0.7%) 10/180 (0%) 00/42 (0%) 00/9 (0%) 0
    Haematochezia1/141 (0.7%) 10/180 (0%) 00/42 (0%) 00/9 (0%) 0
    Lower gastrointestinal haemorrhage0/141 (0%) 00/180 (0%) 01/42 (2.4%) 10/9 (0%) 0
    Rectal haemorrhage1/141 (0.7%) 11/180 (0.6%) 10/42 (0%) 00/9 (0%) 0
    Salivary gland calculus0/141 (0%) 00/180 (0%) 01/42 (2.4%) 10/9 (0%) 0
    Vomiting0/141 (0%) 01/180 (0.6%) 10/42 (0%) 00/9 (0%) 0
    General disorders
    Asthenia1/141 (0.7%) 10/180 (0%) 00/42 (0%) 00/9 (0%) 0
    Fatigue1/141 (0.7%) 10/180 (0%) 00/42 (0%) 00/9 (0%) 0
    General physical health deterioration1/141 (0.7%) 10/180 (0%) 02/42 (4.8%) 20/9 (0%) 0
    Generalised oedema0/141 (0%) 01/180 (0.6%) 10/42 (0%) 00/9 (0%) 0
    Non-cardiac chest pain1/141 (0.7%) 10/180 (0%) 00/42 (0%) 00/9 (0%) 0
    Pain0/141 (0%) 01/180 (0.6%) 20/42 (0%) 00/9 (0%) 0
    Pyrexia0/141 (0%) 01/180 (0.6%) 10/42 (0%) 00/9 (0%) 0
    Systemic inflammatory response syndrome1/141 (0.7%) 10/180 (0%) 00/42 (0%) 00/9 (0%) 0
    Hepatobiliary disorders
    Cholelithiasis0/141 (0%) 00/180 (0%) 01/42 (2.4%) 10/9 (0%) 0
    Infections and infestations
    Abscess of salivary gland0/141 (0%) 00/180 (0%) 01/42 (2.4%) 10/9 (0%) 0
    Arthritis bacterial0/141 (0%) 01/180 (0.6%) 10/42 (0%) 00/9 (0%) 0
    Bacteraemia1/141 (0.7%) 10/180 (0%) 00/42 (0%) 01/9 (11.1%) 1
    Cellulitis1/141 (0.7%) 10/180 (0%) 00/42 (0%) 00/9 (0%) 0
    Cystitis1/141 (0.7%) 20/180 (0%) 00/42 (0%) 00/9 (0%) 0
    Diverticulitis1/141 (0.7%) 10/180 (0%) 00/42 (0%) 00/9 (0%) 0
    Gastroenteritis1/141 (0.7%) 10/180 (0%) 00/42 (0%) 00/9 (0%) 0
    Gastroenteritis viral0/141 (0%) 01/180 (0.6%) 10/42 (0%) 00/9 (0%) 0
    Infection0/141 (0%) 00/180 (0%) 00/42 (0%) 01/9 (11.1%) 1
    Infective exacerbation of chronic obstructive airways disease0/141 (0%) 01/180 (0.6%) 10/42 (0%) 00/9 (0%) 0
    Pneumonia1/141 (0.7%) 12/180 (1.1%) 21/42 (2.4%) 10/9 (0%) 0
    Urosepsis2/141 (1.4%) 20/180 (0%) 01/42 (2.4%) 10/9 (0%) 0
    Injury, poisoning and procedural complications
    Ankle fracture0/141 (0%) 01/180 (0.6%) 10/42 (0%) 00/9 (0%) 0
    Craniocerebral injury1/141 (0.7%) 10/180 (0%) 00/42 (0%) 00/9 (0%) 0
    Fall1/141 (0.7%) 10/180 (0%) 00/42 (0%) 01/9 (11.1%) 1
    Hip fracture1/141 (0.7%) 11/180 (0.6%) 10/42 (0%) 00/9 (0%) 0
    Rib fracture2/141 (1.4%) 20/180 (0%) 00/42 (0%) 00/9 (0%) 0
    Investigations
    Alanine aminotransferase increased0/141 (0%) 01/180 (0.6%) 11/42 (2.4%) 10/9 (0%) 0
    Arteriogram coronary1/141 (0.7%) 10/180 (0%) 00/42 (0%) 00/9 (0%) 0
    Aspartate aminotransferase increased0/141 (0%) 01/180 (0.6%) 10/42 (0%) 00/9 (0%) 0
    Blood creatinine increased1/141 (0.7%) 11/180 (0.6%) 10/42 (0%) 00/9 (0%) 0
    Eastern Cooperative Oncology Group performance status worsened0/141 (0%) 01/180 (0.6%) 10/42 (0%) 00/9 (0%) 0
    Gamma-glutamyltransferase increased1/141 (0.7%) 11/180 (0.6%) 10/42 (0%) 00/9 (0%) 0
    Liver function test abnormal0/141 (0%) 00/180 (0%) 02/42 (4.8%) 20/9 (0%) 0
    Metabolism and nutrition disorders
    Dehydration2/141 (1.4%) 21/180 (0.6%) 10/42 (0%) 00/9 (0%) 0
    Hyperkalaemia0/141 (0%) 02/180 (1.1%) 20/42 (0%) 00/9 (0%) 0
    Hyponatraemia0/141 (0%) 01/180 (0.6%) 10/42 (0%) 00/9 (0%) 0
    Musculoskeletal and connective tissue disorders
    Arthralgia0/141 (0%) 01/180 (0.6%) 10/42 (0%) 01/9 (11.1%) 1
    Back pain1/141 (0.7%) 20/180 (0%) 00/42 (0%) 00/9 (0%) 0
    Bone pain0/141 (0%) 01/180 (0.6%) 10/42 (0%) 00/9 (0%) 0
    Joint lock1/141 (0.7%) 10/180 (0%) 00/42 (0%) 00/9 (0%) 0
    Lumbar spinal stenosis0/141 (0%) 01/180 (0.6%) 10/42 (0%) 00/9 (0%) 0
    Muscular weakness1/141 (0.7%) 10/180 (0%) 00/42 (0%) 00/9 (0%) 0
    Musculoskeletal chest pain1/141 (0.7%) 10/180 (0%) 01/42 (2.4%) 10/9 (0%) 0
    Osteoarthritis1/141 (0.7%) 10/180 (0%) 00/42 (0%) 00/9 (0%) 0
    Pain in extremity0/141 (0%) 01/180 (0.6%) 10/42 (0%) 00/9 (0%) 0
    Pathological fracture5/141 (3.5%) 62/180 (1.1%) 20/42 (0%) 00/9 (0%) 0
    Spinal column stenosis0/141 (0%) 01/180 (0.6%) 10/42 (0%) 00/9 (0%) 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Adenocarcinoma of colon0/141 (0%) 00/180 (0%) 01/42 (2.4%) 10/9 (0%) 0
    Basal cell carcinoma1/141 (0.7%) 41/180 (0.6%) 10/42 (0%) 00/9 (0%) 0
    Basosquamous carcinoma of skin1/141 (0.7%) 10/180 (0%) 00/42 (0%) 00/9 (0%) 0
    Bladder cancer1/141 (0.7%) 10/180 (0%) 00/42 (0%) 00/9 (0%) 0
    Bowen's disease0/141 (0%) 01/180 (0.6%) 10/42 (0%) 00/9 (0%) 0
    Brain neoplasm malignant1/141 (0.7%) 10/180 (0%) 00/42 (0%) 00/9 (0%) 0
    Cancer pain1/141 (0.7%) 10/180 (0%) 00/42 (0%) 00/9 (0%) 0
    Chronic lymphocytic leukaemia0/141 (0%) 00/180 (0%) 01/42 (2.4%) 10/9 (0%) 0
    Colon cancer0/141 (0%) 01/180 (0.6%) 10/42 (0%) 00/9 (0%) 0
    Gastric cancer0/141 (0%) 01/180 (0.6%) 10/42 (0%) 00/9 (0%) 0
    Gastrointestinal tract adenoma0/141 (0%) 01/180 (0.6%) 10/42 (0%) 00/9 (0%) 0
    Lung adenocarcinoma1/141 (0.7%) 10/180 (0%) 00/42 (0%) 00/9 (0%) 0
    Lung neoplasm malignant1/141 (0.7%) 10/180 (0%) 00/42 (0%) 00/9 (0%) 0
    Malignant neoplasm of conjunctiva1/141 (0.7%) 10/180 (0%) 00/42 (0%) 00/9 (0%) 0
    Malignant neoplasm progression2/141 (1.4%) 21/180 (0.6%) 13/42 (7.1%) 30/9 (0%) 0
    Metastases to central nervous system0/141 (0%) 01/180 (0.6%) 10/42 (0%) 00/9 (0%) 0
    Metastases to lung1/141 (0.7%) 10/180 (0%) 00/42 (0%) 00/9 (0%) 0
    Metastases to spine0/141 (0%) 01/180 (0.6%) 10/42 (0%) 00/9 (0%) 0
    Metastatic pain1/141 (0.7%) 11/180 (0.6%) 10/42 (0%) 00/9 (0%) 0
    Myelodysplastic syndrome1/141 (0.7%) 10/180 (0%) 00/42 (0%) 00/9 (0%) 0
    Neuroendocrine carcinoma1/141 (0.7%) 10/180 (0%) 00/42 (0%) 00/9 (0%) 0
    Paraneoplastic syndrome1/141 (0.7%) 10/180 (0%) 00/42 (0%) 00/9 (0%) 0
    Penile cancer1/141 (0.7%) 10/180 (0%) 00/42 (0%) 00/9 (0%) 0
    Skin cancer1/141 (0.7%) 10/180 (0%) 00/42 (0%) 00/9 (0%) 0
    Squamous cell carcinoma0/141 (0%) 00/180 (0%) 01/42 (2.4%) 10/9 (0%) 0
    Squamous cell carcinoma of skin0/141 (0%) 00/180 (0%) 02/42 (4.8%) 30/9 (0%) 0
    Superficial spreading melanoma stage unspecified1/141 (0.7%) 10/180 (0%) 00/42 (0%) 00/9 (0%) 0
    Ureteric cancer0/141 (0%) 01/180 (0.6%) 10/42 (0%) 00/9 (0%) 0
    Nervous system disorders
    Convulsion2/141 (1.4%) 20/180 (0%) 00/42 (0%) 00/9 (0%) 0
    Epiduritis1/141 (0.7%) 10/180 (0%) 00/42 (0%) 00/9 (0%) 0
    Hypoglycaemic seizure0/141 (0%) 01/180 (0.6%) 10/42 (0%) 00/9 (0%) 0
    Incoherent0/141 (0%) 00/180 (0%) 00/42 (0%) 01/9 (11.1%) 1
    Lacunar infarction1/141 (0.7%) 10/180 (0%) 00/42 (0%) 00/9 (0%) 0
    Paraplegia1/141 (0.7%) 10/180 (0%) 00/42 (0%) 00/9 (0%) 0
    Presyncope0/141 (0%) 01/180 (0.6%) 10/42 (0%) 00/9 (0%) 0
    Spinal cord compression1/141 (0.7%) 11/180 (0.6%) 10/42 (0%) 00/9 (0%) 0
    Syncope0/141 (0%) 01/180 (0.6%) 10/42 (0%) 00/9 (0%) 0
    Transient ischaemic attack1/141 (0.7%) 10/180 (0%) 01/42 (2.4%) 21/9 (11.1%) 1
    Tremor0/141 (0%) 01/180 (0.6%) 10/42 (0%) 00/9 (0%) 0
    Renal and urinary disorders
    Acute prerenal failure1/141 (0.7%) 10/180 (0%) 00/42 (0%) 00/9 (0%) 0
    Bladder obstruction0/141 (0%) 01/180 (0.6%) 10/42 (0%) 00/9 (0%) 0
    Bladder outlet obstruction0/141 (0%) 01/180 (0.6%) 10/42 (0%) 00/9 (0%) 0
    Dysuria0/141 (0%) 01/180 (0.6%) 10/42 (0%) 00/9 (0%) 0
    Haematuria2/141 (1.4%) 21/180 (0.6%) 12/42 (4.8%) 40/9 (0%) 0
    Hydronephrosis0/141 (0%) 02/180 (1.1%) 20/42 (0%) 00/9 (0%) 0
    Obstructive uropathy1/141 (0.7%) 10/180 (0%) 00/42 (0%) 00/9 (0%) 0
    Postrenal failure0/141 (0%) 02/180 (1.1%) 20/42 (0%) 00/9 (0%) 0
    Renal colic1/141 (0.7%) 10/180 (0%) 00/42 (0%) 00/9 (0%) 0
    Renal failure0/141 (0%) 01/180 (0.6%) 10/42 (0%) 00/9 (0%) 0
    Renal failure acute2/141 (1.4%) 20/180 (0%) 00/42 (0%) 01/9 (11.1%) 1
    Renal impairment0/141 (0%) 00/180 (0%) 01/42 (2.4%) 10/9 (0%) 0
    Stress urinary incontinence1/141 (0.7%) 20/180 (0%) 00/42 (0%) 00/9 (0%) 0
    Ureteric dilatation0/141 (0%) 01/180 (0.6%) 10/42 (0%) 00/9 (0%) 0
    Urethral obstruction0/141 (0%) 01/180 (0.6%) 10/42 (0%) 00/9 (0%) 0
    Urinary retention0/141 (0%) 02/180 (1.1%) 22/42 (4.8%) 20/9 (0%) 0
    Urinary tract obstruction1/141 (0.7%) 10/180 (0%) 00/42 (0%) 00/9 (0%) 0
    Reproductive system and breast disorders
    Prostatic obstruction0/141 (0%) 00/180 (0%) 01/42 (2.4%) 10/9 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory distress syndrome0/141 (0%) 01/180 (0.6%) 10/42 (0%) 00/9 (0%) 0
    Acute respiratory failure1/141 (0.7%) 10/180 (0%) 00/42 (0%) 00/9 (0%) 0
    Dyspnoea2/141 (1.4%) 21/180 (0.6%) 11/42 (2.4%) 10/9 (0%) 0
    Hypoxia0/141 (0%) 01/180 (0.6%) 10/42 (0%) 00/9 (0%) 0
    Pleural effusion0/141 (0%) 01/180 (0.6%) 11/42 (2.4%) 10/9 (0%) 0
    Pleuritic pain0/141 (0%) 01/180 (0.6%) 10/42 (0%) 00/9 (0%) 0
    Pneumonia aspiration2/141 (1.4%) 21/180 (0.6%) 10/42 (0%) 00/9 (0%) 0
    Pneumothorax1/141 (0.7%) 10/180 (0%) 00/42 (0%) 00/9 (0%) 0
    Pulmonary fibrosis1/141 (0.7%) 10/180 (0%) 00/42 (0%) 00/9 (0%) 0
    Surgical and medical procedures
    Transurethral prostatectomy0/141 (0%) 00/180 (0%) 01/42 (2.4%) 10/9 (0%) 0
    Vascular disorders
    Aortic stenosis2/141 (1.4%) 20/180 (0%) 00/42 (0%) 00/9 (0%) 0
    Hypotension1/141 (0.7%) 10/180 (0%) 00/42 (0%) 00/9 (0%) 0
    Orthostatic hypotension1/141 (0.7%) 10/180 (0%) 00/42 (0%) 00/9 (0%) 0
    Peripheral artery stenosis0/141 (0%) 01/180 (0.6%) 10/42 (0%) 00/9 (0%) 0
    Venous thrombosis limb0/141 (0%) 01/180 (0.6%) 10/42 (0%) 00/9 (0%) 0
    Other (Not Including Serious) Adverse Events
    Double-blind Period: EnzalutamideDouble-blind Period: BicalutamideOpen-label Period: Enzalutamide/EnzalutamideOpen-label Period: Bicalutamide/Enzalutamide
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total123/141 (87.2%) 149/180 (82.8%) 42/42 (100%) 9/9 (100%)
    Blood and lymphatic system disorders
    Anaemia10/141 (7.1%) 105/180 (2.8%) 74/42 (9.5%) 41/9 (11.1%) 1
    Cardiac disorders
    Angina pectoris0/141 (0%) 00/180 (0%) 01/42 (2.4%) 11/9 (11.1%) 1
    Palpitations2/141 (1.4%) 21/180 (0.6%) 10/42 (0%) 01/9 (11.1%) 1
    Eye disorders
    Cataract0/141 (0%) 00/180 (0%) 00/42 (0%) 01/9 (11.1%) 1
    Glaucoma0/141 (0%) 00/180 (0%) 00/42 (0%) 01/9 (11.1%) 1
    Ocular hyperaemia0/141 (0%) 00/180 (0%) 00/42 (0%) 01/9 (11.1%) 1
    Gastrointestinal disorders
    Abdominal pain6/141 (4.3%) 67/180 (3.9%) 73/42 (7.1%) 41/9 (11.1%) 1
    Constipation19/141 (13.5%) 2124/180 (13.3%) 255/42 (11.9%) 70/9 (0%) 0
    Diarrhoea16/141 (11.3%) 1815/180 (8.3%) 185/42 (11.9%) 62/9 (22.2%) 2
    Dyspepsia5/141 (3.5%) 64/180 (2.2%) 41/42 (2.4%) 12/9 (22.2%) 2
    Haemorrhoids1/141 (0.7%) 11/180 (0.6%) 10/42 (0%) 01/9 (11.1%) 1
    Nausea18/141 (12.8%) 2233/180 (18.3%) 3610/42 (23.8%) 110/9 (0%) 0
    Rectal haemorrhage4/141 (2.8%) 41/180 (0.6%) 11/42 (2.4%) 11/9 (11.1%) 1
    Vomiting5/141 (3.5%) 59/180 (5%) 101/42 (2.4%) 10/9 (0%) 0
    General disorders
    Asthenia8/141 (5.7%) 107/180 (3.9%) 72/42 (4.8%) 20/9 (0%) 0
    Fatigue35/141 (24.8%) 4038/180 (21.1%) 4518/42 (42.9%) 243/9 (33.3%) 3
    Oedema peripheral10/141 (7.1%) 1013/180 (7.2%) 135/42 (11.9%) 50/9 (0%) 0
    Pain1/141 (0.7%) 18/180 (4.4%) 82/42 (4.8%) 21/9 (11.1%) 1
    Infections and infestations
    Bronchitis1/141 (0.7%) 12/180 (1.1%) 23/42 (7.1%) 40/9 (0%) 0
    Influenza3/141 (2.1%) 44/180 (2.2%) 41/42 (2.4%) 11/9 (11.1%) 1
    Nasopharyngitis11/141 (7.8%) 137/180 (3.9%) 87/42 (16.7%) 91/9 (11.1%) 1
    Osteomyelitis0/141 (0%) 00/180 (0%) 01/42 (2.4%) 11/9 (11.1%) 1
    Scrotal infection0/141 (0%) 00/180 (0%) 00/42 (0%) 01/9 (11.1%) 1
    Urinary tract infection7/141 (5%) 83/180 (1.7%) 34/42 (9.5%) 40/9 (0%) 0
    Injury, poisoning and procedural complications
    Arthropod bite0/141 (0%) 00/180 (0%) 03/42 (7.1%) 30/9 (0%) 0
    Fall9/141 (6.4%) 116/180 (3.3%) 74/42 (9.5%) 62/9 (22.2%) 2
    Rib fracture1/141 (0.7%) 10/180 (0%) 02/42 (4.8%) 21/9 (11.1%) 1
    Investigations
    Blood alkaline phosphatase increased3/141 (2.1%) 45/180 (2.8%) 60/42 (0%) 01/9 (11.1%) 1
    Blood urea increased0/141 (0%) 03/180 (1.7%) 31/42 (2.4%) 11/9 (11.1%) 1
    Haematocrit decreased1/141 (0.7%) 12/180 (1.1%) 20/42 (0%) 01/9 (11.1%) 1
    Haemoglobin decreased3/141 (2.1%) 45/180 (2.8%) 51/42 (2.4%) 11/9 (11.1%) 1
    Neutrophil count increased0/141 (0%) 01/180 (0.6%) 10/42 (0%) 01/9 (11.1%) 1
    Prostatic specific antigen increased4/141 (2.8%) 42/180 (1.1%) 21/42 (2.4%) 11/9 (11.1%) 1
    Red blood cell count increased0/141 (0%) 00/180 (0%) 00/42 (0%) 01/9 (11.1%) 1
    Weight decreased16/141 (11.3%) 1915/180 (8.3%) 155/42 (11.9%) 60/9 (0%) 0
    White blood cell count increased0/141 (0%) 00/180 (0%) 00/42 (0%) 01/9 (11.1%) 1
    Metabolism and nutrition disorders
    Decreased appetite16/141 (11.3%) 1913/180 (7.2%) 132/42 (4.8%) 30/9 (0%) 0
    Diabetes mellitus0/141 (0%) 01/180 (0.6%) 10/42 (0%) 01/9 (11.1%) 1
    Hypercholesterolaemia3/141 (2.1%) 31/180 (0.6%) 13/42 (7.1%) 30/9 (0%) 0
    Hyperglycaemia2/141 (1.4%) 20/180 (0%) 03/42 (7.1%) 40/9 (0%) 0
    Hyperkalaemia1/141 (0.7%) 12/180 (1.1%) 22/42 (4.8%) 21/9 (11.1%) 2
    Hypokalaemia2/141 (1.4%) 23/180 (1.7%) 31/42 (2.4%) 11/9 (11.1%) 1
    Musculoskeletal and connective tissue disorders
    Arthralgia16/141 (11.3%) 2227/180 (15%) 399/42 (21.4%) 115/9 (55.6%) 6
    Back pain29/141 (20.6%) 3934/180 (18.9%) 4011/42 (26.2%) 151/9 (11.1%) 1
    Bone pain10/141 (7.1%) 1312/180 (6.7%) 151/42 (2.4%) 11/9 (11.1%) 1
    Flank pain5/141 (3.5%) 52/180 (1.1%) 23/42 (7.1%) 30/9 (0%) 0
    Gouty arthritis0/141 (0%) 00/180 (0%) 00/42 (0%) 01/9 (11.1%) 1
    Musculoskeletal chest pain6/141 (4.3%) 84/180 (2.2%) 43/42 (7.1%) 30/9 (0%) 0
    Musculoskeletal pain8/141 (5.7%) 917/180 (9.4%) 235/42 (11.9%) 51/9 (11.1%) 1
    Myalgia9/141 (6.4%) 105/180 (2.8%) 51/42 (2.4%) 20/9 (0%) 0
    Neck pain2/141 (1.4%) 32/180 (1.1%) 24/42 (9.5%) 41/9 (11.1%) 1
    Osteoarthritis0/141 (0%) 00/180 (0%) 04/42 (9.5%) 61/9 (11.1%) 1
    Osteonecrosis of jaw0/141 (0%) 00/180 (0%) 01/42 (2.4%) 11/9 (11.1%) 1
    Pain in extremity16/141 (11.3%) 229/180 (5%) 125/42 (11.9%) 81/9 (11.1%) 1
    Nervous system disorders
    Amnesia4/141 (2.8%) 50/180 (0%) 02/42 (4.8%) 21/9 (11.1%) 1
    Dizziness12/141 (8.5%) 1515/180 (8.3%) 166/42 (14.3%) 62/9 (22.2%) 2
    Headache11/141 (7.8%) 146/180 (3.3%) 68/42 (19%) 103/9 (33.3%) 4
    Lethargy5/141 (3.5%) 64/180 (2.2%) 43/42 (7.1%) 31/9 (11.1%) 1
    Parkinson's disease0/141 (0%) 00/180 (0%) 00/42 (0%) 01/9 (11.1%) 1
    Poor quality sleep0/141 (0%) 02/180 (1.1%) 20/42 (0%) 01/9 (11.1%) 2
    Syncope0/141 (0%) 02/180 (1.1%) 20/42 (0%) 01/9 (11.1%) 1
    Psychiatric disorders
    Depressed mood1/141 (0.7%) 10/180 (0%) 00/42 (0%) 01/9 (11.1%) 2
    Insomnia9/141 (6.4%) 98/180 (4.4%) 81/42 (2.4%) 11/9 (11.1%) 1
    Renal and urinary disorders
    Dysuria5/141 (3.5%) 54/180 (2.2%) 41/42 (2.4%) 11/9 (11.1%) 1
    Haematuria3/141 (2.1%) 56/180 (3.3%) 75/42 (11.9%) 50/9 (0%) 0
    Hypertonic bladder2/141 (1.4%) 21/180 (0.6%) 10/42 (0%) 01/9 (11.1%) 2
    Pollakiuria7/141 (5%) 76/180 (3.3%) 61/42 (2.4%) 11/9 (11.1%) 1
    Renal failure chronic2/141 (1.4%) 20/180 (0%) 00/42 (0%) 01/9 (11.1%) 1
    Renal pain0/141 (0%) 00/180 (0%) 03/42 (7.1%) 30/9 (0%) 0
    Urinary retention4/141 (2.8%) 45/180 (2.8%) 71/42 (2.4%) 11/9 (11.1%) 1
    Reproductive system and breast disorders
    Gynaecomastia4/141 (2.8%) 42/180 (1.1%) 26/42 (14.3%) 60/9 (0%) 0
    Testicular pain5/141 (3.5%) 50/180 (0%) 01/42 (2.4%) 11/9 (11.1%) 1
    Respiratory, thoracic and mediastinal disorders
    Bronchitis chronic0/141 (0%) 00/180 (0%) 00/42 (0%) 01/9 (11.1%) 1
    Chronic obstructive pulmonary disease1/141 (0.7%) 11/180 (0.6%) 11/42 (2.4%) 11/9 (11.1%) 1
    Cough5/141 (3.5%) 68/180 (4.4%) 82/42 (4.8%) 21/9 (11.1%) 1
    Dyspnoea7/141 (5%) 89/180 (5%) 104/42 (9.5%) 80/9 (0%) 0
    Nasal congestion2/141 (1.4%) 31/180 (0.6%) 11/42 (2.4%) 11/9 (11.1%) 2
    Skin and subcutaneous tissue disorders
    Skin lesion1/141 (0.7%) 10/180 (0%) 00/42 (0%) 01/9 (11.1%) 1
    Surgical and medical procedures
    Jaw operation0/141 (0%) 00/180 (0%) 00/42 (0%) 01/9 (11.1%) 1
    Vascular disorders
    Hot flush15/141 (10.6%) 1617/180 (9.4%) 1712/42 (28.6%) 124/9 (44.4%) 5
    Hypertension18/141 (12.8%) 2914/180 (7.8%) 1613/42 (31%) 160/9 (0%) 0
    Hypotension1/141 (0.7%) 12/180 (1.1%) 21/42 (2.4%) 11/9 (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/TitleExecutive Medical Director
    OrganizationAstellas Pharma Global Development, Inc. (APGD)
    Phone
    EmailAstellas.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:
    Aug 14, 2019
    Last Verified:
    Jul 1, 2019