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STRIVE: Safety and Efficacy Study of Enzalutamide Versus Bicalutamide in Men With Prostate Cancer

Sponsor
Pfizer (Industry)
Overall Status
Completed
CT.gov ID
NCT01664923
Collaborator
Astellas Pharma Inc (Industry), Medivation LLC, a wholly owned subsidiary of Pfizer Inc. (Industry)
396
Enrollment
109
Locations
2
Arms
65
Actual Duration (Months)
3.6
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to determine the safety and efficacy of enzalutamide vs bicalutamide in asymptomatic or mildly symptomatic patients with prostate cancer who have disease progression despite primary androgen deprivation therapy.

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

This study is a multicenter phase 2, randomized, double-blind, efficacy and safety study of enzalutamide (160 mg/day) vs. bicalutamide (50 mg/day) in patients with recurrent prostate cancer who have serologic and/or radiographic disease progression despite primary androgen deprivation therapy.

Throughout the study, safety and tolerability will be assessed by the recording of adverse events, monitoring of vital signs, physical examinations, and safety laboratory evaluations.

Following study unblinding, study patients receiving enzalutamide or bicalutamide at the time of unblinding and qualifying patients randomized to bicalutamide who discontinued prior to unblinding will be offered the opportunity to receive open label enzalutamide treatment.

Study Design

Study Type:
Interventional
Actual Enrollment :
396 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
STRIVE: A MULTICENTER PHASE 2, RANDOMIZED, DOUBLE-BLIND, EFFICACY AND SAFETY STUDY OF ENZALUTAMIDE VS. BICALUTAMIDE IN MEN WITH PROSTATE CANCER WHO HAVE FAILED PRIMARY ANDROGEN DEPRIVATION THERAPY
Actual Study Start Date :
Aug 1, 2012
Actual Primary Completion Date :
Feb 1, 2015
Actual Study Completion Date :
Jan 1, 2018

Arms and Interventions

Arm Intervention/Treatment
Experimental: Enzalutamide

Enzalutamide 160 mg/day orally

Drug: Enzalutamide
160 mg, daily, by mouth.
Other Names:
  • MDV3100
  • Xtandi

    		•
    Active Comparator: Bicalutamide

    50 mg/day orally

    Drug: Bicalutamide
    50 mg, daily, by mouth
    Other Names:
  • Casodex

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Progression Free Survival (PFS) [From randomization until the data cut-off date of 09 February 2015, median duration of treatment was 14.7 months in the enzalutamide arm and 8.4 months in the bicalutamide arm.]

      PFS was defined as time from randomization to earliest objective evidence of prostate specific-antigen (PSA) progression, radiographic progression, or death on study. PSA progression was defined as ≥ 25% increase in PSA with an absolute increase ≥ 2 ng/mL above the nadir and was to be confirmed by a second consecutive assessment. Radiographic progression in bone was based on The Prostate Cancer Clinical Trials Working Group (PCWG2) guidelines defined as at least 2 new lesions on bone scan. Radiographic progression in soft tissue on Computerized Tomography/Magnetic Resonance Imaging (CT/MRI) was based on Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). CT/MRI and bone scans were read locally by the same radiologist (or nuclear medicine physician for interpretation of bone scans) whenever possible. Participants not known to have had a PFS event at the time of the analysis data cutoff were censored at the date of last assessment.

    Secondary Outcome Measures

    1. Time to PSA Progression [From randomization until the data cut-off date of 09 February 2015, median duration of treatment was 14.7 months in the enzalutamide arm and 8.4 months in the bicalutamide arm.]

      PSA progression was defined as ≥ 25% increase in PSA with an absolute increase ≥ 2 ng/mL above the nadir and was to be confirmed by a second consecutive assessment at least 3 weeks later. Participants not known to have had PSA progression were censored at the date of last PSA assessment.

    2. Percentage of Participants With a PSA Response ≥ 50% [From randomization until the data cut-off date of 09 February 2015, median duration of treatment was 14.7 months in the enzalutamide arm and 8.4 months in the bicalutamide arm.]

      PSA response was defined as a reduction in PSA of at least 50% from baseline at any post baseline assessment confirmed by a second PSA assessment at least 3 weeks later.

    3. Duration of Radiographic PFS [From randomization until the data cut-off date of 09 February 2015, median duration of treatment was 14.7 months in the enzalutamide arm and 8.4 months in the bicalutamide arm.]

      Duration of radiographic PFS was defined as the time from randomization to the earliest objective evidence of radiographic disease progression or death on study and was to be evaluated for participants with metastatic disease at study entry. Radiographic disease progression in bone was based on PCWG2 guidelines defined as at least 2 new lesions on bone scan. Radiographic disease progression in soft tissue on CT/MRI was based on RECIST 1.1. CT/MRI and bone scans were read locally by the same radiologist (or nuclear medicine physician for interpretation of bone scans) whenever possible. Participants not known to have had radiographic progression at the time of analysis data cutoff were censored at the date of last radiographic assessment.

    4. Quality of Life: Time to Degradation of Functional Assessment of Cancer Therapy - Prostate (FACT-P) [From randomization until the data cut-off date of 09 February 2015, median duration of treatment was 14.7 months in the enzalutamide arm and 8.4 months in the bicalutamide arm.]

      The FACT-P is a multidimensional, self-reported quality of life instrument consisting of 27 core items that assess patient function in 4 domains: physical, social/family, emotional, and functional well-being, and supplemented by 12 site-specific items to assess for prostate-related symptoms. Each item is rated on a 0 to 4 Likert-type scale, and then combined to produce subscale scores for each domain, as well as a global quality of life score (0 to 156) with higher scores representing better quality of life. Time to degradation of FACT-P was defined as the time from randomization to first assessment with at least a 10-point decrease from baseline in the global FACT-P score for each participant. Participants with no score degradation at the time of analysis data cutoff were censored at the date of last assessment showing no degradation.

    5. Best Overall Soft Tissue Response [From randomization until the data cut-off date of 09 February 2015, median duration of treatment was 14.7 months in the enzalutamide arm and 8.4 months in the bicalutamide arm.]

      Best overall soft tissue response is defined as partial response (PR) or complete response (CR) while on study treatment based on investigator assessment of target, nontarget, and new lesions using RECIST 1.1. Only participants in the metastatic population with measurable soft tissue disease (at least 1 target lesion identified per RECIST 1.1) at screening were included in the analysis. All percentages are based on number of participants with metastatic and measurable soft tissue disease at screening in each treatment group.

    6. Percentage of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [From first dose of study drug until the end of open label phase (up to maximum duration of 65 months)]

      An AE was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. An SAE was an AE resulting in any of following outcomes or deemed significant for any other reason: death, initial or prolonged inpatient hospitalization, life-threatening experience (immediate risk of dying), persistent or significant disability or incapacity, congenital anomaly. A treatment emergent AE defined as an event that emerged during treatment period (From first dose of study drug until end of open label phase [up to maximum duration of 65 months]) that was absent before treatment, or worsened during treatment period relative to pre-treatment state. AE included both serious and non- SAE. Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. An AE was considered related to study drug if event was assessed by investigator as probably or possibly related.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    Male
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Males age 18 or older;

    • Histologically or cytologically confirmed adenocarcinoma of the prostate;

    • Ongoing androgen deprivation therapy;

    • Serum testosterone level ≤ 50 ng/dL (1.73 nmol/L) at the Screening visit;

    • Progressive disease at study entry defined by prostate-specific antigen (PSA) progression and/or radiographic progression that occurred while the patient was on primary androgen deprivation therapy;

    • Asymptomatic or mildly symptomatic from prostate cancer;

    • Eastern Cooperative Oncology Group (ECOG) performance status of 0-1;

    • Estimated life expectancy of ≥ 12 months;

    • Able to swallow the study drug and comply with study requirements.

    Exclusion Criteria:

    • Severe concurrent disease, infection, or co-morbidity;

    • Known or suspected brain metastasis or active leptomeningeal disease;

    • History of another invasive malignancy within the previous 5 years other than treated non-melanomatous skin cancer and American Joint Committee on Cancer (AJCC) Stage 0 or Stage 1 cancers that have a remote probability of recurrence;

    • Absolute neutrophil count < 1,500/µL, or platelet count < 100,000/µL, or hemoglobin < 9 g/dL at the Screening visit;

    • Total bilirubin, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2.5 times the upper limit of normal (ULN) at the Screening visit;

    • Creatinine > 2 mg/dL at the Screening visit;

    • Albumin < 3.0 g/dL at the Screening visit;

    • History of seizure or any condition that may predispose to seizure;

    • Clinically significant cardiovascular disease;

    • Gastrointestinal disorder affecting absorption (e.g., gastrectomy, active peptic ulcer disease within last 3 months);

    • Major surgery within 4 weeks of enrollment;

    • Use of opiate analgesics for pain from prostate cancer within 4 weeks of enrollment;

    • Radiation therapy for treatment of the primary tumor within 3 weeks of enrollment;

    • Prior radiation or radionuclide therapy for treatment of distant metastases;

    • Prior ketoconazole, abiraterone, or cytotoxic chemotherapy for prostate cancer;

    • Treatment with hormonal therapy or biologic therapy for prostate cancer within 4 weeks of enrollment;

    • Use of antiandrogens within 4 weeks prior to enrollment;

    • Prior disease progression, as assessed by the Investigator, while receiving bicalutamide;

    • Participation in a previous clinical trial of enzalutamide or an investigational agent that inhibits the androgen receptor or androgen synthesis (patients who received placebo are acceptable);

    • Use of an investigational agent within 4 weeks of enrollment;

    • Use of herbal products that may have hormonal anti-prostate cancer activity and/or are known to decrease PSA levels (e.g., saw palmetto) or systemic corticosteroids for prostate cancer within 4 weeks of enrollment;

    • Any condition or reason that, in the opinion of the Investigator, interferes with the ability of the patient to participate in the trial, which places the patient at undue risk, or complicates the interpretation of safety data.

    Open-Label Treatment Period:
    Inclusion Criteria:

    • Received randomized double blind treatment in MDV3100-09 as follows:

    • Randomized to enzalutamide and receiving enzalutamide at the time of study unblinding;

    • Randomized to bicalutamide and receiving bicalutamide at the time of study unblinding;

    • Randomized to bicalutamide and discontinued bicalutamide before study unblinding;

    • Willing to maintain androgen deprivation therapy with a gonadotropin releasing hormone (GnRH) agonist/antagonist or has had a bilateral orchiectomy.

    Exclusion Criteria:

    • Is currently or has taken commercially available enzalutamide (Xtandi) prior to participation in this open-label extension;

    • Discontinued enzalutamide during the double-blind portion of the study prior to unblinding;

    • Has any clinically significant cardiovascular, dermatologic, endocrine, gastrointestinal, hematologic, hepatic, infectious, metabolic, neurologic, psychiatric, psychologic, pulmonary, or renal disorder or any other condition, including excessive alcohol or drug abuse, or secondary malignancy, that may interfere with study participation in the opinion of the investigator or medical monitor;

    • Has a current or previously treated brain metastasis or leptomeningeal disease;

    • Has a history of seizure or any condition that may predispose to seizure (eg, prior cortical stroke or significant brain trauma);

    • Has a history of loss of consciousness or transient ischemic attack within 12 months of open label day 1;

    • Has taken cytotoxic chemotherapy or investigational therapy within 4 weeks before enrollment (open label day 1).

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of Alabama at Birmingham Birmingham Alabama United States 35233
    2 University of Alabama at Birmingham，IDS Pharmacy Birmingham Alabama United States 35249
    3 University of Alabama at Birmingham Birmingham Alabama United States 35294
    4 Desert Springs Cancer Care Scottsdale Arizona United States 85255
    5 Arizona Oncology Associates, PC - HOPE Tucson Arizona United States 85704
    6 Arizona Oncology Associates, PC - HOPE Tucson Arizona United States 85710
    7 Urological Associates of Southern Arizona, PC Tucson Arizona United States 85715
    8 Urological Associates of Southern Arizona, PC Tucson Arizona United States 85741
    9 Southern California Permanente Medical Group Anaheim California United States 92806
    10 Kaiser Permanente Medical Center Lab Drawing Station Antioch California United States 94509
    11 Kaiser Permanente Medical Center Lab Drawing Station Antioch California United States 94531
    12 Kaiser Permanente Medical Center Lab Drawing Station Fairfield California United States 94533-6901
    13 Kaiser Permanente Medical Center Lab Drawing Station Gilroy California United States 95020
    14 Southern California Permanente Medical Group Los Angeles California United States 90027
    15 Tower Urology Los Angeles California United States 90048
    16 UCLA Clark Urology Clinic Los Angeles California United States 90095
    17 UCLA Department of Pharmaceutical Services Los Angeles California United States 90095
    18 Kaiser Permanente Medical Center Lab Drawing Station Martinez California United States 94553
    19 Kaiser Permanente Medical Center Lab Drawing Station Milpitas California United States 95035-5491
    20 Kaiser Permanente Medical Center Lab Drawing Station Modesto California United States 95356
    21 Kaiser Permanente Medical Center Lab Drawing Station Moutain View California United States 94041
    22 Kaiser Permanente Medical Center Lab Drawing Station Napa California United States 94558-3313
    23 Kaiser Permanente Medical Center Oakland California United States 94611
    24 Kaiser Permanente Medical Center Lab Drawing Station Pleasanton California United States 94558
    25 Kaiser Permanente Medical Center Lab Drawing Station Redwood City California United States 94063
    26 Kaiser Permanente Medical Center Roseville California United States 95661
    27 UC Davis Comprehensive Cancer Center Sacramento California United States 95817
    28 UC Davis Medical Center Sacramento California United States 95817
    29 Kaiser Permanente Medical Center Sacramento California United States 95825
    30 San Bernardino Urological Associates Medical Group San Bernardino California United States 92404
    31 Southern California Permanente Medical Group San Diego California United States 92120
    32 Kaiser Permanente Medical Center San Francisco California United States 94115
    33 Kaiser Permanente Medical Center San Jose California United States 95119
    34 Kaiser Permanente Medical Center San Leandro California United States 94577
    35 Southern California Permanente Medical Group San Marcos California United States 92078
    36 Kaiser Permanente Medical Center Santa Clara California United States 95051
    37 Skyline Urology Sherman Oaks California United States 91411
    38 Kaiser Permanente Medical Center South San Francisco California United States 94080
    39 Standford Health Care Stanford California United States 94305
    40 Skyline Urology Torrance California United States 90505
    41 Kaiser Permanente Medical Center Vallejo California United States 94589
    42 Kaiser Permanente Medical Center Walnut Creek California United States 94596
    43 Anschutz Cancer Center Pavilion Pharmacy Aurora Colorado United States 80045
    44 Anschutz Inpatient Pavilion Aurora Colorado United States 80045
    45 University of Colorado Cancer Center, Anschutz Cancer Pavilion Aurora Colorado United States 80045
    46 The Urology Center of Colorado Denver Colorado United States 80211
    47 George Washington University - Medical Faculty Associates Washington District of Columbia United States 20037
    48 Advanced Urology institute Daytona Beach Florida United States 32114
    49 East Coast Institute for Research, LLC Jacksonville Florida United States 32207
    50 East Coast Institute for Research, LLC Jacksonville Florida United States 32216
    51 Specialists In Urology Naples Florida United States 34102
    52 First Urology, PSC Jeffersonville Indiana United States 47130
    53 Metairie Oncologist, LLC Metairie Louisiana United States 70006
    54 Ochsner Clinic Foundation New Orleans Louisiana United States 70121
    55 Regional Urology, LLC Shreveport Louisiana United States 71106
    56 Chesapeake Urology Research Associates Towson Maryland United States 21204
    57 Michigan Institute of Urology Troy Michigan United States 48084
    58 Minnesota Oncology Hematology, P.A. Edina Minnesota United States 55435-2150
    59 Minnesota Oncology Hematology, P.A. Woodbury Minnesota United States 55125
    60 Barnes-Jewish West County Hospital Creve Coeur Missouri United States 63141
    61 Barnes-Jewish Hospital Saint Louis Missouri United States 63110
    62 Washington University Infusion Center Pharmacy Saint Louis Missouri United States 63110
    63 Washington University, School of Medicine, 7th Floor, Center for Advanced Medicine Saint Louis Missouri United States 63110
    64 Siteman Cancer Center - South County Saint Louis Missouri United States 63129
    65 GU Research network,LLC / Urology Cancer Center Omaha Nebraska United States 68130
    66 Hackensack University Medical Center Hackensack New Jersey United States 07601
    67 John Theurer Cancer Center at Hackensack University Medical Center Hackensack New Jersey United States 07601
    68 AccuMed Research Associates Garden City New York United States 11530
    69 Premier Medical Group of the Hudson Valley PC Poughkeepsie New York United States 12601
    70 Associated Medical Professionals of NY, PLLC Syracuse New York United States 13210
    71 Carolinas Medical Center-Steelcreek Charlotte North Carolina United States 28278
    72 Carolina Clinical Trials, LLC Concord North Carolina United States 28025
    73 Carolina Urology Partners, PLLC Concord North Carolina United States 28025
    74 Duke University Medical Center Durham North Carolina United States 27710
    75 Investigational Chemotherapy Services Durham North Carolina United States 27710
    76 Alliance Urology Specialists, PA Greensboro North Carolina United States 27403
    77 Rowan Regional Medical Center Salisbury North Carolina United States 28144
    78 Wake Forest Baptist Health Urology Winston-Salem North Carolina United States 27103
    79 Wake Forest Baptist Health Winston-Salem North Carolina United States 27157
    80 TriState Urologic Services PSC Inc., dba The Urology Group Cincinnati Ohio United States 45212
    81 Cleveland Clinic Taussig Cancer Institute Cleveland Ohio United States 44195
    82 Peace Harbor Hospital Florence Oregon United States 97439
    83 Salem Hospital Salem Oregon United States 97301
    84 Oregon Urology Institute Springfield Oregon United States 97477
    85 Sacred Heart Nuclear Medicine Springfield Oregon United States 97477
    86 Lancaster Urology Lancaster Pennsylvania United States 17604
    87 Jefferson Medical Oncology Philadelphia Pennsylvania United States 19107
    88 Jefferson Urology Associates Philadelphia Pennsylvania United States 19107
    89 Thomas Jefferson University Hospital Philadelphia Pennsylvania United States 19107
    90 UPMC Cancer Center Hillman Cancer Center Pittsburgh Pennsylvania United States 15232
    91 Mount Nittany Physician Group State College Pennsylvania United States 16801
    92 Mount Nittany Health State College Pennsylvania United States 16803
    93 Charleston Hematology Oncology Associates, PA Charleston South Carolina United States 29414
    94 Carolina Urologic Research Center Myrtle Beach South Carolina United States 29572
    95 Urology Associates P.C. Nashville Tennessee United States 37209
    96 Vanderbilt University Medical Center Nashville Tennessee United States 37232
    97 Urology Clinics of North Texas Dallas Texas United States 75231
    98 Texas Oncology - Baylor Charles A. Sammons Cancer Center Dallas Texas United States 75246
    99 Texas Oncology-Memorial City Houston Texas United States 77024
    100 Urology San Antonio Research San Antonio Texas United States 78229
    101 University of Utah/Huntsman Cancer Hospital Salt Lake City Utah United States 84112
    102 University of Utah/Huntsman Cancer Institute Salt Lake City Utah United States 84112
    103 Virginia Oncology Associates Hampton Virginia United States 23666
    104 Virginia Oncology Associates Norfolk Virginia United States 23502
    105 Urology of Virginia, PLLC. Virginia Beach Virginia United States 23462
    106 Virginia Mason Medical Center Seattle Washington United States 98101
    107 Seattle Cancer Care Alliance Seattle Washington United States 98109
    108 University of Washington Medical Center Seattle Washington United States 98195
    109 University of Wisconsin Clinical Sciences Center Madison Wisconsin United States 53792

    Sponsors and Collaborators

    • Pfizer
    • Astellas Pharma Inc
    • Medivation LLC, a wholly owned subsidiary of Pfizer Inc.

    Investigators

    • Study Director: Pfizer Pfizer CT.gov Call Center, Pfizer

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Pfizer
    ClinicalTrials.gov Identifier:
    NCT01664923
    Other Study ID Numbers:
    • MDV3100-09
    • C3431014
    First Posted:
    Aug 14, 2012
    Last Update Posted:
    Jan 30, 2019
    Last Verified:
    Jan 1, 2019
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Keywords provided by Pfizer
    prostate cancer
    enzalutamide
    MDV3100
    Additional relevant MeSH terms:
    Prostatic Neoplasms
    Bicalutamide

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Enzalutamide Bicalutamide Then Enzalutamide
    Arm/Group Description Participants received enzalutamide 160 milligram (mg), self-administered as four 40-mg capsules, and 1 bicalutamide matching placebo capsule once per day, by mouth for up to 29 months in double blind (DB) phase. Participants who completed DB phase and consented to participate in open label phase, received enzalutamide 160 mg, self-administered as four 40-mg capsules once per day by mouth for up to 36 months in open label phase. Participants received bicalutamide 50 mg, self-administered as 1 capsule, once per day by mouth and 4 enzalutamide matching placebo capsules for up to 29 months in DB phase. Participants who completed DB phase and consented to participate in open label phase, received enzalutamide 160 mg, self-administered as four 40-mg capsules, once per day by mouth for up to 36 months in open label phase.
    Period Title: Period1:Double Blind Phase-29 Months
    STARTED 198 198
    Received Study Treatment 197 198
    COMPLETED 93 38
    NOT COMPLETED 105 160
    Period Title: Period1:Double Blind Phase-29 Months
    STARTED 93 38
    Treated 93 37
    COMPLETED 52 15
    NOT COMPLETED 41 23

    Baseline Characteristics

    Arm/Group Title Enzalutamide Bicalutamide Total
    Arm/Group Description Participants received enzalutamide 160 mg, self-administered as four 40-mg capsules, once per day by mouth and 1 bicalutamide-placebo capsule in DB phase. Participants received bicalutamide 50 mg, self-administered as 1 capsule, once per day by mouth and 4 enzalutamide-placebo capsules in DB phase. Total of all reporting groups
    Overall Participants 198 198 396
    Age, Customized (Count of Participants)
    < 65 years
    39
    19.7%
    25
    12.6%
    64
    16.2%
    65-74 years
    82
    41.4%
    76
    38.4%
    158
    39.9%
    ≥ 75 years
    77
    38.9%
    97
    49%
    174
    43.9%
    Sex/Gender, Customized (Count of Participants)
    Male
    198
    100%
    198
    100%
    396
    100%
    Region of Enrollment (Count of Participants)
    United States
    198
    100%
    198
    100%
    396
    100%

    Outcome Measures

    1. Primary Outcome
    Title Progression Free Survival (PFS)
    Description PFS was defined as time from randomization to earliest objective evidence of prostate specific-antigen (PSA) progression, radiographic progression, or death on study. PSA progression was defined as ≥ 25% increase in PSA with an absolute increase ≥ 2 ng/mL above the nadir and was to be confirmed by a second consecutive assessment. Radiographic progression in bone was based on The Prostate Cancer Clinical Trials Working Group (PCWG2) guidelines defined as at least 2 new lesions on bone scan. Radiographic progression in soft tissue on Computerized Tomography/Magnetic Resonance Imaging (CT/MRI) was based on Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). CT/MRI and bone scans were read locally by the same radiologist (or nuclear medicine physician for interpretation of bone scans) whenever possible. Participants not known to have had a PFS event at the time of the analysis data cutoff were censored at the date of last assessment.
    Time Frame From randomization until the data cut-off date of 09 February 2015, median duration of treatment was 14.7 months in the enzalutamide arm and 8.4 months in the bicalutamide arm.

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat population: all participants randomly assigned to study treatment.
    Arm/Group Title Enzalutamide Bicalutamide
    Arm/Group Description Participants received enzalutamide 160 mg, self-administered as four 40-mg capsules, once per day by mouth and 1 bicalutamide-placebo capsule in DB phase. Participants received bicalutamide 50 mg, self-administered as 1 capsule, once per day by mouth and 4 enzalutamide-placebo capsules in DB phase.
    Measure Participants 198 198
    Median (95% Confidence Interval) [months]
    19.4
    5.7
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Enzalutamide, Bicalutamide
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments P-value based on log-rank test stratified by disease stage at study entry as reported on the case report form (CRF).
    Method Log Rank
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.240
    Confidence Interval (2-Sided) 95%
    0.181 to 0.320
    Parameter Dispersion Type:
    Value:
    Estimation Comments Hazard ratio is based on a Cox regression model (with treatment as the only covariate) stratified by disease stage at study entry and is relative to bicalutamide with < 1 favoring enzalutamide.
    2. Secondary Outcome
    Title Time to PSA Progression
    Description PSA progression was defined as ≥ 25% increase in PSA with an absolute increase ≥ 2 ng/mL above the nadir and was to be confirmed by a second consecutive assessment at least 3 weeks later. Participants not known to have had PSA progression were censored at the date of last PSA assessment.
    Time Frame From randomization until the data cut-off date of 09 February 2015, median duration of treatment was 14.7 months in the enzalutamide arm and 8.4 months in the bicalutamide arm.

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat population: all participants randomly assigned to study treatment.
    Arm/Group Title Enzalutamide Bicalutamide
    Arm/Group Description Participants received enzalutamide 160 mg, self-administered as four 40-mg capsules, once per day by mouth and 1 bicalutamide-placebo capsule in DB phase. Participants received bicalutamide 50 mg, self-administered as 1 capsule, once per day by mouth and 4 enzalutamide-placebo capsules in DB phase.
    Measure Participants 198 198
    Median (95% Confidence Interval) [months]
    NA
    8.3
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Enzalutamide, Bicalutamide
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments P-value based on log-rank test stratified by disease stage at study entry as reported on the CRF.
    Method Log Rank
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.190
    Confidence Interval (2-Sided) 95%
    0.137 to 0.264
    Parameter Dispersion Type:
    Value:
    Estimation Comments Hazard ratio is based on a Cox regression model (with treatment as the only covariate) stratified by disease stage at study entry and is relative to bicalutamide with < 1 favoring enzalutamide.
    3. Secondary Outcome
    Title Percentage of Participants With a PSA Response ≥ 50%
    Description PSA response was defined as a reduction in PSA of at least 50% from baseline at any post baseline assessment confirmed by a second PSA assessment at least 3 weeks later.
    Time Frame From randomization until the data cut-off date of 09 February 2015, median duration of treatment was 14.7 months in the enzalutamide arm and 8.4 months in the bicalutamide arm.

    Outcome Measure Data

    Analysis Population Description
    Evaluable intent-to-treat population: all participants randomly assigned to study treatment and had a baseline and at least 1 post baseline PSA measurement.
    Arm/Group Title Enzalutamide Bicalutamide
    Arm/Group Description Participants received enzalutamide 160 mg, self-administered as four 40-mg capsules, once per day by mouth and 1 bicalutamide-placebo capsule in DB phase. Participants received bicalutamide 50 mg, self-administered as 1 capsule, once per day by mouth and 4 enzalutamide-placebo capsules in DB phase.
    Measure Participants 192 195
    Number (95% Confidence Interval) [percentage of participants]
    81.3
    41.1%
    31.3
    15.8%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Enzalutamide, Bicalutamide
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method Cochran-Mantel-Haenszel
    Comments Comparison of the 2 treatment groups using the Cochran-Mantel-Haenszel mean score test stratified by disease stage at study entry.
    Method of Estimation Estimation Parameter Difference in rates
    Estimated Value 50.0
    Confidence Interval (2-Sided) 95%
    41.4 to 58.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments Enzalutamide response rate minus bicalutamide response rate.
    4. Secondary Outcome
    Title Duration of Radiographic PFS
    Description Duration of radiographic PFS was defined as the time from randomization to the earliest objective evidence of radiographic disease progression or death on study and was to be evaluated for participants with metastatic disease at study entry. Radiographic disease progression in bone was based on PCWG2 guidelines defined as at least 2 new lesions on bone scan. Radiographic disease progression in soft tissue on CT/MRI was based on RECIST 1.1. CT/MRI and bone scans were read locally by the same radiologist (or nuclear medicine physician for interpretation of bone scans) whenever possible. Participants not known to have had radiographic progression at the time of analysis data cutoff were censored at the date of last radiographic assessment.
    Time Frame From randomization until the data cut-off date of 09 February 2015, median duration of treatment was 14.7 months in the enzalutamide arm and 8.4 months in the bicalutamide arm.

    Outcome Measure Data

    Analysis Population Description
    All participants with metastatic disease at study entry and randomly assigned to study treatment.
    Arm/Group Title Enzalutamide Bicalutamide
    Arm/Group Description Participants received enzalutamide 160 mg, self-administered as four 40-mg capsules, once per day by mouth and 1 bicalutamide-placebo capsule in DB phase. Participants received bicalutamide 50 mg, self-administered as 1 capsule, once per day by mouth and 4 enzalutamide-placebo capsules in DB phase.
    Measure Participants 128 129
    Median (95% Confidence Interval) [months]
    NA
    8.3
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Enzalutamide, Bicalutamide
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method Log Rank
    Comments P-value is based on an unstratified log-rank test.
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.324
    Confidence Interval (2-Sided) 95%
    0.211 to 0.497
    Parameter Dispersion Type:
    Value:
    Estimation Comments Hazard ratio is based on an unstratified Cox-regression model (with treatment as the only covariate) and is relative to bicalutamide with < 1 favoring enzalutamide.
    5. Secondary Outcome
    Title Quality of Life: Time to Degradation of Functional Assessment of Cancer Therapy - Prostate (FACT-P)
    Description The FACT-P is a multidimensional, self-reported quality of life instrument consisting of 27 core items that assess patient function in 4 domains: physical, social/family, emotional, and functional well-being, and supplemented by 12 site-specific items to assess for prostate-related symptoms. Each item is rated on a 0 to 4 Likert-type scale, and then combined to produce subscale scores for each domain, as well as a global quality of life score (0 to 156) with higher scores representing better quality of life. Time to degradation of FACT-P was defined as the time from randomization to first assessment with at least a 10-point decrease from baseline in the global FACT-P score for each participant. Participants with no score degradation at the time of analysis data cutoff were censored at the date of last assessment showing no degradation.
    Time Frame From randomization until the data cut-off date of 09 February 2015, median duration of treatment was 14.7 months in the enzalutamide arm and 8.4 months in the bicalutamide arm.

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat population: all participants randomly assigned to study treatment.
    Arm/Group Title Enzalutamide Bicalutamide
    Arm/Group Description Participants received enzalutamide 160 mg, self-administered as four 40-mg capsules, once per day by mouth and 1 bicalutamide-placebo capsule in DB phase. Participants received bicalutamide 50 mg, self-administered as 1 capsule, once per day by mouth and 4 enzalutamide-placebo capsules in DB phase.
    Measure Participants 198 198
    Median (95% Confidence Interval) [months]
    8.4
    8.3
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Enzalutamide, Bicalutamide
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.4945
    Comments This secondary endpoint was not adjusted for multiple comparisons.
    Method Log Rank
    Comments P-value is based on a log-rank test stratified by disease stage at study entry.
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.910
    Confidence Interval (2-Sided) 95%
    0.695 to 1.192
    Parameter Dispersion Type:
    Value:
    Estimation Comments Hazard ratio is based on a Cox regression model (with treatment as the only covariate) stratified by disease stage at study entry and is relative to bicalutamide with < 1 favoring enzalutamide.
    6. Secondary Outcome
    Title Best Overall Soft Tissue Response
    Description Best overall soft tissue response is defined as partial response (PR) or complete response (CR) while on study treatment based on investigator assessment of target, nontarget, and new lesions using RECIST 1.1. Only participants in the metastatic population with measurable soft tissue disease (at least 1 target lesion identified per RECIST 1.1) at screening were included in the analysis. All percentages are based on number of participants with metastatic and measurable soft tissue disease at screening in each treatment group.
    Time Frame From randomization until the data cut-off date of 09 February 2015, median duration of treatment was 14.7 months in the enzalutamide arm and 8.4 months in the bicalutamide arm.

    Outcome Measure Data

    Analysis Population Description
    All participants who were randomly assigned to study treatment and had metastatic and measurable soft tissue disease at screening.
    Arm/Group Title Enzalutamide Bicalutamide
    Arm/Group Description Participants received enzalutamide 160 mg, self-administered as four 40-mg capsules, once per day by mouth and 1 bicalutamide-placebo capsule in DB phase. Participants received bicalutamide 50 mg, self-administered as 1 capsule, once per day by mouth and 4 enzalutamide-placebo capsules in DB phase.
    Measure Participants 35 43
    Number (95% Confidence Interval) [percentage of participants]
    60.0
    30.3%
    14.0
    7.1%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Enzalutamide, Bicalutamide
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments This secondary endpoint was not adjusted for multiple comparisons.
    Method Cochran-Mantel-Haenszel
    Comments Based on unstratified Cochran-Mantel-Haenszel mean score test.
    Method of Estimation Estimation Parameter Difference in objective response rate
    Estimated Value 46.05
    Confidence Interval (2-Sided) 95%
    26.79 to 65.30
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    7. Secondary Outcome
    Title Percentage of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
    Description An AE was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. An SAE was an AE resulting in any of following outcomes or deemed significant for any other reason: death, initial or prolonged inpatient hospitalization, life-threatening experience (immediate risk of dying), persistent or significant disability or incapacity, congenital anomaly. A treatment emergent AE defined as an event that emerged during treatment period (From first dose of study drug until end of open label phase [up to maximum duration of 65 months]) that was absent before treatment, or worsened during treatment period relative to pre-treatment state. AE included both serious and non- SAE. Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. An AE was considered related to study drug if event was assessed by investigator as probably or possibly related.
    Time Frame From first dose of study drug until the end of open label phase (up to maximum duration of 65 months)

    Outcome Measure Data

    Analysis Population Description
    Safety population included all participants who received at least 1 dose of study drug.
    Arm/Group Title Enzalutamide DB Phase: Bicalutamide Open Label Phase: Bicalutamide Crossover to Enzalutamide
    Arm/Group Description Participants received enzalutamide 160 mg, self-administered as four 40-mg capsules, and 1 bicalutamide matching placebo capsule once per day, by mouth for up to 29 months in DB phase. Participants who completed DB phase and consented to participate in open label phase, received enzalutamide 160 mg, self-administered as four 40-mg capsules once per day by mouth for up to 36 months in open label phase. Participants received bicalutamide 50 mg, self-administered as 1 capsule, once per day by mouth and 4 enzalutamide matching placebo capsules for up to 29 months in DB phase. Participants who received bicalutamide 50 mg in DB phase and consented to participate in open label phase, received enzalutamide 160 mg, self-administered as four 40-mg capsules, once per day by mouth in open label phase for up to 36 months.
    Measure Participants 197 198 37
    Any AE
    96.4
    48.7%
    90.4
    45.7%
    97.3
    24.6%
    AE Leading to Study Drug Discontinuation
    16.2
    8.2%
    13.1
    6.6%
    24.3
    6.1%
    AE Leading to Death
    4.6
    2.3%
    3.0
    1.5%
    8.1
    2%
    Serious AE
    38.6
    19.5%
    30.3
    15.3%
    43.2
    10.9%
    AE Related to Study Drug
    66.5
    33.6%
    53.5
    27%
    70.3
    17.8%
    Serious AE Related to Study Drug
    7.6
    3.8%
    3.5
    1.8%
    2.7
    0.7%

    Adverse Events

    Time Frame From first dose of study drug until the end of open label phase (up to maximum duration of 65 months)
    Adverse Event Reporting Description Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
    Arm/Group Title Enzalutamide DB Phase: Bicalutamide Open Label Phase: Bicalutamide Crossover to Enzalutamide
    Arm/Group Description Participants received enzalutamide 160 mg, self-administered as four 40-mg capsules, once per day by mouth and 1 bicalutamide-placebo capsule for up to 29 months in DB phase. Participants who completed DB phase and consented to participate in open label phase, received same treatment for up to 36 months in open label phase. Participants received bicalutamide 50 mg, self-administered as 1 capsule, once per day by mouth and 4 enzalutamide-placebo capsules for up to 29 months in DB phase. Participants who received bicalutamide 50 mg in DB phase and consented to participate in open label phase, received enzalutamide 160 mg, self-administered as four 40-mg capsules, once per day by mouth in open label phase for up to 36 months.
    All Cause Mortality
    Enzalutamide DB Phase: Bicalutamide Open Label Phase: Bicalutamide Crossover to Enzalutamide
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Enzalutamide DB Phase: Bicalutamide Open Label Phase: Bicalutamide Crossover to Enzalutamide
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 76/197 (38.6%) 60/198 (30.3%) 16/37 (43.2%)
    Blood and lymphatic system disorders
    Anaemia 4/197 (2%) 4/198 (2%) 2/37 (5.4%)
    Lymphadenitis 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Cardiac disorders
    Acute coronary syndrome 2/197 (1%) 0/198 (0%) 0/37 (0%)
    Acute myocardial infarction 2/197 (1%) 1/198 (0.5%) 1/37 (2.7%)
    Angina pectoris 5/197 (2.5%) 0/198 (0%) 0/37 (0%)
    Aortic valve disease 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Atrial fibrillation 2/197 (1%) 1/198 (0.5%) 0/37 (0%)
    Atrial flutter 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Atrioventricular block 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Bradycardia 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Cardiac failure 1/197 (0.5%) 1/198 (0.5%) 1/37 (2.7%)
    Cardiac failure congestive 5/197 (2.5%) 2/198 (1%) 2/37 (5.4%)
    Cardio-respiratory arrest 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Coronary artery disease 1/197 (0.5%) 1/198 (0.5%) 0/37 (0%)
    Palpitations 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Stress cardiomyopathy 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Supraventricular tachycardia 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Ventricular tachycardia 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Myocardial infarction 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Ventricular fibrillation 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Arrhythmia 0/197 (0%) 0/198 (0%) 1/37 (2.7%)
    Atrioventricular block complete 0/197 (0%) 0/198 (0%) 1/37 (2.7%)
    Ear and labyrinth disorders
    Vertigo 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Endocrine disorders
    Inappropriate antidiuretic hormone secretion 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Gastrointestinal disorders
    Abdominal pain 0/197 (0%) 1/198 (0.5%) 1/37 (2.7%)
    Constipation 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Diarrhoea 2/197 (1%) 0/198 (0%) 0/37 (0%)
    Diverticulum intestinal haemorrhagic 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Duodenal ulcer 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Dysphagia 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Gastric haemorrhage 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Gastric ulcer 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Gastrointestinal haemorrhage 2/197 (1%) 0/198 (0%) 0/37 (0%)
    Ileus 2/197 (1%) 0/198 (0%) 0/37 (0%)
    Large intestinal stenosis 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Odynophagia 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Rectal haemorrhage 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Small intestinal obstruction 1/197 (0.5%) 1/198 (0.5%) 0/37 (0%)
    Upper gastrointestinal haemorrhage 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Duodenal perforation 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Lower gastrointestinal haemorrhage 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Ascites 0/197 (0%) 0/198 (0%) 1/37 (2.7%)
    Duodenal ulcer perforation 0/197 (0%) 0/198 (0%) 1/37 (2.7%)
    General disorders
    Asthenia 5/197 (2.5%) 1/198 (0.5%) 0/37 (0%)
    Chest pain 2/197 (1%) 0/198 (0%) 0/37 (0%)
    Device occlusion 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Fatigue 1/197 (0.5%) 2/198 (1%) 0/37 (0%)
    General physical health deterioration 1/197 (0.5%) 1/198 (0.5%) 0/37 (0%)
    Non-cardiac chest pain 1/197 (0.5%) 1/198 (0.5%) 0/37 (0%)
    Pyrexia 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Disease progression 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Hepatobiliary disorders
    Cholecystitis acute 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Cholecystitis chronic 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Hepatic failure 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Infections and infestations
    Bronchitis 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Cellulitis 3/197 (1.5%) 0/198 (0%) 0/37 (0%)
    Hepatitis B 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Lobar pneumonia 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Peritonitis 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Pneumonia 6/197 (3%) 4/198 (2%) 0/37 (0%)
    Pulmonary sepsis 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Pyelonephritis 1/197 (0.5%) 2/198 (1%) 0/37 (0%)
    Pyelonephritis acute 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Sepsis 1/197 (0.5%) 3/198 (1.5%) 1/37 (2.7%)
    Septic shock 1/197 (0.5%) 2/198 (1%) 0/37 (0%)
    Skin infection 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Subcutaneous abscess 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Urinary tract infection 2/197 (1%) 6/198 (3%) 1/37 (2.7%)
    Urosepsis 1/197 (0.5%) 3/198 (1.5%) 0/37 (0%)
    Appendicitis perforated 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Cystitis 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Urinary bladder abscess 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Appendicitis 0/197 (0%) 0/198 (0%) 1/37 (2.7%)
    Wound infection 0/197 (0%) 0/198 (0%) 1/37 (2.7%)
    Device related infection 0/197 (0%) 0/198 (0%) 1/37 (2.7%)
    Osteomyelitis 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Postoperative wound infection 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Injury, poisoning and procedural complications
    Fall 5/197 (2.5%) 0/198 (0%) 1/37 (2.7%)
    Head injury 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Hip fracture 2/197 (1%) 1/198 (0.5%) 1/37 (2.7%)
    Injury 0/197 (0%) 2/198 (1%) 0/37 (0%)
    Overdose 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Pubis fracture 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Rib fracture 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Spinal compression fracture 1/197 (0.5%) 1/198 (0.5%) 0/37 (0%)
    Subdural haematoma 2/197 (1%) 0/198 (0%) 0/37 (0%)
    Craniocerebral injury 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Femoral neck fracture 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Urinary bladder rupture 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Alcohol poisoning 0/197 (0%) 0/198 (0%) 1/37 (2.7%)
    Cystitis radiation 0/197 (0%) 0/198 (0%) 2/37 (5.4%)
    Radius fracture 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Ulna fracture 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Femur fracture 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Investigations
    Alanine aminotransferase increased 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Aspartate aminotransferase increased 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Liver function test abnormal 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    International normalised ratio increased 0/197 (0%) 0/198 (0%) 1/37 (2.7%)
    Troponin increased 0/197 (0%) 0/198 (0%) 1/37 (2.7%)
    Metabolism and nutrition disorders
    Decreased appetite 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Dehydration 2/197 (1%) 1/198 (0.5%) 1/37 (2.7%)
    Diabetic ketoacidosis 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Gout 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Hypercalcaemia 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Hyperglycaemia 2/197 (1%) 0/198 (0%) 0/37 (0%)
    Hypoglycaemia 0/197 (0%) 1/198 (0.5%) 1/37 (2.7%)
    Hypokalaemia 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Hypovolaemia 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Malnutrition 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 2/197 (1%) 0/198 (0%) 0/37 (0%)
    Back pain 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Intervertebral disc displacement 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Lumbar spinal stenosis 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Muscular weakness 2/197 (1%) 0/198 (0%) 0/37 (0%)
    Musculoskeletal pain 2/197 (1%) 0/198 (0%) 0/37 (0%)
    Osteoarthritis 1/197 (0.5%) 0/198 (0%) 1/37 (2.7%)
    Pathological fracture 1/197 (0.5%) 2/198 (1%) 0/37 (0%)
    Spinal column stenosis 0/197 (0%) 0/198 (0%) 1/37 (2.7%)
    Spondylolisthesis 0/197 (0%) 0/198 (0%) 1/37 (2.7%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Adenocarcinoma of colon 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Bladder transitional cell carcinoma 1/197 (0.5%) 1/198 (0.5%) 0/37 (0%)
    Cancer pain 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Colon cancer 1/197 (0.5%) 1/198 (0.5%) 0/37 (0%)
    Colon cancer metastatic 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Erythroleukaemia 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Intraductal papillary mucinous neoplasm 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Metastases to adrenals 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Metastases to liver 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Metastases to spine 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Metastatic pain 1/197 (0.5%) 1/198 (0.5%) 0/37 (0%)
    Myelofibrosis 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Pancreatic carcinoma 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Prostate cancer metastatic 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Renal cell carcinoma 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Squamous cell carcinoma of lung 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Squamous cell carcinoma of skin 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Transitional cell carcinoma 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Tumour necrosis 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Basal cell carcinoma 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Bladder cancer 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Cholangiocarcinoma 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Small cell lung cancer 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Malignant melanoma 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Nervous system disorders
    Amnesia 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Carotid artery stenosis 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Cerebrovascular accident 2/197 (1%) 0/198 (0%) 0/37 (0%)
    Cervical cord compression 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Convulsion 2/197 (1%) 0/198 (0%) 0/37 (0%)
    Dizziness 1/197 (0.5%) 0/198 (0%) 1/37 (2.7%)
    Encephalopathy 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Headache 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Hemiparesis 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Hypoglycaemic encephalopathy 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Metabolic encephalopathy 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Presyncope 2/197 (1%) 0/198 (0%) 0/37 (0%)
    Syncope 3/197 (1.5%) 2/198 (1%) 1/37 (2.7%)
    Transient ischaemic attack 5/197 (2.5%) 1/198 (0.5%) 0/37 (0%)
    Cognitive disorder 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Subarachnoid haemorrhage 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Dyskinesia 0/197 (0%) 0/198 (0%) 1/37 (2.7%)
    Haemorrhage intracranial 0/197 (0%) 0/198 (0%) 1/37 (2.7%)
    Haemorrhagic stroke 0/197 (0%) 0/198 (0%) 2/37 (5.4%)
    Hydrocephalus 0/197 (0%) 0/198 (0%) 1/37 (2.7%)
    Psychiatric disorders
    Delirium 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Mental status changes 2/197 (1%) 0/198 (0%) 0/37 (0%)
    Suicide attempt 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Renal and urinary disorders
    Bladder obstruction 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Bladder outlet obstruction 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Calculus bladder 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Dysuria 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Haematuria 5/197 (2.5%) 4/198 (2%) 1/37 (2.7%)
    Hydronephrosis 4/197 (2%) 1/198 (0.5%) 0/37 (0%)
    Nephrolithiasis 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Postrenal failure 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Renal failure 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Renal failure acute 1/197 (0.5%) 1/198 (0.5%) 0/37 (0%)
    Urinary retention 1/197 (0.5%) 2/198 (1%) 1/37 (2.7%)
    Urinary tract obstruction 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Vesical fistula 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Cystitis haemorrhagic 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Obstructive uropathy 1/197 (0.5%) 1/198 (0.5%) 0/37 (0%)
    Urethral stenosis 0/197 (0%) 0/198 (0%) 1/37 (2.7%)
    Reproductive system and breast disorders
    Prostatic calcification 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Respiratory, thoracic and mediastinal disorders
    Asthma 1/197 (0.5%) 1/198 (0.5%) 0/37 (0%)
    Chronic obstructive pulmonary disease 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Pleural effusion 1/197 (0.5%) 1/198 (0.5%) 0/37 (0%)
    Pneumothorax 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Pulmonary embolism 1/197 (0.5%) 2/198 (1%) 0/37 (0%)
    Pulmonary oedema 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Respiratory failure 0/197 (0%) 3/198 (1.5%) 0/37 (0%)
    Acute respiratory failure 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Epistaxis 0/197 (0%) 0/198 (0%) 1/37 (2.7%)
    Skin and subcutaneous tissue disorders
    Dermatitis psoriasiform 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Rash maculo-papular 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Skin ulcer 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Surgical and medical procedures
    Umbilical hernia repair 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Vascular disorders
    Accelerated hypertension 2/197 (1%) 0/198 (0%) 0/37 (0%)
    Aortic stenosis 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Deep vein thrombosis 0/197 (0%) 3/198 (1.5%) 0/37 (0%)
    Hypertension 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Hypotension 2/197 (1%) 1/198 (0.5%) 0/37 (0%)
    Peripheral artery thrombosis 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Orthostatic hypotension 0/197 (0%) 0/198 (0%) 1/37 (2.7%)
    Other (Not Including Serious) Adverse Events
    Enzalutamide DB Phase: Bicalutamide Open Label Phase: Bicalutamide Crossover to Enzalutamide
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 187/197 (94.9%) 179/198 (90.4%) 36/37 (97.3%)
    Blood and lymphatic system disorders
    Haemorrhagic anaemia 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Increased tendency to bruise 2/197 (1%) 0/198 (0%) 1/37 (2.7%)
    Iron deficiency anaemia 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Leukocytosis 2/197 (1%) 1/198 (0.5%) 0/37 (0%)
    Anaemia 22/197 (11.2%) 21/198 (10.6%) 3/37 (8.1%)
    Lymphadenitis 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Lymphadenopathy 2/197 (1%) 0/198 (0%) 0/37 (0%)
    Neutropenia 3/197 (1.5%) 0/198 (0%) 0/37 (0%)
    Pancytopenia 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Thrombocytopenia 1/197 (0.5%) 3/198 (1.5%) 0/37 (0%)
    Cardiac disorders
    Angina pectoris 2/197 (1%) 1/198 (0.5%) 0/37 (0%)
    Aortic valve disease 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Aortic valve stenosis 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Arrhythmia 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Arteriosclerosis coronary artery 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Atrial fibrillation 4/197 (2%) 5/198 (2.5%) 3/37 (8.1%)
    Atrial flutter 0/197 (0%) 0/198 (0%) 1/37 (2.7%)
    Atrial thrombosis 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Atrioventricular block second degree 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Bradycardia 2/197 (1%) 2/198 (1%) 1/37 (2.7%)
    Cardiac failure congestive 4/197 (2%) 3/198 (1.5%) 2/37 (5.4%)
    Cardiomegaly 0/197 (0%) 1/198 (0.5%) 1/37 (2.7%)
    Coronary artery disease 0/197 (0%) 0/198 (0%) 1/37 (2.7%)
    Mitral valve incompetence 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Myocardial ischaemia 0/197 (0%) 0/198 (0%) 1/37 (2.7%)
    Palpitations 2/197 (1%) 1/198 (0.5%) 0/37 (0%)
    Sick sinus syndrome 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Sinus bradycardia 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Sinus tachycardia 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Supraventricular tachycardia 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Tachycardia 1/197 (0.5%) 3/198 (1.5%) 0/37 (0%)
    Ventricular extrasystoles 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Ventricular tachycardia 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Cardiomyopathy 1/197 (0.5%) 1/198 (0.5%) 0/37 (0%)
    Congenital, familial and genetic disorders
    Branchial cyst 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Phimosis 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Type V hyperlipidaemia 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Ear and labyrinth disorders
    Cerumen impaction 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Deafness 0/197 (0%) 0/198 (0%) 1/37 (2.7%)
    Deafness bilateral 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Ear discomfort 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Ear haemorrhage 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Ear pain 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Hearing impaired 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Otorrhoea 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Tinnitus 2/197 (1%) 1/198 (0.5%) 0/37 (0%)
    Vertigo 1/197 (0.5%) 1/198 (0.5%) 0/37 (0%)
    Vertigo positional 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Vestibular disorder 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Endocrine disorders
    Hyperparathyroidism 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Hypothyroidism 5/197 (2.5%) 1/198 (0.5%) 0/37 (0%)
    Inappropriate antidiuretic hormone secretion 0/197 (0%) 1/198 (0.5%) 1/37 (2.7%)
    Thyroid cyst 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Eye disorders
    Astigmatism 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Cataract 4/197 (2%) 3/198 (1.5%) 1/37 (2.7%)
    Cataract nuclear 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Conjunctivitis 3/197 (1.5%) 0/198 (0%) 1/37 (2.7%)
    Diabetic retinopathy 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Dry eye 0/197 (0%) 1/198 (0.5%) 1/37 (2.7%)
    Eye irritation 1/197 (0.5%) 1/198 (0.5%) 0/37 (0%)
    Eye pain 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Eye pruritus 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Lacrimation increased 3/197 (1.5%) 0/198 (0%) 0/37 (0%)
    Macular degeneration 1/197 (0.5%) 1/198 (0.5%) 0/37 (0%)
    Ocular hyperaemia 1/197 (0.5%) 1/198 (0.5%) 0/37 (0%)
    Photophobia 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Posterior capsule opacification 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Retinal tear 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Vision blurred 4/197 (2%) 2/198 (1%) 0/37 (0%)
    Visual impairment 4/197 (2%) 0/198 (0%) 0/37 (0%)
    Gastrointestinal disorders
    Abdominal pain 15/197 (7.6%) 6/198 (3%) 1/37 (2.7%)
    Constipation 29/197 (14.7%) 33/198 (16.7%) 6/37 (16.2%)
    Diarrhoea 26/197 (13.2%) 29/198 (14.6%) 9/37 (24.3%)
    Nausea 38/197 (19.3%) 32/198 (16.2%) 9/37 (24.3%)
    Vomiting 12/197 (6.1%) 17/198 (8.6%) 3/37 (8.1%)
    Abdominal adhesions 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Abdominal discomfort 4/197 (2%) 2/198 (1%) 0/37 (0%)
    Abdominal distension 4/197 (2%) 3/198 (1.5%) 0/37 (0%)
    Abdominal hernia 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Abdominal pain lower 3/197 (1.5%) 3/198 (1.5%) 0/37 (0%)
    Abdominal pain upper 3/197 (1.5%) 2/198 (1%) 0/37 (0%)
    Abdominal tenderness 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Acquired oesophageal web 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Anal fissure 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Ascites 1/197 (0.5%) 1/198 (0.5%) 0/37 (0%)
    Bowel movement irregularity 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Colitis 1/197 (0.5%) 1/198 (0.5%) 0/37 (0%)
    Colitis ulcerative 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Defaecation urgency 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Diverticulum 3/197 (1.5%) 2/198 (1%) 0/37 (0%)
    Dry mouth 3/197 (1.5%) 2/198 (1%) 0/37 (0%)
    Duodenal ulcer 0/197 (0%) 0/198 (0%) 1/37 (2.7%)
    Duodenitis 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Dyspepsia 6/197 (3%) 5/198 (2.5%) 1/37 (2.7%)
    Dysphagia 4/197 (2%) 4/198 (2%) 0/37 (0%)
    Erosive oesophagitis 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Faecal incontinence 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Faeces discoloured 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Flatulence 9/197 (4.6%) 5/198 (2.5%) 0/37 (0%)
    Frequent bowel movements 1/197 (0.5%) 1/198 (0.5%) 0/37 (0%)
    Gastric haemorrhage 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Gastric ulcer 4/197 (2%) 1/198 (0.5%) 0/37 (0%)
    Gastritis 8/197 (4.1%) 2/198 (1%) 0/37 (0%)
    Gastritis haemorrhagic 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Gastrointestinal angiodysplasia 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Gastrointestinal disorder 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Gastrointestinal haemorrhage 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Gastrointestinal pain 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Gastrooesophageal reflux disease 10/197 (5.1%) 2/198 (1%) 6/37 (16.2%)
    Gingival swelling 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Haematochezia 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Haemorrhoids 2/197 (1%) 2/198 (1%) 0/37 (0%)
    Hiatus hernia 2/197 (1%) 2/198 (1%) 0/37 (0%)
    Ileus 0/197 (0%) 0/198 (0%) 1/37 (2.7%)
    Impaired gastric emptying 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Large intestine polyp 0/197 (0%) 2/198 (1%) 0/37 (0%)
    Mesenteric artery stenosis 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Mouth haemorrhage 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Oesophageal achalasia 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Oesophageal dilatation 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Oesophageal disorder 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Oesophageal stenosis 0/197 (0%) 2/198 (1%) 0/37 (0%)
    Oesophagitis 3/197 (1.5%) 0/198 (0%) 0/37 (0%)
    Pancreatic atrophy 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Pancreatic cyst 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Rectal discharge 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Rectal haemorrhage 3/197 (1.5%) 1/198 (0.5%) 1/37 (2.7%)
    Rectal tenesmus 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Retching 1/197 (0.5%) 1/198 (0.5%) 1/37 (2.7%)
    Salivary hypersecretion 0/197 (0%) 0/198 (0%) 1/37 (2.7%)
    Stomatitis 1/197 (0.5%) 1/198 (0.5%) 0/37 (0%)
    Tongue discolouration 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Tongue ulceration 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Tooth loss 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Toothache 3/197 (1.5%) 2/198 (1%) 0/37 (0%)
    Umbilical hernia 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    General disorders
    Asthenia 16/197 (8.1%) 5/198 (2.5%) 2/37 (5.4%)
    Fatigue 82/197 (41.6%) 56/198 (28.3%) 10/37 (27%)
    Pyrexia 5/197 (2.5%) 12/198 (6.1%) 1/37 (2.7%)
    Chest discomfort 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Chest pain 6/197 (3%) 2/198 (1%) 0/37 (0%)
    Chills 5/197 (2.5%) 2/198 (1%) 0/37 (0%)
    Device dislocation 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Device occlusion 0/197 (0%) 1/198 (0.5%) 1/37 (2.7%)
    Discomfort 0/197 (0%) 0/198 (0%) 1/37 (2.7%)
    Early satiety 3/197 (1.5%) 1/198 (0.5%) 0/37 (0%)
    Face oedema 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Gait disturbance 6/197 (3%) 1/198 (0.5%) 1/37 (2.7%)
    Generalised oedema 0/197 (0%) 3/198 (1.5%) 0/37 (0%)
    Inflammation 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Influenza like illness 5/197 (2.5%) 5/198 (2.5%) 0/37 (0%)
    Injection site reaction 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Local swelling 4/197 (2%) 1/198 (0.5%) 0/37 (0%)
    Localised oedema 2/197 (1%) 0/198 (0%) 0/37 (0%)
    Malaise 1/197 (0.5%) 2/198 (1%) 0/37 (0%)
    Mucosal inflammation 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Oedema 2/197 (1%) 1/198 (0.5%) 0/37 (0%)
    Oedema peripheral 17/197 (8.6%) 10/198 (5.1%) 1/37 (2.7%)
    Pain 7/197 (3.6%) 5/198 (2.5%) 0/37 (0%)
    Suprapubic pain 0/197 (0%) 0/198 (0%) 1/37 (2.7%)
    Temperature intolerance 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Thirst 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Non-cardiac chest pain 2/197 (1%) 5/198 (2.5%) 0/37 (0%)
    Hepatobiliary disorders
    Cholangitis 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Cholelithiasis 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Gallbladder disorder 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Hepatic cirrhosis 0/197 (0%) 2/198 (1%) 0/37 (0%)
    Hyperbilirubinaemia 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Liver injury 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Immune system disorders
    Drug hypersensitivity 0/197 (0%) 0/198 (0%) 1/37 (2.7%)
    Seasonal allergy 2/197 (1%) 1/198 (0.5%) 0/37 (0%)
    Infections and infestations
    Abscess limb 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Abscess soft tissue 0/197 (0%) 0/198 (0%) 1/37 (2.7%)
    Acute sinusitis 2/197 (1%) 0/198 (0%) 1/37 (2.7%)
    Appendicitis 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Asymptomatic bacteriuria 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Axillary candidiasis 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Bacteraemia 1/197 (0.5%) 1/198 (0.5%) 0/37 (0%)
    Bacterial disease carrier 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Bacteriuria 0/197 (0%) 1/198 (0.5%) 1/37 (2.7%)
    Bronchitis 7/197 (3.6%) 1/198 (0.5%) 0/37 (0%)
    Candida infection 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Cellulitis 5/197 (2.5%) 1/198 (0.5%) 0/37 (0%)
    Chronic sinusitis 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Cystitis 1/197 (0.5%) 0/198 (0%) 1/37 (2.7%)
    Diverticulitis 3/197 (1.5%) 0/198 (0%) 0/37 (0%)
    Ear infection 1/197 (0.5%) 2/198 (1%) 0/37 (0%)
    Fungal infection 1/197 (0.5%) 0/198 (0%) 1/37 (2.7%)
    Furuncle 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Gastroenteritis viral 2/197 (1%) 0/198 (0%) 0/37 (0%)
    Genital infection fungal 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Gingival infection 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Gingivitis 2/197 (1%) 0/198 (0%) 0/37 (0%)
    Helicobacter infection 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Hepatitis B 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Herpes zoster 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Hordeolum 1/197 (0.5%) 1/198 (0.5%) 0/37 (0%)
    Incision site infection 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Infected cyst 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Influenza 5/197 (2.5%) 1/198 (0.5%) 0/37 (0%)
    Kidney infection 0/197 (0%) 0/198 (0%) 1/37 (2.7%)
    Klebsiella bacteraemia 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Lobar pneumonia 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Mucosal infection 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Nasopharyngitis 8/197 (4.1%) 11/198 (5.6%) 0/37 (0%)
    Onychomycosis 2/197 (1%) 1/198 (0.5%) 0/37 (0%)
    Oral candidiasis 2/197 (1%) 0/198 (0%) 0/37 (0%)
    Oral herpes 0/197 (0%) 1/198 (0.5%) 1/37 (2.7%)
    Oropharyngitis fungal 0/197 (0%) 0/198 (0%) 1/37 (2.7%)
    Otitis externa 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Otitis media 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Peripheral nerve infection 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Peritonitis 1/197 (0.5%) 0/198 (0%) 1/37 (2.7%)
    Pharyngitis 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Pneumonia 5/197 (2.5%) 6/198 (3%) 1/37 (2.7%)
    Postoperative wound infection 2/197 (1%) 0/198 (0%) 0/37 (0%)
    Respiratory tract infection 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Rhinitis 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Sinusitis 6/197 (3%) 5/198 (2.5%) 0/37 (0%)
    Skin infection 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Tinea infection 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Tinea pedis 4/197 (2%) 0/198 (0%) 0/37 (0%)
    Tooth abscess 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Tooth infection 1/197 (0.5%) 2/198 (1%) 0/37 (0%)
    Upper respiratory tract infection 8/197 (4.1%) 8/198 (4%) 0/37 (0%)
    Urinary bladder abscess 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Urinary tract infection 14/197 (7.1%) 21/198 (10.6%) 7/37 (18.9%)
    Viral upper respiratory tract infection 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Wound infection 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Wound infection staphylococcal 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Injury, poisoning and procedural complications
    Alcohol poisoning 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Ankle fracture 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Clavicle fracture 1/197 (0.5%) 1/198 (0.5%) 0/37 (0%)
    Compression fracture 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Contrast media reaction 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Contusion 5/197 (2.5%) 1/198 (0.5%) 0/37 (0%)
    Cystitis radiation 1/197 (0.5%) 1/198 (0.5%) 1/37 (2.7%)
    Eschar 0/197 (0%) 0/198 (0%) 1/37 (2.7%)
    Excoriation 3/197 (1.5%) 1/198 (0.5%) 0/37 (0%)
    Facial bones fracture 1/197 (0.5%) 2/198 (1%) 0/37 (0%)
    Fall 39/197 (19.8%) 19/198 (9.6%) 8/37 (21.6%)
    Femoral neck fracture 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Fibula fracture 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Foot fracture 1/197 (0.5%) 1/198 (0.5%) 0/37 (0%)
    Fracture 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Fractured coccyx 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Hand fracture 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Head injury 2/197 (1%) 1/198 (0.5%) 0/37 (0%)
    Humerus fracture 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Incision site pain 2/197 (1%) 0/198 (0%) 0/37 (0%)
    Joint injury 1/197 (0.5%) 2/198 (1%) 0/37 (0%)
    Laceration 10/197 (5.1%) 3/198 (1.5%) 0/37 (0%)
    Limb injury 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Lumbar vertebral fracture 0/197 (0%) 1/198 (0.5%) 1/37 (2.7%)
    Meniscus injury 0/197 (0%) 0/198 (0%) 1/37 (2.7%)
    Muscle strain 2/197 (1%) 0/198 (0%) 0/37 (0%)
    Procedural pain 1/197 (0.5%) 4/198 (2%) 2/37 (5.4%)
    Radiation injury 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Radiation pneumonitis 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Radius fracture 4/197 (2%) 0/198 (0%) 0/37 (0%)
    Rib fracture 7/197 (3.6%) 6/198 (3%) 0/37 (0%)
    Skeletal injury 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Spinal column injury 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Spinal compression fracture 4/197 (2%) 1/198 (0.5%) 0/37 (0%)
    Splinter 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Stress fracture 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Thoracic vertebral fracture 0/197 (0%) 0/198 (0%) 1/37 (2.7%)
    Vth nerve injury 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Wound 2/197 (1%) 1/198 (0.5%) 0/37 (0%)
    Bone contusion 3/197 (1.5%) 0/198 (0%) 0/37 (0%)
    Investigations
    Alanine aminotransferase increased 1/197 (0.5%) 3/198 (1.5%) 0/37 (0%)
    Aspartate aminotransferase increased 1/197 (0.5%) 5/198 (2.5%) 0/37 (0%)
    Blood albumin decreased 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Blood alkaline phosphatase increased 5/197 (2.5%) 11/198 (5.6%) 0/37 (0%)
    Blood bicarbonate decreased 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Blood bilirubin increased 3/197 (1.5%) 1/198 (0.5%) 0/37 (0%)
    Blood calcium increased 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Blood cholesterol increased 2/197 (1%) 2/198 (1%) 0/37 (0%)
    Blood creatine phosphokinase increased 6/197 (3%) 7/198 (3.5%) 0/37 (0%)
    Blood creatinine increased 5/197 (2.5%) 7/198 (3.5%) 1/37 (2.7%)
    Blood glucose increased 0/197 (0%) 3/198 (1.5%) 1/37 (2.7%)
    Blood lactate dehydrogenase increased 1/197 (0.5%) 4/198 (2%) 0/37 (0%)
    Blood lactic acid increased 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Blood parathyroid hormone increased 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Blood potassium increased 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Blood pressure increased 3/197 (1.5%) 1/198 (0.5%) 2/37 (5.4%)
    Blood sodium decreased 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Blood urine present 1/197 (0.5%) 1/198 (0.5%) 0/37 (0%)
    Cardiac murmur 1/197 (0.5%) 1/198 (0.5%) 0/37 (0%)
    Face and mouth X-ray abnormal 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Haemoglobin decreased 0/197 (0%) 4/198 (2%) 1/37 (2.7%)
    Helicobacter test positive 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    International normalised ratio fluctuation 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    International normalised ratio increased 1/197 (0.5%) 2/198 (1%) 0/37 (0%)
    Intraocular pressure increased 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Low density lipoprotein increased 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Lymphocyte count decreased 2/197 (1%) 0/198 (0%) 0/37 (0%)
    Lymphocyte count increased 1/197 (0.5%) 1/198 (0.5%) 0/37 (0%)
    Neutrophil count decreased 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Neutrophil count increased 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Occult blood positive 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Platelet count decreased 4/197 (2%) 0/198 (0%) 0/37 (0%)
    Protein total decreased 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Protein total increased 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Red blood cell count decreased 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Residual urine volume increased 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Urine ketone body present 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Urine leukocyte esterase positive 1/197 (0.5%) 1/198 (0.5%) 0/37 (0%)
    Vitamin D increased 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Weight decreased 16/197 (8.1%) 13/198 (6.6%) 3/37 (8.1%)
    Weight increased 1/197 (0.5%) 1/198 (0.5%) 0/37 (0%)
    White blood cell count decreased 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    White blood cell count increased 1/197 (0.5%) 1/198 (0.5%) 0/37 (0%)
    Haematocrit decreased 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Blood urea increased 1/197 (0.5%) 2/198 (1%) 0/37 (0%)
    Hepatic enzyme increased 1/197 (0.5%) 0/198 (0%) 1/37 (2.7%)
    Metabolism and nutrition disorders
    Acidosis 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Decreased appetite 28/197 (14.2%) 17/198 (8.6%) 6/37 (16.2%)
    Dehydration 13/197 (6.6%) 6/198 (3%) 1/37 (2.7%)
    Diabetes mellitus 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Diabetes mellitus inadequate control 1/197 (0.5%) 1/198 (0.5%) 0/37 (0%)
    Failure to thrive 2/197 (1%) 0/198 (0%) 0/37 (0%)
    Gout 3/197 (1.5%) 3/198 (1.5%) 0/37 (0%)
    Hypercalcaemia 1/197 (0.5%) 1/198 (0.5%) 0/37 (0%)
    Hyperchloraemia 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Hypercholesterolaemia 5/197 (2.5%) 1/198 (0.5%) 3/37 (8.1%)
    Hyperglycaemia 11/197 (5.6%) 14/198 (7.1%) 2/37 (5.4%)
    Hyperkalaemia 6/197 (3%) 4/198 (2%) 0/37 (0%)
    Hyperlipidaemia 1/197 (0.5%) 1/198 (0.5%) 0/37 (0%)
    Hypermagnesaemia 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Hypernatraemia 1/197 (0.5%) 1/198 (0.5%) 0/37 (0%)
    Hypoalbuminaemia 3/197 (1.5%) 4/198 (2%) 0/37 (0%)
    Hypocalcaemia 3/197 (1.5%) 4/198 (2%) 1/37 (2.7%)
    Hypoglycaemia 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Hypokalaemia 13/197 (6.6%) 11/198 (5.6%) 2/37 (5.4%)
    Hypomagnesaemia 4/197 (2%) 4/198 (2%) 1/37 (2.7%)
    Hyponatraemia 10/197 (5.1%) 4/198 (2%) 2/37 (5.4%)
    Hypophosphataemia 1/197 (0.5%) 2/198 (1%) 0/37 (0%)
    Increased appetite 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Insulin resistance 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Iron deficiency 1/197 (0.5%) 0/198 (0%) 1/37 (2.7%)
    Lactic acidosis 1/197 (0.5%) 1/198 (0.5%) 1/37 (2.7%)
    Malnutrition 0/197 (0%) 2/198 (1%) 1/37 (2.7%)
    Metabolic acidosis 2/197 (1%) 0/198 (0%) 0/37 (0%)
    Polydipsia 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Type 1 diabetes mellitus 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Type 2 diabetes mellitus 2/197 (1%) 0/198 (0%) 0/37 (0%)
    Vitamin B complex deficiency 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Vitamin B12 deficiency 3/197 (1.5%) 0/198 (0%) 1/37 (2.7%)
    Vitamin D deficiency 1/197 (0.5%) 0/198 (0%) 1/37 (2.7%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 45/197 (22.8%) 29/198 (14.6%) 5/37 (13.5%)
    Back pain 41/197 (20.8%) 34/198 (17.2%) 3/37 (8.1%)
    Muscular weakness 13/197 (6.6%) 6/198 (3%) 1/37 (2.7%)
    Musculoskeletal pain 16/197 (8.1%) 11/198 (5.6%) 2/37 (5.4%)
    Pain in extremity 23/197 (11.7%) 10/198 (5.1%) 1/37 (2.7%)
    Bone pain 6/197 (3%) 2/198 (1%) 2/37 (5.4%)
    Bunion 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Bursitis 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Cervical spinal stenosis 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Coccydynia 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Costochondritis 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Exostosis 2/197 (1%) 0/198 (0%) 0/37 (0%)
    Flank pain 3/197 (1.5%) 5/198 (2.5%) 1/37 (2.7%)
    Foot deformity 2/197 (1%) 1/198 (0.5%) 0/37 (0%)
    Groin pain 6/197 (3%) 4/198 (2%) 0/37 (0%)
    Intervertebral disc compression 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Intervertebral disc degeneration 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Joint crepitation 0/197 (0%) 2/198 (1%) 1/37 (2.7%)
    Joint instability 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Joint stiffness 2/197 (1%) 0/198 (0%) 0/37 (0%)
    Joint swelling 0/197 (0%) 2/198 (1%) 0/37 (0%)
    Limb discomfort 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Lumbar spinal stenosis 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Mobility decreased 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Muscle atrophy 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Muscle haemorrhage 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Muscle spasms 7/197 (3.6%) 6/198 (3%) 1/37 (2.7%)
    Muscle tightness 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Muscle twitching 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Musculoskeletal chest pain 13/197 (6.6%) 4/198 (2%) 2/37 (5.4%)
    Musculoskeletal discomfort 1/197 (0.5%) 1/198 (0.5%) 0/37 (0%)
    Musculoskeletal disorder 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Musculoskeletal stiffness 3/197 (1.5%) 0/198 (0%) 0/37 (0%)
    Myalgia 10/197 (5.1%) 5/198 (2.5%) 1/37 (2.7%)
    Neck pain 5/197 (2.5%) 4/198 (2%) 2/37 (5.4%)
    Osteoarthritis 7/197 (3.6%) 1/198 (0.5%) 0/37 (0%)
    Osteolysis 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Osteopenia 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Osteoporosis 3/197 (1.5%) 0/198 (0%) 0/37 (0%)
    Pain in jaw 1/197 (0.5%) 1/198 (0.5%) 0/37 (0%)
    Pathological fracture 0/197 (0%) 1/198 (0.5%) 1/37 (2.7%)
    Plantar fasciitis 3/197 (1.5%) 0/198 (0%) 0/37 (0%)
    Psoriatic arthropathy 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Rotator cuff syndrome 2/197 (1%) 0/198 (0%) 0/37 (0%)
    Scoliosis 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Spinal column stenosis 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Spinal disorder 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Spinal osteoarthritis 2/197 (1%) 0/198 (0%) 0/37 (0%)
    Spinal pain 1/197 (0.5%) 0/198 (0%) 1/37 (2.7%)
    Spondylitis 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Spondylolisthesis 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Tendon disorder 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Tendon pain 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Tendonitis 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Trigger finger 1/197 (0.5%) 1/198 (0.5%) 0/37 (0%)
    Vertebral foraminal stenosis 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Arthritis 3/197 (1.5%) 4/198 (2%) 1/37 (2.7%)
    Inguinal mass 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Benign salivary gland neoplasm 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Bladder neoplasm 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Cancer pain 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Colon adenoma 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Colon cancer 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Basal cell carcinoma 5/197 (2.5%) 1/198 (0.5%) 0/37 (0%)
    Lipoma 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Lung adenocarcinoma 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Metastases to bone 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Plasma cell myeloma 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Renal oncocytoma 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Seborrhoeic keratosis 1/197 (0.5%) 1/198 (0.5%) 0/37 (0%)
    Skin papilloma 2/197 (1%) 0/198 (0%) 0/37 (0%)
    Small cell lung cancer 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Squamous cell carcinoma of skin 2/197 (1%) 2/198 (1%) 0/37 (0%)
    Thyroid neoplasm 0/197 (0%) 0/198 (0%) 1/37 (2.7%)
    Tumour pain 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Nervous system disorders
    Dizziness 26/197 (13.2%) 15/198 (7.6%) 6/37 (16.2%)
    Headache 14/197 (7.1%) 15/198 (7.6%) 1/37 (2.7%)
    Altered state of consciousness 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Amnesia 7/197 (3.6%) 0/198 (0%) 3/37 (8.1%)
    Aphasia 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Ataxia 2/197 (1%) 0/198 (0%) 0/37 (0%)
    Balance disorder 3/197 (1.5%) 1/198 (0.5%) 2/37 (5.4%)
    Carotid artery occlusion 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Carpal tunnel syndrome 1/197 (0.5%) 1/198 (0.5%) 0/37 (0%)
    Cerebellar infarction 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Cerebrovascular accident 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Cervical radiculopathy 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Cognitive disorder 2/197 (1%) 0/198 (0%) 1/37 (2.7%)
    Dementia 2/197 (1%) 0/198 (0%) 0/37 (0%)
    Depressed level of consciousness 1/197 (0.5%) 1/198 (0.5%) 0/37 (0%)
    Diabetic neuropathy 0/197 (0%) 0/198 (0%) 1/37 (2.7%)
    Disturbance in attention 2/197 (1%) 0/198 (0%) 0/37 (0%)
    Dysaesthesia 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Dysarthria 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Dysgeusia 8/197 (4.1%) 3/198 (1.5%) 1/37 (2.7%)
    Encephalopathy 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Essential tremor 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Hemiparesis 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Hypersomnia 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Hypoaesthesia 4/197 (2%) 3/198 (1.5%) 0/37 (0%)
    Hypogeusia 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Hyposmia 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Lethargy 2/197 (1%) 0/198 (0%) 0/37 (0%)
    Memory impairment 8/197 (4.1%) 3/198 (1.5%) 0/37 (0%)
    Migraine 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Neuropathy peripheral 7/197 (3.6%) 0/198 (0%) 2/37 (5.4%)
    Paraesthesia 8/197 (4.1%) 4/198 (2%) 0/37 (0%)
    Parkinson's disease 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Parosmia 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Peripheral sensory neuropathy 2/197 (1%) 0/198 (0%) 1/37 (2.7%)
    Peroneal nerve palsy 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Presyncope 5/197 (2.5%) 1/198 (0.5%) 0/37 (0%)
    Restless legs syndrome 2/197 (1%) 0/198 (0%) 0/37 (0%)
    Sciatica 3/197 (1.5%) 2/198 (1%) 0/37 (0%)
    Transient ischaemic attack 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Tremor 3/197 (1.5%) 1/198 (0.5%) 0/37 (0%)
    VIIth nerve paralysis 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Visual field defect 1/197 (0.5%) 1/198 (0.5%) 0/37 (0%)
    Vocal cord paralysis 1/197 (0.5%) 1/198 (0.5%) 0/37 (0%)
    Muscle spasticity 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Periodic limb movement disorder 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Post-traumatic headache 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Syncope 7/197 (3.6%) 3/198 (1.5%) 1/37 (2.7%)
    Psychiatric disorders
    Anxiety 13/197 (6.6%) 3/198 (1.5%) 0/37 (0%)
    Depression 15/197 (7.6%) 8/198 (4%) 2/37 (5.4%)
    Insomnia 22/197 (11.2%) 9/198 (4.5%) 2/37 (5.4%)
    Abnormal dreams 2/197 (1%) 1/198 (0.5%) 0/37 (0%)
    Agitation 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Alcoholism 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Apathy 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Confusional state 6/197 (3%) 2/198 (1%) 0/37 (0%)
    Delirium 1/197 (0.5%) 2/198 (1%) 0/37 (0%)
    Depressed mood 0/197 (0%) 2/198 (1%) 0/37 (0%)
    Disorientation 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Emotional distress 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Hallucination 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Libido decreased 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Mental status changes 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Mood altered 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Mood swings 2/197 (1%) 0/198 (0%) 0/37 (0%)
    Nervousness 3/197 (1.5%) 0/198 (0%) 0/37 (0%)
    Personality change 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Restlessness 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Sleep disorder 3/197 (1.5%) 0/198 (0%) 0/37 (0%)
    Sleep terror 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Suicidal ideation 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Renal and urinary disorders
    Haematuria 16/197 (8.1%) 13/198 (6.6%) 3/37 (8.1%)
    Renal failure acute 7/197 (3.6%) 12/198 (6.1%) 1/37 (2.7%)
    Bladder neck obstruction 1/197 (0.5%) 0/198 (0%) 1/37 (2.7%)
    Bladder outlet obstruction 2/197 (1%) 0/198 (0%) 0/37 (0%)
    Bladder spasm 1/197 (0.5%) 3/198 (1.5%) 0/37 (0%)
    Calculus bladder 2/197 (1%) 1/198 (0.5%) 0/37 (0%)
    Chromaturia 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Cystitis noninfective 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Dysuria 2/197 (1%) 7/198 (3.5%) 0/37 (0%)
    Enuresis 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Haemorrhage urinary tract 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Hydronephrosis 6/197 (3%) 8/198 (4%) 1/37 (2.7%)
    Hypertonic bladder 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Incontinence 2/197 (1%) 0/198 (0%) 0/37 (0%)
    Microalbuminuria 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Micturition urgency 9/197 (4.6%) 1/198 (0.5%) 0/37 (0%)
    Nephrolithiasis 3/197 (1.5%) 1/198 (0.5%) 0/37 (0%)
    Nocturia 3/197 (1.5%) 4/198 (2%) 2/37 (5.4%)
    Oliguria 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Pneumaturia 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Pollakiuria 11/197 (5.6%) 7/198 (3.5%) 0/37 (0%)
    Proteinuria 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Pyuria 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Renal cyst 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Renal failure 1/197 (0.5%) 3/198 (1.5%) 0/37 (0%)
    Renal failure chronic 3/197 (1.5%) 1/198 (0.5%) 1/37 (2.7%)
    Renal impairment 0/197 (0%) 2/198 (1%) 0/37 (0%)
    Renal pain 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Stress urinary incontinence 1/197 (0.5%) 1/198 (0.5%) 0/37 (0%)
    Urethral haemorrhage 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Urethral stenosis 0/197 (0%) 2/198 (1%) 0/37 (0%)
    Urethritis noninfective 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Urge incontinence 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Urinary hesitation 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Urinary incontinence 10/197 (5.1%) 8/198 (4%) 1/37 (2.7%)
    Urinary retention 5/197 (2.5%) 7/198 (3.5%) 0/37 (0%)
    Urinary tract obstruction 3/197 (1.5%) 3/198 (1.5%) 0/37 (0%)
    Urine flow decreased 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Reproductive system and breast disorders
    Balanoposthitis 1/197 (0.5%) 1/198 (0.5%) 0/37 (0%)
    Benign prostatic hyperplasia 1/197 (0.5%) 1/198 (0.5%) 0/37 (0%)
    Breast pain 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Breast tenderness 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Erectile dysfunction 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Genital discomfort 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Genital lesion 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Genital rash 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Gynaecomastia 2/197 (1%) 2/198 (1%) 0/37 (0%)
    Nipple pain 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Pelvic pain 1/197 (0.5%) 1/198 (0.5%) 0/37 (0%)
    Penile oedema 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Penile swelling 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Priapism 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Prostatic pain 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Prostatitis 0/197 (0%) 0/198 (0%) 1/37 (2.7%)
    Prostatomegaly 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Scrotal swelling 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Testicular pain 4/197 (2%) 0/198 (0%) 0/37 (0%)
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea 19/197 (9.6%) 12/198 (6.1%) 1/37 (2.7%)
    Acute respiratory failure 2/197 (1%) 0/198 (0%) 0/37 (0%)
    Alveolar lung disease 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Aspiration 0/197 (0%) 0/198 (0%) 1/37 (2.7%)
    Atelectasis 1/197 (0.5%) 2/198 (1%) 1/37 (2.7%)
    Chronic obstructive pulmonary disease 2/197 (1%) 1/198 (0.5%) 0/37 (0%)
    Cough 14/197 (7.1%) 9/198 (4.5%) 1/37 (2.7%)
    Dysphonia 5/197 (2.5%) 0/198 (0%) 0/37 (0%)
    Dyspnoea exertional 5/197 (2.5%) 2/198 (1%) 0/37 (0%)
    Dyspnoea paroxysmal nocturnal 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Emphysema 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Epistaxis 3/197 (1.5%) 1/198 (0.5%) 0/37 (0%)
    Hiccups 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Hypoxia 0/197 (0%) 2/198 (1%) 0/37 (0%)
    Increased upper airway secretion 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Nasal congestion 4/197 (2%) 3/198 (1.5%) 0/37 (0%)
    Nasal dryness 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Oropharyngeal pain 6/197 (3%) 1/198 (0.5%) 0/37 (0%)
    Pleural effusion 2/197 (1%) 2/198 (1%) 0/37 (0%)
    Pneumonia aspiration 0/197 (0%) 2/198 (1%) 0/37 (0%)
    Pneumothorax 1/197 (0.5%) 1/198 (0.5%) 0/37 (0%)
    Productive cough 5/197 (2.5%) 2/198 (1%) 0/37 (0%)
    Pulmonary fibrosis 0/197 (0%) 0/198 (0%) 1/37 (2.7%)
    Pulmonary hypertension 2/197 (1%) 0/198 (0%) 0/37 (0%)
    Pulmonary vascular disorder 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Rales 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Respiratory disorder 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Respiratory failure 0/197 (0%) 2/198 (1%) 0/37 (0%)
    Respiratory tract congestion 2/197 (1%) 1/198 (0.5%) 0/37 (0%)
    Rhinitis allergic 2/197 (1%) 1/198 (0.5%) 0/37 (0%)
    Rhinorrhoea 3/197 (1.5%) 1/198 (0.5%) 0/37 (0%)
    Rhonchi 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Sinus congestion 2/197 (1%) 0/198 (0%) 0/37 (0%)
    Sinus disorder 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Sleep apnoea syndrome 5/197 (2.5%) 0/198 (0%) 0/37 (0%)
    Throat irritation 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Upper-airway cough syndrome 4/197 (2%) 0/198 (0%) 0/37 (0%)
    Wheezing 2/197 (1%) 2/198 (1%) 0/37 (0%)
    Skin and subcutaneous tissue disorders
    Rash 12/197 (6.1%) 9/198 (4.5%) 3/37 (8.1%)
    Actinic keratosis 3/197 (1.5%) 2/198 (1%) 0/37 (0%)
    Alopecia 4/197 (2%) 2/198 (1%) 0/37 (0%)
    Blister 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Decubitus ulcer 0/197 (0%) 2/198 (1%) 0/37 (0%)
    Dermatitis allergic 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Dermatitis contact 1/197 (0.5%) 1/198 (0.5%) 0/37 (0%)
    Diabetic foot 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Dry skin 5/197 (2.5%) 3/198 (1.5%) 0/37 (0%)
    Ecchymosis 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Eczema 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Erythema 3/197 (1.5%) 1/198 (0.5%) 0/37 (0%)
    Hair growth abnormal 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Hyperhidrosis 7/197 (3.6%) 2/198 (1%) 0/37 (0%)
    Hyperkeratosis 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Ingrowing nail 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Lentigo 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Night sweats 1/197 (0.5%) 2/198 (1%) 0/37 (0%)
    Pain of skin 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Photodermatosis 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Pigmentation disorder 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Pruritus 5/197 (2.5%) 3/198 (1.5%) 1/37 (2.7%)
    Psoriasis 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Rash generalised 0/197 (0%) 0/198 (0%) 1/37 (2.7%)
    Rash macular 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Rash maculo-papular 2/197 (1%) 0/198 (0%) 0/37 (0%)
    Rash pruritic 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Skin discolouration 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Skin disorder 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Skin hypopigmentation 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Skin lesion 1/197 (0.5%) 1/198 (0.5%) 0/37 (0%)
    Skin ulcer 2/197 (1%) 1/198 (0.5%) 1/37 (2.7%)
    Swelling face 2/197 (1%) 0/198 (0%) 0/37 (0%)
    Surgical and medical procedures
    Cataract operation 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Skin neoplasm excision 0/197 (0%) 1/198 (0.5%) 1/37 (2.7%)
    Vascular disorders
    Hot flush 34/197 (17.3%) 20/198 (10.1%) 2/37 (5.4%)
    Hypertension 25/197 (12.7%) 10/198 (5.1%) 5/37 (13.5%)
    Accelerated hypertension 1/197 (0.5%) 1/198 (0.5%) 0/37 (0%)
    Aortic arteriosclerosis 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Arteriovenous fistula 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Blood pressure inadequately controlled 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Deep vein thrombosis 3/197 (1.5%) 1/198 (0.5%) 1/37 (2.7%)
    Flushing 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Haematoma 1/197 (0.5%) 1/198 (0.5%) 1/37 (2.7%)
    Hypotension 4/197 (2%) 5/198 (2.5%) 4/37 (10.8%)
    Intermittent claudication 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Jugular vein thrombosis 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Orthostatic hypotension 2/197 (1%) 2/198 (1%) 1/37 (2.7%)
    Peripheral arterial occlusive disease 2/197 (1%) 0/198 (0%) 0/37 (0%)
    Peripheral artery stenosis 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Peripheral coldness 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Peripheral ischaemia 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Peripheral vascular disorder 1/197 (0.5%) 2/198 (1%) 0/37 (0%)
    Thrombophlebitis superficial 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Thrombosis 1/197 (0.5%) 0/198 (0%) 0/37 (0%)
    Varicose vein 0/197 (0%) 1/198 (0.5%) 0/37 (0%)
    Aortic aneurysm 1/197 (0.5%) 0/198 (0%) 1/37 (2.7%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

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

    PI agrees not to independently publish the results before the publication of the multi-center PI paper. Sponsor shall review and comment 30 days prior to submission or disclosure. If publication or disclosure contains Sponsor Confidential Information, other than study data, PI agrees to remove Confidential Information from publication or disclosure. Sponsor may request that PI delay such publication for an additional 60 days to protect the patentability of any invention described.

    Results Point of Contact

    Name/Title Pfizer ClinicalTrials.gov Call Center
    Organization Pfizer Inc.
    Phone 1-800-718-1021
    Email ClinicalTrials.gov_Inquiries@pfizer.com
    Responsible Party:
    Pfizer
    ClinicalTrials.gov Identifier:
    NCT01664923
    Other Study ID Numbers:
    • MDV3100-09
    • C3431014
    First Posted:
    Aug 14, 2012
    Last Update Posted:
    Jan 30, 2019
    Last Verified:
    Jan 1, 2019