An Efficacy and Safety Study of Apalutamide (JNJ-56021927) in Combination With Abiraterone Acetate and Prednisone Versus Abiraterone Acetate and Prednisone in Participants With Chemotherapy-naive Metastatic Castration-resistant Prostate Cancer (mCRPC)

Sponsor
Aragon Pharmaceuticals, Inc. (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT02257736
Collaborator
(none)
982
184
2
100.3
5.3
0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to compare the radiographic progression-free survival (rPFS) of apalutamide in combination with abiraterone acetate (AA) plus prednisone or prednisolone (AAP) and AAP in participants with chemotherapy-naive (participants who did not receive any chemotherapy [treatment of cancer using drugs]) metastatic castration-resistant prostate cancer (mCRPC) (cancer of prostate gland [gland that makes fluid that aids movement of sperm]).

Condition or Disease Intervention/Treatment Phase
Phase 3

Detailed Description

This is a randomized (study drug assigned by chance), double-blind (neither the Investigator nor the participant know the treatment) placebo-controlled and multicenter (when more than 1 hospital or medical school team work on a medical research study) study to determine if participants with chemotherapy-naive mCRPC will benefit from the addition of apalutamide to AAP compared with AAP alone. The study consists of 3 phases: Screening phase; Treatment phase, and Follow-up phase. At the final analysis, the study will be unblinded. After the Independent Data Monitoring Committee (IDMC) review and the sponsor's subsequent decision participants will be offered to receive treatment either in the Open-Label Extension Phase or the Long-Term Extension Phase of study. Participants' safety will be monitored throughout the study.

Study Design

Study Type:
Interventional
Actual Enrollment :
982 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
A Phase 3 Randomized, Placebo-controlled Double-blind Study of JNJ-56021927 in Combination With Abiraterone Acetate and Prednisone Versus Abiraterone Acetate and Prednisone in Subjects With Chemotherapy-naive Metastatic Castration-resistant Prostate Cancer (mCRPC)
Actual Study Start Date :
Nov 26, 2014
Actual Primary Completion Date :
Mar 19, 2018
Anticipated Study Completion Date :
Apr 5, 2023

Arms and Interventions

Arm Intervention/Treatment
Experimental: Group 1: AAP and apalutamide

Participants will receive apalutamide 240 milligram (mg) (4*60 mg tablets) and abiraterone acetate (AA) 1000 mg (4*250 mg tablets) once daily on an empty stomach and 5 mg prednisone (P), AAP, twice daily, until disease progression, unacceptable toxicity or end of treatment, whichever occurs first. After unblinding participants will be offered further treatment as defined in the Open-Label Extension (OLE) or Long-Term Extension (LTE) phase (AAP + open label apalutamide or AAP alone).

Drug: Apalutamide
Participants will receive 240 mg (4*60 mg tablets) of apalutamide once daily orally.

Drug: Abiraterone acetate
Participants will receive 1000 mg (4*250 mg tablets) of abiraterone acetate (AA) once daily orally.
Other Names:
  • ZYTIGA
  • Drug: Prednisone
    Participants will receive 5 mg tablet of prednisone twice daily orally.

    Placebo Comparator: Group 2: AAP and Placebo

    Participants will receive matching Placebo of apalutamide and abiraterone acetate (AA) 1000 mg (4*250 mg tablets) once daily on an empty stomach and 5 mg prednisone (P), AAP, twice daily until disease progression, unacceptable toxicity or end of treatment, whichever occurs first. After unblinding participants will be offered further treatment as defined in the OLE or LTE phase (AAP + open label apalutamide or AAP alone).

    Drug: Abiraterone acetate
    Participants will receive 1000 mg (4*250 mg tablets) of abiraterone acetate (AA) once daily orally.
    Other Names:
  • ZYTIGA
  • Drug: Prednisone
    Participants will receive 5 mg tablet of prednisone twice daily orally.

    Drug: Placebo
    Participants will receive matching placebo to apalutamide once daily orally.

    Outcome Measures

    Primary Outcome Measures

    1. Radiographic Progression-free Survival (rPFS) [Up to 3 years and 4 months]

      The rPFS was defined as the time from randomization to the occurrence of one of the following: 1) a participant was considered to have progressed by bone scan if - a) the first bone scan with greater than or equal to (>=) 2 new lesions compared to baseline was observed in less than (<) 12 weeks from randomization and was confirmed by a second bone scan taken >=6 weeks later showing >=2 additional new lesions (a total of >=4 new lesions compared to baseline), b) the first bone scan with >=2 new lesions compared to baseline was observed in >=12 weeks from randomization and the new lesions were verified on the next bone scan >=6 weeks later (a total of >=2 new lesions compared to baseline); 2) progression of soft tissue lesions measured by computerized tomography (CT) or magnetic resonance imaging (MRI) as per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1.

    Secondary Outcome Measures

    1. Overall Survival (OS) [Up to 5 years and 10 months]

      The OS was defined as the time from randomization to date of death from any cause.

    2. Time to Chronic Opioid Use [Up to 5 years and 10 months]

      Time to chronic opioid use was defined as the time from date of randomization to the first date of opioid use.

    3. Time to Initiation of Cytotoxic Chemotherapy [Up to 5 years and 10 months]

      Time to initiation of cytotoxic chemotherapy was defined as the time from date of randomization to the date of initiation of cytotoxic chemotherapy.

    4. Time to Pain Progression [Up to 5 years and 10 months]

      Time to pain progression: time from randomization to first date that participant either experienced an increase by 2 points from baseline in Brief Pain Inventory Short Form (BPI-SF) worst pain intensity item (item 3) or Case Report Form (CRF) pain, observed at 2 consecutive evaluations >=4 wks apart, or initiation of chronic opioids as defined in time to chronic opioid use, whichever occurred first. BPI-SF is a self-administered questionnaire developed to assess severity of pain and impact of pain on daily functions. Item 3(worst pain intensity) asks participants to rate worst pain in prior 7-days on a 0-10 numeric rating scale, where "0" indicates "No pain" and "10" indicates "Pain as bad as you can imagine." A lower score is better.CRF pain refers to participant's response to global pain assessment "How would you rate your pain over the past 7 days?"with a scale of 0("No pain") to 10("Pain as bad as you can imagine"),that is systematically reported and recorded on the eCRF.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    Male
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Adenocarcinoma of the prostate

    • Metastatic disease as documented by technetium-99m (99mTc) bone scan or metastatic lesions by computed tomography (CT) or magnetic resonance imaging (MRI) scans (visceral or lymph node disease). If lymph node metastasis is the only evidence of metastasis, it must be greater than or equal to (>=) 2 centimeter (cm) in the longest diameter

    • Castration-resistant prostate cancer demonstrated during continuous androgen deprivation therapy (ADT), defined as 3 rises of PSA, at least 1 week apart with the last androgen deprivation therapy (PSA) >= 2 nanogram per milliliters (ng/mL)

    • Participants who received a first generation anti-androgen (eg, bicalutamide, flutamide, nilutamide) must have at least a 6-week washout prior to randomization and must show continuing disease (PSA) progression (an increase in PSA) after the washout period

    • Prostate cancer progression documented by prostate-specific antigen (PSA) according to the Prostate Cancer Clinical Trials Working Group (PCWG2) or radiographic progression of soft tissue according to modified Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST) modified based on PCWG2, or radiographic progression of bone according to PCWG2

    • Participants who cross-over from Prednisone alone to open-label apalutamide plus AAP should still be in the double-blind phase of the study, should be receiving AAP alone and should have ECOG 0-1-2.

    Exclusion Criteria:
    • Small cell or neuroendocrine carcinoma of the prostate

    • Known brain metastases

    • Prior chemotherapy for prostate cancer, except if administered in the adjuvant/neoadjuvant setting

    • Previously treated with ketoconazole for prostate cancer for greater than 7 days

    • Therapies that must be discontinued or substituted at least 4 weeks prior to randomization include the following: a) Medications known to lower the seizure threshold, b) Herbal and non-herbal products that may decrease PSA levels (example [eg], saw palmetto, pomegranate) or c) Any investigational agent

    • At Screening need for parenteral or oral opioid analgesics (eg, codeine, dextropropoxyphene)

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Phoenix Arizona United States
    2 La Mesa California United States
    3 Los Angeles California United States
    4 Modesto California United States
    5 San Diego California United States
    6 San Francisco California United States
    7 Santa Barbara California United States
    8 Aurora Colorado United States
    9 Denver Colorado United States
    10 New Haven Connecticut United States
    11 Jensen Beach Florida United States
    12 Lakeland Florida United States
    13 New Port Richey Florida United States
    14 Ocala Florida United States
    15 Atlanta Georgia United States
    16 Melrose Illinois United States
    17 Niles Illinois United States
    18 Marrero Louisiana United States
    19 New Orleans Louisiana United States
    20 Shreveport Louisiana United States
    21 Auburn Maine United States
    22 Baltimore Maryland United States
    23 Boston Massachusetts United States
    24 Saint Louis Missouri United States
    25 Omaha Nebraska United States
    26 Las Vegas Nevada United States
    27 Albany New York United States
    28 Bronx New York United States
    29 Johnson City New York United States
    30 New York New York United States
    31 Poughkeepsie New York United States
    32 Syracuse New York United States
    33 Columbus Ohio United States
    34 Tualatin Oregon United States
    35 Lancaster Pennsylvania United States
    36 Pittsburgh Pennsylvania United States
    37 Charleston South Carolina United States
    38 Myrtle Beach South Carolina United States
    39 Nashville Tennessee United States
    40 Austin Texas United States
    41 Houston Texas United States
    42 Norfolk Virginia United States
    43 Richmond Virginia United States
    44 Auburn Washington United States
    45 Seattle Washington United States
    46 Spokane Washington United States
    47 Wenatchee Washington United States
    48 Madison Wisconsin United States
    49 Ciudad Automoma Buenos Aires Argentina
    50 Ciudad de Buenos Aires Argentina
    51 Cordoba Argentina
    52 La Rioja Argentina
    53 Mendoza Argentina
    54 Rosario Argentina
    55 Adelaide Australia
    56 Ashford Australia
    57 Camperdown Australia
    58 Herston Australia
    59 Liverpool Australia
    60 Malvern Australia
    61 Melbourne Australia
    62 Southport Australia
    63 Wahroonga Australia
    64 West Heidelberg Australia
    65 Woolloongabba Australia
    66 Antwerpen Belgium
    67 Bruxelles Belgium
    68 Gent Belgium
    69 Gosselies Belgium
    70 Leuven Belgium
    71 Liege Belgium
    72 Namur Belgium
    73 Ottignies Belgium
    74 Roeselare Belgium
    75 Sint-Niklaas Belgium
    76 Barretos Brazil
    77 IjuĂ­ Brazil
    78 Natal Brazil
    79 Porto Alegre Brazil
    80 Sao Jose Do Rio Preto Brazil
    81 Sao Paulo Brazil
    82 Abbotsford British Columbia Canada
    83 Kelowna British Columbia Canada
    84 Vancouver British Columbia Canada
    85 Halifax Nova Scotia Canada
    86 Barrie Ontario Canada
    87 London Ontario Canada
    88 Oakville Ontario Canada
    89 Toronto Ontario Canada
    90 Weston Ontario Canada
    91 Montreal Quebec Canada
    92 Sherbrooke Quebec Canada
    93 Quebec Canada
    94 Toronto Canada
    95 Angers Cedex 9 France
    96 Caen Cedex 05 France
    97 Dijon Cedex France
    98 Le Mans Cedex 2 France
    99 Lyon cedex 03 France
    100 Lyon France
    101 Montpellier France
    102 Paris Cedex 15 France
    103 Saint Herblain France
    104 Toulouse Cedex 9 France
    105 Berlin Germany
    106 Braunschweig Germany
    107 Dresden Germany
    108 Frankfurt Germany
    109 Freiburg Germany
    110 Hamburg Germany
    111 Heidelberg Germany
    112 Muenchen Germany
    113 Muenster Germany
    114 Nuertingen Germany
    115 TĂĽbingen Germany
    116 Wuppertal Germany
    117 Fukuoka-shi Japan
    118 Kanazawa Japan
    119 Kashiwa Japan
    120 Kita-Gun Japan
    121 Kumamoto Japan
    122 Kurume Japan
    123 Matsuyama-Shi Japan
    124 Miyazaki Japan
    125 Nagasaki Japan
    126 Osaka-Sayama Japan
    127 Osaka Japan
    128 Sakura Japan
    129 Sapporo Japan
    130 Ube Japan
    131 Yokohama Japan
    132 Goyang-Si Korea, Republic of
    133 Seongnam Korea, Republic of
    134 Seoul Korea, Republic of
    135 Chihuahua Mexico
    136 Cuernavaca Mexico
    137 Culiacan Mexico
    138 Mexico Mexico
    139 Oaxaca Mexico
    140 Zapopan Mexico
    141 Amsterdam Zuidoost Netherlands
    142 Amsterdam Netherlands
    143 Blaricum Netherlands
    144 Den Haag Netherlands
    145 Dordrecht Netherlands
    146 Groningen Netherlands
    147 Heerlen Netherlands
    148 Nieuwegein Netherlands
    149 Nijmegen Netherlands
    150 Rotterdam Netherlands
    151 Kursk Russian Federation
    152 Moscow Russian Federation
    153 Omsk Russian Federation
    154 Pyatigorsk Russian Federation
    155 Rostov-on-Don Russian Federation
    156 Saint Petersburg Russian Federation
    157 Saint-Petersburg, Russian Federation
    158 Saint-Petersburg Russian Federation
    159 Ufa Russian Federation
    160 Bloemfontein South Africa
    161 Cape Town South Africa
    162 Johannesburg South Africa
    163 Pretoria South Africa
    164 Alcorcon Spain
    165 Barcelona Spain
    166 Cadiz Spain
    167 Cordoba Spain
    168 Madrid Spain
    169 San Sebastián de los Reyes Spain
    170 Valencia Spain
    171 Ayr United Kingdom
    172 Belfast United Kingdom
    173 Birmingham United Kingdom
    174 Bristol United Kingdom
    175 Edinburgh United Kingdom
    176 Glasgow United Kingdom
    177 London United Kingdom
    178 Manchester United Kingdom
    179 Plymouth United Kingdom
    180 Preston United Kingdom
    181 Stevenage United Kingdom
    182 Sutton United Kingdom
    183 Westcliff on Sea United Kingdom
    184 Wirral United Kingdom

    Sponsors and Collaborators

    • Aragon Pharmaceuticals, Inc.

    Investigators

    • Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Aragon Pharmaceuticals, Inc.
    ClinicalTrials.gov Identifier:
    NCT02257736
    Other Study ID Numbers:
    • CR105505
    • 56021927PCR3001
    • 2014-001718-25
    First Posted:
    Oct 6, 2014
    Last Update Posted:
    Aug 4, 2022
    Last Verified:
    Aug 1, 2022
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Keywords provided by Aragon Pharmaceuticals, Inc.
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail Treatment disposition has been reported in participant flow.
    Arm/Group Title Placebo+ Abiraterone Acetate - Prednisolone Apalutamide + Abiraterone Acetate - Prednisolone
    Arm/Group Description Participants received 4*60 milligrams (mg) tablets of matching placebo orally once daily (qd) with or without food and 4*250 mg tablets of abiraterone acetate (AA) orally qd on empty stomach followed by prednisolone 5 mg orally twice daily with food for 24 cycles (each cycle was equal to 28 days), and thereafter every 3 cycles. Participants received treatment until radiographic progression or unequivocal clinical progression, unacceptable toxicity, or death. Participants received 4*60 mg tablets of apalutamide tablets orally qd with or without food and 4*250 mg tablets of AA orally qd on empty stomach followed by prednisolone 5 mg orally twice daily with food for 24 cycles, and thereafter every 3 cycles. Participants received treatment until radiographic progression or unequivocal clinical progression, unacceptable toxicity, or death.
    Period Title: Overall Study
    STARTED 490 492
    COMPLETED 39 45
    NOT COMPLETED 451 447

    Baseline Characteristics

    Arm/Group Title Placebo+ Abiraterone Acetate - Prednisolone Apalutamide + Abiraterone Acetate - Prednisolone Total
    Arm/Group Description Participants received 4*60 milligrams (mg) tablets of matching placebo orally once daily (qd) with or without food and 4*250 mg tablets of abiraterone acetate (AA) orally qd on empty stomach followed by prednisolone 5 mg orally twice daily with food for 24 cycles (each cycle was equal to 28 days), and thereafter every 3 cycles. Participants received treatment until radiographic progression or unequivocal clinical progression, unacceptable toxicity, or death. Participants received 4*60 mg tablets of apalutamide tablets orally qd with or without food and 4*250 mg tablets of AA orally qd on empty stomach followed by prednisolone 5 mg orally twice daily with food for 24 cycles, and thereafter every 3 cycles. Participants received treatment until radiographic progression or unequivocal clinical progression, unacceptable toxicity, or death. Total of all reporting groups
    Overall Participants 490 492 982
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    70.7
    (8.06)
    71.4
    (8.34)
    71.1
    (8.21)
    Sex: Female, Male (Count of Participants)
    Female
    0
    0%
    0
    0%
    0
    0%
    Male
    490
    100%
    492
    100%
    982
    100%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    54
    11%
    50
    10.2%
    104
    10.6%
    Not Hispanic or Latino
    411
    83.9%
    422
    85.8%
    833
    84.8%
    Unknown or Not Reported
    25
    5.1%
    20
    4.1%
    45
    4.6%
    Race/Ethnicity, Customized (Count of Participants)
    American Indian or Alaska Native
    8
    1.6%
    9
    1.8%
    17
    1.7%
    Asian
    53
    10.8%
    58
    11.8%
    111
    11.3%
    Black or African American
    18
    3.7%
    19
    3.9%
    37
    3.8%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    White
    373
    76.1%
    365
    74.2%
    738
    75.2%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    20
    4.1%
    20
    4.1%
    40
    4.1%
    Other
    18
    3.7%
    21
    4.3%
    39
    4%
    Region of Enrollment (Count of Participants)
    ARGENTINA
    3
    0.6%
    3
    0.6%
    6
    0.6%
    AUSTRALIA
    31
    6.3%
    47
    9.6%
    78
    7.9%
    BELGIUM
    16
    3.3%
    16
    3.3%
    32
    3.3%
    BRAZIL
    21
    4.3%
    18
    3.7%
    39
    4%
    CANADA
    12
    2.4%
    18
    3.7%
    30
    3.1%
    FRANCE
    18
    3.7%
    16
    3.3%
    34
    3.5%
    GERMANY
    10
    2%
    9
    1.8%
    19
    1.9%
    ITALY
    33
    6.7%
    36
    7.3%
    69
    7%
    JAPAN
    23
    4.7%
    27
    5.5%
    50
    5.1%
    MEXICO
    19
    3.9%
    16
    3.3%
    35
    3.6%
    NETHERLANDS
    14
    2.9%
    16
    3.3%
    30
    3.1%
    RUSSIAN FEDERATION
    59
    12%
    46
    9.3%
    105
    10.7%
    SOUTH AFRICA
    9
    1.8%
    8
    1.6%
    17
    1.7%
    SOUTH KOREA
    28
    5.7%
    29
    5.9%
    57
    5.8%
    SPAIN
    43
    8.8%
    36
    7.3%
    79
    8%
    UNITED KINGDOM
    23
    4.7%
    27
    5.5%
    50
    5.1%
    UNITED STATES
    128
    26.1%
    124
    25.2%
    252
    25.7%

    Outcome Measures

    1. Primary Outcome
    Title Radiographic Progression-free Survival (rPFS)
    Description The rPFS was defined as the time from randomization to the occurrence of one of the following: 1) a participant was considered to have progressed by bone scan if - a) the first bone scan with greater than or equal to (>=) 2 new lesions compared to baseline was observed in less than (<) 12 weeks from randomization and was confirmed by a second bone scan taken >=6 weeks later showing >=2 additional new lesions (a total of >=4 new lesions compared to baseline), b) the first bone scan with >=2 new lesions compared to baseline was observed in >=12 weeks from randomization and the new lesions were verified on the next bone scan >=6 weeks later (a total of >=2 new lesions compared to baseline); 2) progression of soft tissue lesions measured by computerized tomography (CT) or magnetic resonance imaging (MRI) as per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1.
    Time Frame Up to 3 years and 4 months

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat (ITT) population included all randomized participants who were classified according to their assigned treatment group, regardless of the actual treatment received.
    Arm/Group Title Placebo+ Abiraterone Acetate - Prednisolone Apalutamide + Abiraterone Acetate - Prednisolone
    Arm/Group Description Participants received 4*60 milligrams (mg) tablets of matching placebo orally once daily (qd) with or without food and 4*250 mg tablets of abiraterone acetate (AA) orally qd on empty stomach followed by prednisolone 5 mg orally twice daily with food for 24 cycles (each cycle was equal to 28 days), and thereafter every 3 cycles. Participants received treatment until radiographic progression or unequivocal clinical progression, unacceptable toxicity, or death. Participants received 4*60 mg tablets of apalutamide tablets orally qd with or without food and 4*250 mg tablets of AA orally qd on empty stomach followed by prednisolone 5 mg orally twice daily with food for 24 cycles, and thereafter every 3 cycles. Participants received treatment until radiographic progression or unequivocal clinical progression, unacceptable toxicity, or death.
    Measure Participants 490 492
    Median (95% Confidence Interval) [months]
    16.59
    23.98
    2. Secondary Outcome
    Title Overall Survival (OS)
    Description The OS was defined as the time from randomization to date of death from any cause.
    Time Frame Up to 5 years and 10 months

    Outcome Measure Data

    Analysis Population Description
    ITT population included all randomized participants who were classified according to their assigned treatment group, regardless of the actual treatment received.
    Arm/Group Title Placebo+ Abiraterone Acetate - Prednisolone Apalutamide + Abiraterone Acetate - Prednisolone
    Arm/Group Description Participants received 4*60 milligrams (mg) tablets of matching placebo orally once daily (qd) with or without food and 4*250 mg tablets of abiraterone acetate (AA) orally qd on empty stomach followed by prednisolone 5 mg orally twice daily with food for 24 cycles (each cycle was equal to 28 days), and thereafter every 3 cycles. Participants received treatment until radiographic progression or unequivocal clinical progression, unacceptable toxicity, or death. Participants received 4*60 mg tablets of apalutamide tablets orally qd with or without food and 4*250 mg tablets of AA orally qd on empty stomach followed by prednisolone 5 mg orally twice daily with food for 24 cycles, and thereafter every 3 cycles. Participants received treatment until radiographic progression or unequivocal clinical progression, unacceptable toxicity, or death.
    Measure Participants 490 492
    Median (95% Confidence Interval) [months]
    33.71
    36.17
    3. Secondary Outcome
    Title Time to Chronic Opioid Use
    Description Time to chronic opioid use was defined as the time from date of randomization to the first date of opioid use.
    Time Frame Up to 5 years and 10 months

    Outcome Measure Data

    Analysis Population Description
    ITT population included all randomized participants who were classified according to their assigned treatment group, regardless of the actual treatment received.
    Arm/Group Title Placebo+ Abiraterone Acetate - Prednisolone Apalutamide + Abiraterone Acetate - Prednisolone
    Arm/Group Description Participants received 4*60 milligrams (mg) tablets of matching placebo orally once daily (qd) with or without food and 4*250 mg tablets of abiraterone acetate (AA) orally qd on empty stomach followed by prednisolone 5 mg orally twice daily with food for 24 cycles (each cycle was equal to 28 days), and thereafter every 3 cycles. Participants received treatment until radiographic progression or unequivocal clinical progression, unacceptable toxicity, or death. Participants received 4*60 mg tablets of apalutamide tablets orally qd with or without food and 4*250 mg tablets of AA orally qd on empty stomach followed by prednisolone 5 mg orally twice daily with food for 24 cycles, and thereafter every 3 cycles. Participants received treatment until radiographic progression or unequivocal clinical progression, unacceptable toxicity, or death.
    Measure Participants 490 492
    Median (95% Confidence Interval) [months]
    53.26
    46.98
    4. Secondary Outcome
    Title Time to Initiation of Cytotoxic Chemotherapy
    Description Time to initiation of cytotoxic chemotherapy was defined as the time from date of randomization to the date of initiation of cytotoxic chemotherapy.
    Time Frame Up to 5 years and 10 months

    Outcome Measure Data

    Analysis Population Description
    ITT population included all randomized participants who were classified according to their assigned treatment group, regardless of the actual treatment received.
    Arm/Group Title Placebo+ Abiraterone Acetate - Prednisolone Apalutamide + Abiraterone Acetate - Prednisolone
    Arm/Group Description Participants received 4*60 milligrams (mg) tablets of matching placebo orally once daily (qd) with or without food and 4*250 mg tablets of abiraterone acetate (AA) orally qd on empty stomach followed by prednisolone 5 mg orally twice daily with food for 24 cycles (each cycle was equal to 28 days), and thereafter every 3 cycles. Participants received treatment until radiographic progression or unequivocal clinical progression, unacceptable toxicity, or death. Participants received 4*60 mg tablets of apalutamide tablets orally qd with or without food and 4*250 mg tablets of AA orally qd on empty stomach followed by prednisolone 5 mg orally twice daily with food for 24 cycles, and thereafter every 3 cycles. Participants received treatment until radiographic progression or unequivocal clinical progression, unacceptable toxicity, or death.
    Measure Participants 490 492
    Median (95% Confidence Interval) [months]
    34.23
    36.11
    5. Secondary Outcome
    Title Time to Pain Progression
    Description Time to pain progression: time from randomization to first date that participant either experienced an increase by 2 points from baseline in Brief Pain Inventory Short Form (BPI-SF) worst pain intensity item (item 3) or Case Report Form (CRF) pain, observed at 2 consecutive evaluations >=4 wks apart, or initiation of chronic opioids as defined in time to chronic opioid use, whichever occurred first. BPI-SF is a self-administered questionnaire developed to assess severity of pain and impact of pain on daily functions. Item 3(worst pain intensity) asks participants to rate worst pain in prior 7-days on a 0-10 numeric rating scale, where "0" indicates "No pain" and "10" indicates "Pain as bad as you can imagine." A lower score is better.CRF pain refers to participant's response to global pain assessment "How would you rate your pain over the past 7 days?"with a scale of 0("No pain") to 10("Pain as bad as you can imagine"),that is systematically reported and recorded on the eCRF.
    Time Frame Up to 5 years and 10 months

    Outcome Measure Data

    Analysis Population Description
    ITT population included all randomized participants who were classified according to their assigned treatment group, regardless of the actual treatment received.
    Arm/Group Title Placebo+ Abiraterone Acetate - Prednisolone Apalutamide + Abiraterone Acetate - Prednisolone
    Arm/Group Description Participants received 4*60 milligrams (mg) tablets of matching placebo orally once daily (qd) with or without food and 4*250 mg tablets of abiraterone acetate (AA) orally qd on empty stomach followed by prednisolone 5 mg orally twice daily with food for 24 cycles (each cycle was equal to 28 days), and thereafter every 3 cycles. Participants received treatment until radiographic progression or unequivocal clinical progression, unacceptable toxicity, or death. Participants received 4*60 mg tablets of apalutamide tablets orally qd with or without food and 4*250 mg tablets of AA orally qd on empty stomach followed by prednisolone 5 mg orally twice daily with food for 24 cycles, and thereafter every 3 cycles. Participants received treatment until radiographic progression or unequivocal clinical progression, unacceptable toxicity, or death.
    Measure Participants 490 492
    Median (95% Confidence Interval) [months]
    26.51
    21.82

    Adverse Events

    Time Frame Up to 3 years and 4 months
    Adverse Event Reporting Description Safety Analysis set included all participants who received at least 1 dose of study drug, with treatment assignments designated according to actual study treatment received.
    Arm/Group Title Placebo+ Abiraterone Acetate - Prednisolone Apalutamide + Abiraterone Acetate - Prednisolone
    Arm/Group Description Participants received 4*60 milligrams (mg) tablets of matching placebo orally once daily (qd) with or without food and 4*250 mg tablets of abiraterone acetate (AA) orally qd on empty stomach followed by prednisolone 5 mg orally twice daily with food for 24 cycles (each cycle was equal to 28 days), and thereafter every 3 cycles. Participants received treatment until radiographic progression or unequivocal clinical progression, unacceptable toxicity, or death. Participants received 4*60 mg tablets of apalutamide tablets orally qd with or without food and 4*250 mg tablets of AA orally qd on empty stomach followed by prednisolone 5 mg orally twice daily with food for 24 cycles, and thereafter every 3 cycles. Participants received treatment until radiographic progression or unequivocal clinical progression, unacceptable toxicity, or death.
    All Cause Mortality
    Placebo+ Abiraterone Acetate - Prednisolone Apalutamide + Abiraterone Acetate - Prednisolone
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 350/489 (71.6%) 338/490 (69%)
    Serious Adverse Events
    Placebo+ Abiraterone Acetate - Prednisolone Apalutamide + Abiraterone Acetate - Prednisolone
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 166/489 (33.9%) 192/490 (39.2%)
    Blood and lymphatic system disorders
    Anaemia 5/489 (1%) 2/490 (0.4%)
    Blood Loss Anaemia 1/489 (0.2%) 0/490 (0%)
    Disseminated Intravascular Coagulation 1/489 (0.2%) 0/490 (0%)
    Febrile Neutropenia 4/489 (0.8%) 1/490 (0.2%)
    Neutropenia 0/489 (0%) 1/490 (0.2%)
    Thrombocytopenia 1/489 (0.2%) 0/490 (0%)
    Cardiac disorders
    Acute Left Ventricular Failure 1/489 (0.2%) 0/490 (0%)
    Acute Myocardial Infarction 4/489 (0.8%) 4/490 (0.8%)
    Angina Pectoris 0/489 (0%) 4/490 (0.8%)
    Aortic Valve Incompetence 0/489 (0%) 1/490 (0.2%)
    Aortic Valve Stenosis 0/489 (0%) 1/490 (0.2%)
    Atrial Fibrillation 6/489 (1.2%) 3/490 (0.6%)
    Atrioventricular Block Complete 0/489 (0%) 1/490 (0.2%)
    Bradycardia 0/489 (0%) 2/490 (0.4%)
    Cardiac Failure 3/489 (0.6%) 2/490 (0.4%)
    Cardiac Failure Chronic 1/489 (0.2%) 0/490 (0%)
    Cardiac Failure Congestive 4/489 (0.8%) 4/490 (0.8%)
    Coronary Artery Disease 2/489 (0.4%) 1/490 (0.2%)
    Coronary Artery Stenosis 1/489 (0.2%) 0/490 (0%)
    Left Ventricular Dysfunction 0/489 (0%) 1/490 (0.2%)
    Myocardial Infarction 1/489 (0.2%) 6/490 (1.2%)
    Palpitations 0/489 (0%) 1/490 (0.2%)
    Sinus Node Dysfunction 1/489 (0.2%) 0/490 (0%)
    Stress Cardiomyopathy 0/489 (0%) 1/490 (0.2%)
    Supraventricular Tachycardia 0/489 (0%) 1/490 (0.2%)
    Ventricular Tachycardia 0/489 (0%) 2/490 (0.4%)
    Endocrine disorders
    Inappropriate Antidiuretic Hormone Secretion 1/489 (0.2%) 0/490 (0%)
    Eye disorders
    Cataract 1/489 (0.2%) 2/490 (0.4%)
    Diplopia 1/489 (0.2%) 0/490 (0%)
    Visual Impairment 0/489 (0%) 1/490 (0.2%)
    Gastrointestinal disorders
    Anal Haemorrhage 1/489 (0.2%) 0/490 (0%)
    Constipation 2/489 (0.4%) 0/490 (0%)
    Diarrhoea 1/489 (0.2%) 2/490 (0.4%)
    Diverticulum 1/489 (0.2%) 0/490 (0%)
    Diverticulum Intestinal Haemorrhagic 2/489 (0.4%) 0/490 (0%)
    Duodenal Ulcer Perforation 1/489 (0.2%) 0/490 (0%)
    Enteritis 1/489 (0.2%) 0/490 (0%)
    Food Poisoning 1/489 (0.2%) 0/490 (0%)
    Gastric Haemorrhage 1/489 (0.2%) 0/490 (0%)
    Gastritis 0/489 (0%) 1/490 (0.2%)
    Gastrointestinal Haemorrhage 3/489 (0.6%) 2/490 (0.4%)
    Haematochezia 1/489 (0.2%) 0/490 (0%)
    Inguinal Hernia 0/489 (0%) 1/490 (0.2%)
    Intestinal Obstruction 2/489 (0.4%) 3/490 (0.6%)
    Large Intestine Polyp 1/489 (0.2%) 0/490 (0%)
    Lumbar Hernia 0/489 (0%) 1/490 (0.2%)
    Melaena 1/489 (0.2%) 0/490 (0%)
    Nausea 2/489 (0.4%) 0/490 (0%)
    Pancreatitis 0/489 (0%) 1/490 (0.2%)
    Peptic Ulcer Perforation 1/489 (0.2%) 0/490 (0%)
    Periodontal Disease 1/489 (0.2%) 0/490 (0%)
    Proctitis 0/489 (0%) 1/490 (0.2%)
    Rectal Haemorrhage 5/489 (1%) 0/490 (0%)
    Small Intestinal Obstruction 0/489 (0%) 1/490 (0.2%)
    Vomiting 1/489 (0.2%) 1/490 (0.2%)
    General disorders
    Asthenia 2/489 (0.4%) 4/490 (0.8%)
    Fatigue 0/489 (0%) 1/490 (0.2%)
    Gait Inability 0/489 (0%) 1/490 (0.2%)
    General Physical Health Deterioration 3/489 (0.6%) 0/490 (0%)
    Generalised Oedema 1/489 (0.2%) 0/490 (0%)
    Granuloma 0/489 (0%) 1/490 (0.2%)
    Multiple Organ Dysfunction Syndrome 3/489 (0.6%) 0/490 (0%)
    Non-Cardiac Chest Pain 1/489 (0.2%) 5/490 (1%)
    Oedema Peripheral 2/489 (0.4%) 0/490 (0%)
    Pyrexia 4/489 (0.8%) 2/490 (0.4%)
    Systemic Inflammatory Response Syndrome 1/489 (0.2%) 0/490 (0%)
    Hepatobiliary disorders
    Bile Duct Stone 0/489 (0%) 2/490 (0.4%)
    Cholangitis 2/489 (0.4%) 0/490 (0%)
    Cholecystitis 0/489 (0%) 1/490 (0.2%)
    Cholelithiasis 1/489 (0.2%) 0/490 (0%)
    Cholestasis 1/489 (0.2%) 0/490 (0%)
    Hepatic Function Abnormal 1/489 (0.2%) 0/490 (0%)
    Immune system disorders
    Anaphylactic Reaction 0/489 (0%) 1/490 (0.2%)
    Contrast Media Allergy 0/489 (0%) 1/490 (0.2%)
    Infections and infestations
    Appendicitis 1/489 (0.2%) 0/490 (0%)
    Appendicitis Perforated 1/489 (0.2%) 0/490 (0%)
    Bacteraemia 1/489 (0.2%) 1/490 (0.2%)
    Bronchitis 1/489 (0.2%) 2/490 (0.4%)
    Catheter Site Infection 1/489 (0.2%) 0/490 (0%)
    Cellulitis 1/489 (0.2%) 1/490 (0.2%)
    Clostridium Difficile Colitis 1/489 (0.2%) 0/490 (0%)
    Diverticulitis 2/489 (0.4%) 1/490 (0.2%)
    Erysipelas 0/489 (0%) 1/490 (0.2%)
    Gangrene 1/489 (0.2%) 0/490 (0%)
    Gastroenteritis 2/489 (0.4%) 2/490 (0.4%)
    Gastroenteritis Viral 0/489 (0%) 1/490 (0.2%)
    Gastrointestinal Infection 1/489 (0.2%) 0/490 (0%)
    Herpes Zoster 0/489 (0%) 1/490 (0.2%)
    Infection 1/489 (0.2%) 0/490 (0%)
    Influenza 2/489 (0.4%) 0/490 (0%)
    Legionella Infection 0/489 (0%) 1/490 (0.2%)
    Liver Abscess 1/489 (0.2%) 0/490 (0%)
    Localised Infection 0/489 (0%) 1/490 (0.2%)
    Lower Respiratory Tract Infection 1/489 (0.2%) 2/490 (0.4%)
    Osteomyelitis 1/489 (0.2%) 2/490 (0.4%)
    Pharyngitis 0/489 (0%) 1/490 (0.2%)
    Pneumonia 10/489 (2%) 18/490 (3.7%)
    Pneumonia Klebsiella 0/489 (0%) 1/490 (0.2%)
    Pneumonia Legionella 0/489 (0%) 1/490 (0.2%)
    Post Procedural Infection 1/489 (0.2%) 0/490 (0%)
    Prostate Infection 0/489 (0%) 1/490 (0.2%)
    Pseudomembranous Colitis 1/489 (0.2%) 0/490 (0%)
    Pulmonary Mycosis 1/489 (0.2%) 0/490 (0%)
    Pulmonary Tuberculosis 1/489 (0.2%) 0/490 (0%)
    Pyelonephritis 1/489 (0.2%) 4/490 (0.8%)
    Renal Abscess 1/489 (0.2%) 0/490 (0%)
    Respiratory Tract Infection 1/489 (0.2%) 1/490 (0.2%)
    Sepsis 7/489 (1.4%) 5/490 (1%)
    Septic Shock 2/489 (0.4%) 1/490 (0.2%)
    Sinusitis 0/489 (0%) 1/490 (0.2%)
    Staphylococcal Infection 0/489 (0%) 1/490 (0.2%)
    Tracheobronchitis 0/489 (0%) 1/490 (0.2%)
    Upper Respiratory Tract Infection 2/489 (0.4%) 0/490 (0%)
    Urinary Tract Infection 7/489 (1.4%) 12/490 (2.4%)
    Urosepsis 2/489 (0.4%) 2/490 (0.4%)
    Injury, poisoning and procedural complications
    Alcohol Poisoning 0/489 (0%) 1/490 (0.2%)
    Ankle Fracture 0/489 (0%) 1/490 (0.2%)
    Cervical Vertebral Fracture 1/489 (0.2%) 0/490 (0%)
    Clavicle Fracture 0/489 (0%) 1/490 (0.2%)
    Fall 1/489 (0.2%) 8/490 (1.6%)
    Femoral Neck Fracture 0/489 (0%) 1/490 (0.2%)
    Femur Fracture 1/489 (0.2%) 3/490 (0.6%)
    Foot Fracture 0/489 (0%) 1/490 (0.2%)
    Hand Fracture 0/489 (0%) 2/490 (0.4%)
    Hip Fracture 0/489 (0%) 1/490 (0.2%)
    Humerus Fracture 0/489 (0%) 1/490 (0.2%)
    Limb Traumatic Amputation 0/489 (0%) 1/490 (0.2%)
    Lower Limb Fracture 1/489 (0.2%) 0/490 (0%)
    Lumbar Vertebral Fracture 2/489 (0.4%) 0/490 (0%)
    Multiple Fractures 0/489 (0%) 1/490 (0.2%)
    Muscle Strain 1/489 (0.2%) 0/490 (0%)
    Pelvic Fracture 0/489 (0%) 1/490 (0.2%)
    Radius Fracture 1/489 (0.2%) 0/490 (0%)
    Rib Fracture 0/489 (0%) 1/490 (0.2%)
    Spinal Compression Fracture 0/489 (0%) 2/490 (0.4%)
    Spinal Fracture 0/489 (0%) 1/490 (0.2%)
    Subdural Haematoma 0/489 (0%) 2/490 (0.4%)
    Toxicity to Various Agents 0/489 (0%) 1/490 (0.2%)
    Traumatic Fracture 0/489 (0%) 1/490 (0.2%)
    Upper Limb Fracture 1/489 (0.2%) 0/490 (0%)
    Investigations
    Alanine Aminotransferase Increased 1/489 (0.2%) 0/490 (0%)
    Blood Creatinine Increased 0/489 (0%) 2/490 (0.4%)
    Oxygen Saturation Decreased 0/489 (0%) 1/490 (0.2%)
    Metabolism and nutrition disorders
    Decreased Appetite 2/489 (0.4%) 0/490 (0%)
    Dehydration 2/489 (0.4%) 2/490 (0.4%)
    Diabetes Mellitus 0/489 (0%) 1/490 (0.2%)
    Diabetes Mellitus Inadequate Control 1/489 (0.2%) 0/490 (0%)
    Failure to Thrive 0/489 (0%) 1/490 (0.2%)
    Hyperglycaemia 3/489 (0.6%) 1/490 (0.2%)
    Hyperkalaemia 1/489 (0.2%) 0/490 (0%)
    Hypokalaemia 2/489 (0.4%) 2/490 (0.4%)
    Hyponatraemia 1/489 (0.2%) 0/490 (0%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 0/489 (0%) 4/490 (0.8%)
    Back Pain 8/489 (1.6%) 4/490 (0.8%)
    Bone Pain 2/489 (0.4%) 3/490 (0.6%)
    Flank Pain 0/489 (0%) 1/490 (0.2%)
    Muscular Weakness 3/489 (0.6%) 0/490 (0%)
    Osteoarthritis 0/489 (0%) 2/490 (0.4%)
    Osteoporosis 0/489 (0%) 1/490 (0.2%)
    Pain in Extremity 0/489 (0%) 3/490 (0.6%)
    Pathological Fracture 3/489 (0.6%) 2/490 (0.4%)
    Rheumatoid Arthritis 0/489 (0%) 1/490 (0.2%)
    Spinal Osteoarthritis 0/489 (0%) 1/490 (0.2%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Astrocytoma 1/489 (0.2%) 0/490 (0%)
    B-Cell Lymphoma 1/489 (0.2%) 0/490 (0%)
    Basal Cell Carcinoma 1/489 (0.2%) 1/490 (0.2%)
    Bladder Transitional Cell Carcinoma 1/489 (0.2%) 0/490 (0%)
    Cancer Pain 1/489 (0.2%) 0/490 (0%)
    Colon Cancer 1/489 (0.2%) 0/490 (0%)
    Colorectal Adenocarcinoma 0/489 (0%) 1/490 (0.2%)
    Gallbladder Cancer 0/489 (0%) 1/490 (0.2%)
    Gastric Neoplasm 1/489 (0.2%) 0/490 (0%)
    Hepatic Cancer 0/489 (0%) 1/490 (0.2%)
    Intestinal Metastasis 0/489 (0%) 1/490 (0.2%)
    Intraductal Papillary Mucinous Neoplasm 0/489 (0%) 1/490 (0.2%)
    Lung Adenocarcinoma 1/489 (0.2%) 0/490 (0%)
    Malignant Melanoma 0/489 (0%) 1/490 (0.2%)
    Metastases to Bone 0/489 (0%) 1/490 (0.2%)
    Metastatic Malignant Melanoma 0/489 (0%) 1/490 (0.2%)
    Oesophageal Adenocarcinoma 0/489 (0%) 1/490 (0.2%)
    Oesophageal Neoplasm 0/489 (0%) 1/490 (0.2%)
    Pancreatic Carcinoma 0/489 (0%) 1/490 (0.2%)
    Prostate Cancer Metastatic 1/489 (0.2%) 0/490 (0%)
    Small Cell Carcinoma 0/489 (0%) 1/490 (0.2%)
    Squamous Cell Carcinoma 0/489 (0%) 1/490 (0.2%)
    Thyroid Cancer 0/489 (0%) 1/490 (0.2%)
    Transitional Cell Carcinoma 0/489 (0%) 1/490 (0.2%)
    Nervous system disorders
    Altered State of Consciousness 0/489 (0%) 1/490 (0.2%)
    Carotid Artery Stenosis 2/489 (0.4%) 0/490 (0%)
    Cerebral Haemorrhage 0/489 (0%) 1/490 (0.2%)
    Cerebrovascular Accident 4/489 (0.8%) 2/490 (0.4%)
    Cognitive Disorder 0/489 (0%) 1/490 (0.2%)
    Dementia 1/489 (0.2%) 1/490 (0.2%)
    Dizziness 1/489 (0.2%) 1/490 (0.2%)
    Embolic Cerebral Infarction 1/489 (0.2%) 0/490 (0%)
    Encephalopathy 1/489 (0.2%) 0/490 (0%)
    Haemorrhagic Stroke 0/489 (0%) 1/490 (0.2%)
    Headache 0/489 (0%) 1/490 (0.2%)
    Ischaemic Stroke 2/489 (0.4%) 1/490 (0.2%)
    Loss of Consciousness 1/489 (0.2%) 0/490 (0%)
    Nervous System Disorder 1/489 (0.2%) 0/490 (0%)
    Neuralgia 0/489 (0%) 1/490 (0.2%)
    Parkinson's Disease 1/489 (0.2%) 0/490 (0%)
    Peripheral Motor Neuropathy 1/489 (0.2%) 0/490 (0%)
    Presyncope 3/489 (0.6%) 1/490 (0.2%)
    Sciatica 0/489 (0%) 1/490 (0.2%)
    Seizure 0/489 (0%) 2/490 (0.4%)
    Spinal Cord Compression 3/489 (0.6%) 5/490 (1%)
    Subarachnoid Haemorrhage 1/489 (0.2%) 0/490 (0%)
    Syncope 5/489 (1%) 6/490 (1.2%)
    Transient Ischaemic Attack 1/489 (0.2%) 3/490 (0.6%)
    Product Issues
    Device Occlusion 0/489 (0%) 2/490 (0.4%)
    Psychiatric disorders
    Anxiety 1/489 (0.2%) 1/490 (0.2%)
    Confusional State 0/489 (0%) 1/490 (0.2%)
    Delirium 0/489 (0%) 1/490 (0.2%)
    Renal and urinary disorders
    Acute Kidney Injury 7/489 (1.4%) 6/490 (1.2%)
    Bladder Obstruction 0/489 (0%) 1/490 (0.2%)
    Calculus Bladder 1/489 (0.2%) 1/490 (0.2%)
    Haematuria 13/489 (2.7%) 6/490 (1.2%)
    Hydronephrosis 0/489 (0%) 4/490 (0.8%)
    Nephrolithiasis 2/489 (0.4%) 1/490 (0.2%)
    Oliguria 1/489 (0.2%) 0/490 (0%)
    Renal Failure 0/489 (0%) 1/490 (0.2%)
    Renal Impairment 0/489 (0%) 1/490 (0.2%)
    Ureteric Obstruction 0/489 (0%) 1/490 (0.2%)
    Urethral Stenosis 1/489 (0.2%) 1/490 (0.2%)
    Urinary Incontinence 1/489 (0.2%) 3/490 (0.6%)
    Urinary Retention 3/489 (0.6%) 3/490 (0.6%)
    Urinary Tract Obstruction 1/489 (0.2%) 4/490 (0.8%)
    Reproductive system and breast disorders
    Testicular Pain 0/489 (0%) 1/490 (0.2%)
    Respiratory, thoracic and mediastinal disorders
    Acute Respiratory Failure 1/489 (0.2%) 1/490 (0.2%)
    Chronic Obstructive Pulmonary Disease 2/489 (0.4%) 1/490 (0.2%)
    Cough 1/489 (0.2%) 0/490 (0%)
    Dyspnoea 1/489 (0.2%) 0/490 (0%)
    Epistaxis 1/489 (0.2%) 1/490 (0.2%)
    Pneumothorax 1/489 (0.2%) 1/490 (0.2%)
    Pulmonary Congestion 1/489 (0.2%) 0/490 (0%)
    Pulmonary Embolism 6/489 (1.2%) 1/490 (0.2%)
    Pulmonary Fibrosis 1/489 (0.2%) 0/490 (0%)
    Pulmonary Oedema 1/489 (0.2%) 0/490 (0%)
    Respiratory Failure 3/489 (0.6%) 0/490 (0%)
    Skin and subcutaneous tissue disorders
    Rash 0/489 (0%) 2/490 (0.4%)
    Rash Pruritic 0/489 (0%) 1/490 (0.2%)
    Skin Ulcer 1/489 (0.2%) 0/490 (0%)
    Subcutaneous Emphysema 1/489 (0.2%) 0/490 (0%)
    Surgical and medical procedures
    Coronary Angioplasty 1/489 (0.2%) 0/490 (0%)
    Vascular disorders
    Aortic Aneurysm 2/489 (0.4%) 2/490 (0.4%)
    Aortic Dissection 0/489 (0%) 1/490 (0.2%)
    Aortic Stenosis 1/489 (0.2%) 0/490 (0%)
    Deep Vein Thrombosis 4/489 (0.8%) 1/490 (0.2%)
    Embolism 2/489 (0.4%) 0/490 (0%)
    Haemodynamic Instability 1/489 (0.2%) 0/490 (0%)
    Hypertension 3/489 (0.6%) 1/490 (0.2%)
    Hypertensive Urgency 0/489 (0%) 1/490 (0.2%)
    Hypotension 1/489 (0.2%) 1/490 (0.2%)
    Pelvic Venous Thrombosis 1/489 (0.2%) 0/490 (0%)
    Peripheral Arterial Occlusive Disease 1/489 (0.2%) 0/490 (0%)
    Peripheral Ischaemia 0/489 (0%) 1/490 (0.2%)
    Thrombosis 0/489 (0%) 1/490 (0.2%)
    Other (Not Including Serious) Adverse Events
    Placebo+ Abiraterone Acetate - Prednisolone Apalutamide + Abiraterone Acetate - Prednisolone
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 459/489 (93.9%) 472/490 (96.3%)
    Blood and lymphatic system disorders
    Anaemia 77/489 (15.7%) 70/490 (14.3%)
    Endocrine disorders
    Hypothyroidism 8/489 (1.6%) 27/490 (5.5%)
    Gastrointestinal disorders
    Abdominal Pain 25/489 (5.1%) 24/490 (4.9%)
    Constipation 94/489 (19.2%) 96/490 (19.6%)
    Diarrhoea 73/489 (14.9%) 91/490 (18.6%)
    Dyspepsia 21/489 (4.3%) 28/490 (5.7%)
    Nausea 76/489 (15.5%) 84/490 (17.1%)
    Vomiting 35/489 (7.2%) 39/490 (8%)
    General disorders
    Asthenia 63/489 (12.9%) 65/490 (13.3%)
    Fatigue 134/489 (27.4%) 164/490 (33.5%)
    Oedema Peripheral 72/489 (14.7%) 77/490 (15.7%)
    Pyrexia 36/489 (7.4%) 36/490 (7.3%)
    Infections and infestations
    Influenza 28/489 (5.7%) 20/490 (4.1%)
    Nasopharyngitis 57/489 (11.7%) 52/490 (10.6%)
    Upper Respiratory Tract Infection 40/489 (8.2%) 42/490 (8.6%)
    Urinary Tract Infection 49/489 (10%) 37/490 (7.6%)
    Injury, poisoning and procedural complications
    Contusion 49/489 (10%) 34/490 (6.9%)
    Fall 92/489 (18.8%) 106/490 (21.6%)
    Rib Fracture 23/489 (4.7%) 25/490 (5.1%)
    Investigations
    Alanine Aminotransferase Increased 57/489 (11.7%) 20/490 (4.1%)
    Aspartate Aminotransferase Increased 53/489 (10.8%) 21/490 (4.3%)
    Blood Alkaline Phosphatase Increased 34/489 (7%) 19/490 (3.9%)
    Blood Pressure Increased 17/489 (3.5%) 26/490 (5.3%)
    Weight Decreased 84/489 (17.2%) 136/490 (27.8%)
    Weight Increased 28/489 (5.7%) 12/490 (2.4%)
    Metabolism and nutrition disorders
    Decreased Appetite 60/489 (12.3%) 72/490 (14.7%)
    Hypercholesterolaemia 18/489 (3.7%) 28/490 (5.7%)
    Hyperglycaemia 37/489 (7.6%) 29/490 (5.9%)
    Hypokalaemia 73/489 (14.9%) 79/490 (16.1%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 121/489 (24.7%) 127/490 (25.9%)
    Back Pain 133/489 (27.2%) 154/490 (31.4%)
    Bone Pain 48/489 (9.8%) 34/490 (6.9%)
    Muscle Spasms 45/489 (9.2%) 30/490 (6.1%)
    Musculoskeletal Chest Pain 50/489 (10.2%) 48/490 (9.8%)
    Musculoskeletal Pain 46/489 (9.4%) 50/490 (10.2%)
    Myalgia 28/489 (5.7%) 27/490 (5.5%)
    Neck Pain 13/489 (2.7%) 26/490 (5.3%)
    Pain in Extremity 57/489 (11.7%) 79/490 (16.1%)
    Nervous system disorders
    Dizziness 46/489 (9.4%) 61/490 (12.4%)
    Dysgeusia 12/489 (2.5%) 33/490 (6.7%)
    Headache 63/489 (12.9%) 79/490 (16.1%)
    Psychiatric disorders
    Anxiety 16/489 (3.3%) 28/490 (5.7%)
    Insomnia 30/489 (6.1%) 46/490 (9.4%)
    Renal and urinary disorders
    Haematuria 40/489 (8.2%) 42/490 (8.6%)
    Pollakiuria 31/489 (6.3%) 21/490 (4.3%)
    Respiratory, thoracic and mediastinal disorders
    Cough 66/489 (13.5%) 53/490 (10.8%)
    Dyspnoea 43/489 (8.8%) 41/490 (8.4%)
    Skin and subcutaneous tissue disorders
    Rash 24/489 (4.9%) 44/490 (9%)
    Vascular disorders
    Hot Flush 56/489 (11.5%) 74/490 (15.1%)
    Hypertension 122/489 (24.9%) 144/490 (29.4%)

    Limitations/Caveats

    This study used an electronic handheld device to collect responses for patient-reported outcome (PRO) questionnaires, which might have resulted in a lower-than-expected compliance due to unfamiliarity of the elderly population with the device.

    More Information

    Certain Agreements

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

    If an investigator wishes to publish information from the study, a copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation.

    Results Point of Contact

    Name/Title Executive Medical Director
    Organization Aragon Pharmaceuticals, Inc.
    Phone 844-434-4210
    Email ClinicalTrialDisclosure@its.jnj.com
    Responsible Party:
    Aragon Pharmaceuticals, Inc.
    ClinicalTrials.gov Identifier:
    NCT02257736
    Other Study ID Numbers:
    • CR105505
    • 56021927PCR3001
    • 2014-001718-25
    First Posted:
    Oct 6, 2014
    Last Update Posted:
    Aug 4, 2022
    Last Verified:
    Aug 1, 2022