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TITAN: A Study of Apalutamide (JNJ-56021927, ARN-509) Plus Androgen Deprivation Therapy (ADT) Versus ADT in Participants With mHSPC

Sponsor
Aragon Pharmaceuticals, Inc. (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT02489318
Collaborator
(none)
1,052
Enrollment
229
Locations
2
Arms
102.1
Anticipated Duration (Months)
4.6
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to determine if the addition of apalutamide to ADT provides superior efficacy in improving radiographic progression-free survival (rPFS) or overall survival (OS) for participants with mHSPC.

Condition or Disease Intervention/Treatment Phase
Phase 3

Detailed Description

This is a randomized (study medication assigned to participants by chance), double-blind (neither the researchers nor the participants know what treatment the participant is receiving), placebo-controlled, multinational, multicenter study of apalutamide in participants with mHSPC. The study consists of 4 Phases: Screening Phase (up to 28 days before randomization), Treatment Phase (28 day treatment cycles until disease progression or the occurrence of unacceptable treatment related toxicity), an End of Treatment Phase (until 30 days after the last dose of study drug), and then a Survival Follow up Phase. In the event of a positive study result and notification of unblinding at either of the interim analyses or at the final analysis, participants in the treatment Phase will have the opportunity to enroll in an Open-label Extension Phase, which will allow participants to receive active drug (apalutamide) for approximately 3 years. Participants who are receiving apalutamide in the Open-label Extension Phase may continue receiving apalutamide in the Long-term Extension (LTE) Phase if they will continue to derive benefit from treatment (based on investigator assessment). Participants' safety will be monitored throughout the study.

Study Design

Study Type:
Interventional
Actual Enrollment :
1052 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Care Provider, Investigator)
Primary Purpose:
Treatment
Official Title:
A Phase 3 Randomized, Placebo-controlled, Double-blind Study of Apalutamide Plus Androgen Deprivation Therapy (ADT) Versus ADT in Subjects With Metastatic Hormone-sensitive Prostate Cancer (mHSPC)
Actual Study Start Date :
Nov 27, 2015
Actual Primary Completion Date :
Sep 7, 2020
Anticipated Study Completion Date :
May 31, 2024

Arms and Interventions

Arm Intervention/Treatment
Experimental: Apalutamide plus ADT

Participants will receive apalutamide 240 milligram (mg) (4X 60 mg tablets) with ADT.

Drug: Apalutamide
Participants will receive apalutamide 240 mg (4 x 60 mg) tablets orally once daily in each 28 day treatment cycles.
Other Names:
  • JNJ-56021927
  • ARN-509

    • Drug: Androgen Deprivation Therapy (ADT)
    All participants will receive and remain on a stable regimen of ADT (gonadotropin releasing hormone analog [GnRHa] or surgical castration). The choice of the GnRHa (agonist or antagonist) will be at discretion of the Investigator. Dosing (dose and frequency of administration) will be consistent with the prescribing information.
    Experimental: Placebo plus ADT

    Participants will receive matching Placebo with ADT.

    Drug: Placebo
    Participants will receive Placebo orally once daily in each 28 day treatment cycles.

    Drug: Androgen Deprivation Therapy (ADT)
    All participants will receive and remain on a stable regimen of ADT (gonadotropin releasing hormone analog [GnRHa] or surgical castration). The choice of the GnRHa (agonist or antagonist) will be at discretion of the Investigator. Dosing (dose and frequency of administration) will be consistent with the prescribing information.

    Outcome Measures

    Primary Outcome Measures

    1. Radiographic Progression-free Survival (rPFS) [Up to 35 months]

      rPFS as assessed by the investigator was defined as the duration from the date of randomization to the date of first documentation of radiographic progressive disease or death due to any cause, whichever occurred first. Radiographic progressive disease was defined as progression of soft tissue lesions measured by computed tomography (CT) or magnetic resonance imaging (MRI) as defined by modified Response evaluation criteria in solid tumors (RECIST) 1.1.

    2. Overall Survival (OS) [Up to 57 months]

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

    Secondary Outcome Measures

    1. Time to Initiation of Cytotoxic Chemotherapy [Up to 57 months]

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

    2. Time to Pain Progression [Up to 57 months]

      Time to pain progression was defined as the time from the date of randomization to the date of the first observation of pain progression. Pain progression was defined as an average increase by 2 points from baseline to greater than (>) 4 on the Brief Pain Inventory - Short Form (BPI-SF) worst pain intensity (item 3) with no decrease in opioids confirmed greater than equal to (>=) 3 weeks apart or initiation of chronic opioids, 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.

    3. Time to Chronic Opioid Use [Up to 57 months]

      Time to chronic opioid use was defined as the time from date of randomization to the first date of confirmed chronic opioid use. For participants entering the study without receiving opioids, chronic opioid use was defined as administration of opioid analgesics lasting for greater than or equal to (>=) 3 weeks for oral or >=7 days for non-oral formulations. For participants entering the study already receiving opioids, chronic opioid use was defined as a >=30 percent (%) increase in total daily dose of the opioid analgesics lasting for >= 3 weeks for oral or >= 7 days for non-oral formulation.

    4. Time to Skeletal-related Event (SRE) [Up to 57 months]

      Time to SRE was defined as the time from the date of randomization to the date of the first observation of an SRE. A SRE was defined as the occurrence of either a pathological fracture, or spinal cord compression, or radiation to bone, or surgery to bone.

    Eligibility Criteria

    Criteria

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

    • Diagnosis of prostate adenocarcinoma as confirmed by the investigator

    • Metastatic disease documented by greater than or equal to (>=) 1 bone lesions on 99mTc bone scan. Participants with a single bone lesion must have confirmation of bone metastasis by computed tomography (CT) or magnetic resonance imaging (MRI)

    • Eastern Cooperative Oncology Group Performance Status (ECOG PS) grade of 0 or 1

    • Participants who received docetaxel treatment must meet the following criteria: a) Received a maximum of 6 cycles of docetaxel therapy for mHSPC; b) Received the last dose of docetaxel <=2 months prior to randomization; c) Maintained a response to docetaxel of stable disease or better, by investigator assessment of imaging and PSA, prior to randomization

    • Other allowed prior treatment for mHSPC: a) Maximum of 1 course of radiation or surgical intervention; radiation therapy for metastatic lesions must be completed prior to randomization; b) Less than or equal to (<=) 6 months of ADT prior to randomization

    • Allowed prior treatments for localized prostate cancer (all treatments must have been completed >= 1 year prior to randomization) a) <= 3 years total of ADT; b) All other forms of prior therapies including radiation therapy, prostatectomy,lymph node dissection, and systemic therapies

    Exclusion Criteria:

    • Pathological finding consistent with small cell, ductal or neuroendocrine carcinoma of the prostate

    • Known brain metastases

    • Lymph nodes as only sites of metastases

    • Visceral (ie, liver or lung) metastases as only sites of metastases

    • Other prior malignancy less than or equal to 5 years prior to randomization with the exception of squamous or basal cell skin carcinoma or non-invasive superficial bladder cancer

    • Prior treatment with other next generation anti-androgens or other CYP17 inhibitors, immunotherapy or radiopharmaceutical agents for prostate cancer

    • History of seizures or medications known to lower seizure threshold

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Homewood Alabama United States
    2 Tucson Arizona United States
    3 San Bernardino California United States
    4 San Diego California United States
    5 Denver Colorado United States
    6 Norwalk Connecticut United States
    7 Fort Myers Florida United States
    8 Chicago Illinois United States
    9 Fort Wayne Indiana United States
    10 Jeffersonville Indiana United States
    11 New Orleans Louisiana United States
    12 Baltimore Maryland United States
    13 Rockville Maryland United States
    14 Lansing Michigan United States
    15 Troy Michigan United States
    16 Omaha Nebraska United States
    17 Las Vegas Nevada United States
    18 Bronx New York United States
    19 Brooklyn New York United States
    20 Poughkeepsie New York United States
    21 Syracuse New York United States
    22 Raleigh North Carolina United States
    23 Salisbury North Carolina United States
    24 Cleveland Ohio United States
    25 Middleburg Heights Ohio United States
    26 Springfield Oregon United States
    27 Bala-Cynwyd Pennsylvania United States
    28 Bryn Mawr Pennsylvania United States
    29 Lancaster Pennsylvania United States
    30 Charleston South Carolina United States
    31 Nashville Tennessee United States
    32 Dallas Texas United States
    33 Houston Texas United States
    34 San Antonio Texas United States
    35 Salt Lake City Utah United States
    36 Richmond Virginia United States
    37 Virginia Beach Virginia United States
    38 Burien Washington United States
    39 Spokane Washington United States
    40 Milwaukee Wisconsin United States
    41 Berazategui Argentina
    42 C.a.b.a. Argentina
    43 Capital Federal Argentina
    44 Ciudad Automoma Buenos Aires Argentina
    45 Ciudad Autonoma de Buenos Aires Argentina
    46 Ciudad De Buenos Aires Argentina
    47 Cordoba Argentina
    48 La Plata Argentina
    49 Pergamino Argentina
    50 Rosario Argentina
    51 San Miguel de Tucuman Argentina
    52 San Salvador de Jujuy Argentina
    53 Albury Australia
    54 Elizabeth Vale Australia
    55 Kogarah Australia
    56 Port Macquarie Australia
    57 South Brisbane Australia
    58 St Leonards Australia
    59 Barretos Brazil
    60 Florianópolis Brazil
    61 Goiânia Brazil
    62 Ijui Brazil
    63 Natal Brazil
    64 Ribeirao Preto Brazil
    65 Rio de Janeiro Brazil
    66 Salvador Brazil
    67 Santo André Brazil
    68 Sao Paulo Brazil
    69 Sorocaba Brazil
    70 São Paulo Brazil
    71 Calgary Alberta Canada
    72 Vancouver British Columbia Canada
    73 Hamilton Ontario Canada
    74 Kingston Ontario Canada
    75 Toronto Ontario Canada
    76 Quebec Canada
    77 Beijing China
    78 ChengDu China
    79 ChongQing China
    80 Fuzhou China
    81 Guangzhou China
    82 Hangzhou China
    83 NanJing China
    84 ShangHai China
    85 Suzhou China
    86 WuHan China
    87 Wuxi China
    88 Xi'An China
    89 Hradec Králove Czechia
    90 Liberec Czechia
    91 Nový Jicin Czechia
    92 Olomouc Czechia
    93 Opava Czechia
    94 Pardubice Czechia
    95 Praha 10 Czechia
    96 Praha 2 Czechia
    97 Praha 4 Czechia
    98 Praha 5 Czechia
    99 Praha 8 Czechia
    100 Zlin Czechia
    101 Clermont Ferrand France
    102 Montpellier France
    103 Nancy France
    104 Paris France
    105 Pierre Bénite France
    106 Strasbourg France
    107 Suresnes France
    108 Bonn Germany
    109 Braunschweig Germany
    110 Hamburg Germany
    111 Hannover Germany
    112 Leipzig Germany
    113 Lubeck Germany
    114 Lutherstadt Eisleben Germany
    115 Nürtingen Germany
    116 Sindelfingen Germany
    117 Straubing Germany
    118 Budapest Hungary
    119 Győr Hungary
    120 Pécs Hungary
    121 Sopron Hungary
    122 Beer Sheva Israel
    123 Haifa Israel
    124 Holon Israel
    125 Kfar Saba Israel
    126 Petach Tikva Israel
    127 Ramat Gan Israel
    128 Zrifin Israel
    129 Chuo-ku, Chiba-City, Japan
    130 Hakata-Ku Japan
    131 Koshigaya Japan
    132 Matsuyama Japan
    133 Minami-Ku, Sagamihara-Shi Japan
    134 Miyazaki Japan
    135 Nagano-shi Japan
    136 Nagasaki-shi Japan
    137 Osaka-Sayama-shi Japan
    138 Osaka Japan
    139 Sakura Japan
    140 Sapporo Japan
    141 Yokohama Japan
    142 Yufu Japan
    143 Daegu Korea, Republic of
    144 Daejeon Korea, Republic of
    145 Goyang-Si Korea, Republic of
    146 Jeollanam-do Korea, Republic of
    147 Seongnam-si Korea, Republic of
    148 Seoul Korea, Republic of
    149 Ciudad de México Mexico
    150 Durango Mexico
    151 Guadalajara Mexico
    152 Leon Mexico
    153 Mexico City Mexico
    154 Mexico Mexico
    155 Morelia Mexico
    156 Zapopan Mexico
    157 Bialystok Poland
    158 Bydgoszcz Poland
    159 Krakow Poland
    160 Kutno Poland
    161 Lodz Poland
    162 Lublin Poland
    163 Siedlce Poland
    164 Sochaczew Poland
    165 Warszawa Poland
    166 Wroclaw Poland
    167 Bucharest Romania
    168 Cluj Napoca Romania
    169 Craiova Romania
    170 Targu Mures Romania
    171 Barnaul Russian Federation
    172 Ivanovo Russian Federation
    173 Moscow Russian Federation
    174 Nizhny Novgorod Russian Federation
    175 Obninsk Russian Federation
    176 Omsk Russian Federation
    177 Pyatigorsk Russian Federation
    178 Rostov-on-Don Russian Federation
    179 Ryazan Russian Federation
    180 Saint-Petersburg Russian Federation
    181 Saransk Russian Federation
    182 Sochi Russian Federation
    183 St Petersburg Russian Federation
    184 Tambov Russian Federation
    185 Tomsk Russian Federation
    186 Tyumen Russian Federation
    187 Ufa Russian Federation
    188 Vologda Russian Federation
    189 Barcelona Spain
    190 Cordoba Spain
    191 Jerez de la Frontera Spain
    192 Madrid Spain
    193 Pamplona Spain
    194 Göteborg Sweden
    195 Malmö Sweden
    196 Stockholm Sweden
    197 Umeå Sweden
    198 Uppsala Sweden
    199 Växjö Sweden
    200 Örebro Sweden
    201 Ankara Turkey
    202 Edirne Turkey
    203 Istanbul Turkey
    204 Izmir Turkey
    205 Mersin Turkey
    206 Cherkasy Ukraine
    207 Dnipo Ukraine
    208 Dnipro Ukraine
    209 Ivano-Frankivsk Ukraine
    210 Khakhiv Ukraine
    211 Kharkiv Ukraine
    212 Khmelnytsky Ukraine
    213 Kyiv Ukraine
    214 Lviv Ukraine
    215 Odesa Ukraine
    216 Poltava Ukraine
    217 Uzhgorod Ukraine
    218 Vinnitsa Ukraine
    219 Zaporizhzhya Ukraine
    220 Carlisle United Kingdom
    221 Dundee United Kingdom
    222 Glasgow United Kingdom
    223 London United Kingdom
    224 Newcastle Upon Tyne United Kingdom
    225 Oxford United Kingdom
    226 Plymouth United Kingdom
    227 Scunthorpe United Kingdom
    228 Stockton on Tees United Kingdom
    229 Wolverhampton 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:
    NCT02489318
    Other Study ID Numbers:
    • CR107614
    • 2015-000735-32
    • 56021927PCR3002
    First Posted:
    Jul 3, 2015
    Last Update Posted:
    Aug 4, 2022
    Last Verified:
    Aug 1, 2022
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Aragon Pharmaceuticals, Inc.
    Prostate Cancer
    JNJ-56021927
    Androgen Deprivation Therapy
    ARN-509
    Apalutamide
    TITAN
    Metastatic Hormone-sensitive Prostate Cancer
    Additional relevant MeSH terms:
    Prostatic Neoplasms
    Androgens

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail Per protocol, 208 participants randomized to receive placebo+ADT were switched over to receive apalutamide+ADT after interim analysis and unblinding. Randomized treatment disposition has been reported in participant flow. Response/progression that occurred during a non-randomized switch-over to apalutamide+ADT were not counted towards efficacy outcome measures.
    Arm/Group Title Placebo + Androgen Deprivation Therapy (ADT) Apalutamide + ADT
    Arm/Group Description Participants received matching placebo (4 tablets) orally once daily (qd) along with ADT (gonadotropin releasing hormone analog [GnRHa] or surgical castration) as standard of care therapy in each 28-day treatment cycle. The choice of the GnRHa (agonist or antagonist) was at discretion of the investigator. In the event of a positive result at interim or final analysis participants in treatment phase had opportunity to receive Apalutamide +ADT. Participants received treatment until radiographic progression or unequivocal clinical progression, unacceptable toxicity, or death. Participants received JNJ-56021927 (apalutamide) 240 milligrams (mg) (4*60 mg tablets) orally qd along with ADT (gonadotropin releasing hormone analog [GnRHa] or surgical castration) as standard of care therapy in each 28-day treatment cycle. The choice of the GnRHa (agonist or antagonist) was at discretion of the investigator. Participants received treatment until radiographic progression or unequivocal clinical progression, unacceptable toxicity, or death.
    Period Title: Randomized
    STARTED 527 525
    COMPLETED 527 524
    NOT COMPLETED 0 1
    Period Title: Randomized
    STARTED 527 524
    COMPLETED 208 0
    NOT COMPLETED 319 524

    Baseline Characteristics

    Arm/Group Title Placebo + Androgen Deprivation Therapy (ADT) Apalutamide + ADT Total
    Arm/Group Description Participants received matching placebo (4 tablets) orally once daily (qd) along with ADT (gonadotropin releasing hormone analog [GnRHa] or surgical castration) as standard of care therapy in each 28-day treatment cycle. The choice of the GnRHa (agonist or antagonist) was at discretion of the investigator. In the event of a positive result at interim or final analysis participants in treatment phase had opportunity to receive Apalutamide +ADT. Participants received treatment until radiographic progression or unequivocal clinical progression, unacceptable toxicity, or death. Participants received JNJ-56021927 (apalutamide) 240 milligrams (mg) (4*60 mg tablets) orally qd along with ADT (gonadotropin releasing hormone analog [GnRHa] or surgical castration) as standard of care therapy in each 28-day treatment cycle. The choice of the GnRHa (agonist or antagonist) was at discretion of the investigator. Participants received treatment until radiographic progression or unequivocal clinical progression, unacceptable toxicity, or death. Total of all reporting groups
    Overall Participants 527 525 1052
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    67.9
    (8.42)
    68.9
    (8.11)
    68.4
    (8.28)
    Sex: Female, Male (Count of Participants)
    Female
    0
    0%
    0
    0%
    0
    0%
    Male
    527
    100%
    525
    100%
    1052
    100%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    11
    2.1%
    6
    1.1%
    17
    1.6%
    Asian
    112
    21.3%
    119
    22.7%
    231
    22%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    9
    1.7%
    10
    1.9%
    19
    1.8%
    White
    365
    69.3%
    354
    67.4%
    719
    68.3%
    More than one race
    0
    0%
    1
    0.2%
    1
    0.1%
    Unknown or Not Reported
    30
    5.7%
    35
    6.7%
    65
    6.2%
    Region of Enrollment (participants) [Number]
    ARGENTINA
    20
    3.8%
    17
    3.2%
    37
    3.5%
    AUSTRALIA
    5
    0.9%
    6
    1.1%
    11
    1%
    BRAZIL
    38
    7.2%
    54
    10.3%
    92
    8.7%
    CANADA
    16
    3%
    14
    2.7%
    30
    2.9%
    CHINA
    46
    8.7%
    48
    9.1%
    94
    8.9%
    CZECH REPUBLIC
    12
    2.3%
    19
    3.6%
    31
    2.9%
    FRANCE
    8
    1.5%
    8
    1.5%
    16
    1.5%
    GERMANY
    10
    1.9%
    7
    1.3%
    17
    1.6%
    HUNGARY
    11
    2.1%
    13
    2.5%
    24
    2.3%
    ISRAEL
    8
    1.5%
    6
    1.1%
    14
    1.3%
    ITALY
    18
    3.4%
    16
    3%
    34
    3.2%
    JAPAN
    23
    4.4%
    28
    5.3%
    51
    4.8%
    MEXICO
    25
    4.7%
    23
    4.4%
    48
    4.6%
    POLAND
    12
    2.3%
    7
    1.3%
    19
    1.8%
    ROMANIA
    7
    1.3%
    4
    0.8%
    11
    1%
    RUSSIAN FEDERATION
    66
    12.5%
    65
    12.4%
    131
    12.5%
    SOUTH KOREA
    41
    7.8%
    35
    6.7%
    76
    7.2%
    SPAIN
    12
    2.3%
    8
    1.5%
    20
    1.9%
    SWEDEN
    8
    1.5%
    8
    1.5%
    16
    1.5%
    TURKEY
    22
    4.2%
    28
    5.3%
    50
    4.8%
    UKRAINE
    60
    11.4%
    42
    8%
    102
    9.7%
    UNITED KINGDOM
    16
    3%
    20
    3.8%
    36
    3.4%
    UNITED STATES
    43
    8.2%
    49
    9.3%
    92
    8.7%
    Race (NIH/OMB) (participants) [Number]
    American Indian or Alaska Native
    11
    2.1%
    6
    1.1%
    17
    1.6%
    Asian
    112
    21.3%
    119
    22.7%
    231
    22%
    Black or African American
    9
    1.7%
    10
    1.9%
    19
    1.8%
    More than one race
    0
    0%
    1
    0.2%
    1
    0.1%
    Not Reported
    8
    1.5%
    11
    2.1%
    19
    1.8%
    Other
    22
    4.2%
    24
    4.6%
    46
    4.4%
    White
    365
    69.3%
    354
    67.4%
    719
    68.3%

    Outcome Measures

    1. Primary Outcome
    Title Radiographic Progression-free Survival (rPFS)
    Description rPFS as assessed by the investigator was defined as the duration from the date of randomization to the date of first documentation of radiographic progressive disease or death due to any cause, whichever occurred first. Radiographic progressive disease was defined as progression of soft tissue lesions measured by computed tomography (CT) or magnetic resonance imaging (MRI) as defined by modified Response evaluation criteria in solid tumors (RECIST) 1.1.
    Time Frame Up to 35 months

    Outcome Measure Data

    Analysis Population Description
    Intent to treat (ITT) population included all randomized participants classified according to their assigned treatment group, regardless of the actual treatment received.
    Arm/Group Title Placebo + Androgen Deprivation Therapy (ADT) Apalutamide + ADT
    Arm/Group Description Participants received matching placebo (4 tablets) orally once daily (qd) along with ADT (gonadotropin releasing hormone analog [GnRHa] or surgical castration) as standard of care therapy in each 28-day treatment cycle. The choice of the GnRHa (agonist or antagonist) was at discretion of the investigator. In the event of a positive result at interim or final analysis participants in treatment phase had opportunity to receive Apalutamide +ADT. Participants received treatment until radiographic progression or unequivocal clinical progression, unacceptable toxicity, or death. Participants received JNJ-56021927 (apalutamide) 240 milligrams (mg) (4*60 mg tablets) orally qd along with ADT (gonadotropin releasing hormone analog [GnRHa] or surgical castration) as standard of care therapy in each 28-day treatment cycle. The choice of the GnRHa (agonist or antagonist) was at discretion of the investigator. Participants received treatment until radiographic progression or unequivocal clinical progression, unacceptable toxicity, or death.
    Measure Participants 527 525
    Median (95% Confidence Interval) [months]
    22.08
    NA
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo + Androgen Deprivation Therapy (ADT), Apalutamide + ADT
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method Log Rank
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.484
    Confidence Interval (2-Sided) 95%
    0.391 to 0.600
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Primary Outcome
    Title Overall Survival (OS)
    Description OS was defined as the time from date of randomization to date of death from any cause.
    Time Frame Up to 57 months

    Outcome Measure Data

    Analysis Population Description
    ITT population included all randomized participants classified according to their assigned treatment group, regardless of the actual treatment received.
    Arm/Group Title Placebo + Androgen Deprivation Therapy (ADT) Apalutamide + ADT
    Arm/Group Description Participants received matching placebo (4 tablets) orally once daily (qd) along with ADT (gonadotropin releasing hormone analog [GnRHa] or surgical castration) as standard of care therapy in each 28-day treatment cycle. The choice of the GnRHa (agonist or antagonist) was at discretion of the investigator. In the event of a positive result at interim or final analysis participants in treatment phase had opportunity to receive Apalutamide +ADT. Participants received treatment until radiographic progression or unequivocal clinical progression, unacceptable toxicity, or death. Participants received JNJ-56021927 (apalutamide) 240 milligrams (mg) (4*60 mg tablets) orally qd along with ADT (gonadotropin releasing hormone analog [GnRHa] or surgical castration) as standard of care therapy in each 28-day treatment cycle. The choice of the GnRHa (agonist or antagonist) was at discretion of the investigator. Participants received treatment until radiographic progression or unequivocal clinical progression, unacceptable toxicity, or death.
    Measure Participants 527 525
    Median (95% Confidence Interval) [months]
    52.17
    NA
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo + Androgen Deprivation Therapy (ADT), Apalutamide + ADT
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method Log Rank
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.651
    Confidence Interval (2-Sided) 95%
    0.534 to 0.793
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    3. 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 for prostate cancer.
    Time Frame Up to 57 months

    Outcome Measure Data

    Analysis Population Description
    ITT population included all randomized participants classified according to their assigned treatment group, regardless of the actual treatment received.
    Arm/Group Title Placebo + Androgen Deprivation Therapy (ADT) Apalutamide + ADT
    Arm/Group Description Participants received matching placebo (4 tablets) orally once daily (qd) along with ADT (gonadotropin releasing hormone analog [GnRHa] or surgical castration) as standard of care therapy in each 28-day treatment cycle. The choice of the GnRHa (agonist or antagonist) was at discretion of the investigator. In the event of a positive result at interim or final analysis participants in treatment phase had opportunity to receive Apalutamide +ADT. Participants received treatment until radiographic progression or unequivocal clinical progression, unacceptable toxicity, or death. Participants received JNJ-56021927 (apalutamide) 240 milligrams (mg) (4*60 mg tablets) orally qd along with ADT (gonadotropin releasing hormone analog [GnRHa] or surgical castration) as standard of care therapy in each 28-day treatment cycle. The choice of the GnRHa (agonist or antagonist) was at discretion of the investigator. Participants received treatment until radiographic progression or unequivocal clinical progression, unacceptable toxicity, or death.
    Measure Participants 527 525
    Median (95% Confidence Interval) [months]
    NA
    NA
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo + Androgen Deprivation Therapy (ADT), Apalutamide + ADT
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <.0001
    Comments
    Method Log Rank
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.469
    Confidence Interval (2-Sided) 95%
    0.350 to 0.630
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    4. Secondary Outcome
    Title Time to Pain Progression
    Description Time to pain progression was defined as the time from the date of randomization to the date of the first observation of pain progression. Pain progression was defined as an average increase by 2 points from baseline to greater than (>) 4 on the Brief Pain Inventory - Short Form (BPI-SF) worst pain intensity (item 3) with no decrease in opioids confirmed greater than equal to (>=) 3 weeks apart or initiation of chronic opioids, 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.
    Time Frame Up to 57 months

    Outcome Measure Data

    Analysis Population Description
    ITT population included all randomized participants classified according to their assigned treatment group, regardless of the actual treatment received.
    Arm/Group Title Placebo + Androgen Deprivation Therapy (ADT) Apalutamide + ADT
    Arm/Group Description Participants received matching placebo (4 tablets) orally once daily (qd) along with ADT (gonadotropin releasing hormone analog [GnRHa] or surgical castration) as standard of care therapy in each 28-day treatment cycle. The choice of the GnRHa (agonist or antagonist) was at discretion of the investigator. In the event of a positive result at interim or final analysis participants in treatment phase had opportunity to receive Apalutamide +ADT. Participants received treatment until radiographic progression or unequivocal clinical progression, unacceptable toxicity, or death. Participants received JNJ-56021927 (apalutamide) 240 milligrams (mg) (4*60 mg tablets) orally qd along with ADT (gonadotropin releasing hormone analog [GnRHa] or surgical castration) as standard of care therapy in each 28-day treatment cycle. The choice of the GnRHa (agonist or antagonist) was at discretion of the investigator. Participants received treatment until radiographic progression or unequivocal clinical progression, unacceptable toxicity, or death.
    Measure Participants 527 525
    Median (95% Confidence Interval) [months]
    NA
    NA
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo + Androgen Deprivation Therapy (ADT), Apalutamide + ADT
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.1966
    Comments
    Method Log Rank
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.868
    Confidence Interval (2-Sided) 95%
    0.700 to 1.076
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    5. 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 confirmed chronic opioid use. For participants entering the study without receiving opioids, chronic opioid use was defined as administration of opioid analgesics lasting for greater than or equal to (>=) 3 weeks for oral or >=7 days for non-oral formulations. For participants entering the study already receiving opioids, chronic opioid use was defined as a >=30 percent (%) increase in total daily dose of the opioid analgesics lasting for >= 3 weeks for oral or >= 7 days for non-oral formulation.
    Time Frame Up to 57 months

    Outcome Measure Data

    Analysis Population Description
    ITT population included all randomized participants classified according to their assigned treatment group, regardless of the actual treatment received.
    Arm/Group Title Placebo + Androgen Deprivation Therapy (ADT) Apalutamide + ADT
    Arm/Group Description Participants received matching placebo (4 tablets) orally once daily (qd) along with ADT (gonadotropin releasing hormone analog [GnRHa] or surgical castration) as standard of care therapy in each 28-day treatment cycle. The choice of the GnRHa (agonist or antagonist) was at discretion of the investigator. In the event of a positive result at interim or final analysis participants in treatment phase had opportunity to receive Apalutamide +ADT. Participants received treatment until radiographic progression or unequivocal clinical progression, unacceptable toxicity, or death. Participants received JNJ-56021927 (apalutamide) 240 milligrams (mg) (4*60 mg tablets) orally qd along with ADT (gonadotropin releasing hormone analog [GnRHa] or surgical castration) as standard of care therapy in each 28-day treatment cycle. The choice of the GnRHa (agonist or antagonist) was at discretion of the investigator. Participants received treatment until radiographic progression or unequivocal clinical progression, unacceptable toxicity, or death.
    Measure Participants 527 525
    Median (95% Confidence Interval) [months]
    NA
    NA
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo + Androgen Deprivation Therapy (ADT), Apalutamide + ADT
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.1563
    Comments
    Method Log Rank
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.794
    Confidence Interval (2-Sided) 95%
    0.576 to 1.094
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    6. Secondary Outcome
    Title Time to Skeletal-related Event (SRE)
    Description Time to SRE was defined as the time from the date of randomization to the date of the first observation of an SRE. A SRE was defined as the occurrence of either a pathological fracture, or spinal cord compression, or radiation to bone, or surgery to bone.
    Time Frame Up to 57 months

    Outcome Measure Data

    Analysis Population Description
    ITT population included all randomized participants classified according to their assigned treatment group, regardless of the actual treatment received.
    Arm/Group Title Placebo + Androgen Deprivation Therapy (ADT) Apalutamide + ADT
    Arm/Group Description Participants received matching placebo (4 tablets) orally once daily (qd) along with ADT (gonadotropin releasing hormone analog [GnRHa] or surgical castration) as standard of care therapy in each 28-day treatment cycle. The choice of the GnRHa (agonist or antagonist) was at discretion of the investigator. In the event of a positive result at interim or final analysis participants in treatment phase had opportunity to receive Apalutamide +ADT. Participants received treatment until radiographic progression or unequivocal clinical progression, unacceptable toxicity, or death. Participants received JNJ-56021927 (apalutamide) 240 milligrams (mg) (4*60 mg tablets) orally qd along with ADT (gonadotropin releasing hormone analog [GnRHa] or surgical castration) as standard of care therapy in each 28-day treatment cycle. The choice of the GnRHa (agonist or antagonist) was at discretion of the investigator. Participants received treatment until radiographic progression or unequivocal clinical progression, unacceptable toxicity, or death.
    Measure Participants 527 525
    Median (95% Confidence Interval) [months]
    NA
    NA
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo + Androgen Deprivation Therapy (ADT), Apalutamide + ADT
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.3608
    Comments
    Method Log Rank
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.857
    Confidence Interval (2-Sided) 95%
    0.615 to 1.194
    Parameter Dispersion Type:
    Value:
    Estimation Comments

    Adverse Events

    Time Frame Up to 57 months
    Adverse Event Reporting Description Safety Analysis set included all participants who received at least 1 dose of randomized study drug. Crossover participants were counted twice (in Placebo + ADT arm and in Placebo + ADT to Apalutamide + ADT arm) for safety analysis. For crossover participants, adverse events after initiation of crossover treatment were summarized separately in Placebo + ADT to Apalutamide + ADT arm. However, adverse events occurred before crossover treatment were summarized in Placebo + ADT arm.
    Arm/Group Title Placebo + Androgen Deprivation Therapy (ADT) Placebo + ADT to Apalutamide + ADT Apalutamide + ADT
    Arm/Group Description Participants received matching placebo (4 tablets) orally once daily (qd) along with ADT (gonadotropin releasing hormone analog [GnRHa] or surgical castration) as standard of care therapy in each 28-day treatment cycle. The choice of the GnRHa (agonist or antagonist) was at discretion of the investigator. In the event of a positive result at interim or final analysis participants in treatment phase had opportunity to receive Apalutamide +ADT. Participants received treatment until radiographic progression or unequivocal clinical progression, unacceptable toxicity, or death. After interim analysis and unblinding, participants receiving placebo +ADT crossed over to receive 240 mg apalutamide orally qd along with ADT in open-label extension phase. Participants received JNJ-56021927 (apalutamide) 240 milligrams (mg) (4*60 mg tablets) orally qd along with ADT (gonadotropin releasing hormone analog [GnRHa] or surgical castration) as standard of care therapy in each 28-day treatment cycle. The choice of the GnRHa (agonist or antagonist) was at discretion of the investigator. Participants received treatment until radiographic progression or unequivocal clinical progression, unacceptable toxicity, or death.
    All Cause Mortality
    Placebo + Androgen Deprivation Therapy (ADT) Placebo + ADT to Apalutamide + ADT Apalutamide + ADT
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 35/527 (6.6%) 10/208 (4.8%) 31/524 (5.9%)
    Serious Adverse Events
    Placebo + Androgen Deprivation Therapy (ADT) Placebo + ADT to Apalutamide + ADT Apalutamide + ADT
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 115/527 (21.8%) 29/208 (13.9%) 153/524 (29.2%)
    Blood and lymphatic system disorders
    Anaemia 6/527 (1.1%) 0/208 (0%) 1/524 (0.2%)
    Coagulopathy 0/527 (0%) 0/208 (0%) 1/524 (0.2%)
    Febrile Neutropenia 0/527 (0%) 0/208 (0%) 1/524 (0.2%)
    Thrombocytopenia 1/527 (0.2%) 0/208 (0%) 0/524 (0%)
    Cardiac disorders
    Acute Coronary Syndrome 0/527 (0%) 0/208 (0%) 1/524 (0.2%)
    Acute Myocardial Infarction 0/527 (0%) 0/208 (0%) 3/524 (0.6%)
    Angina Pectoris 2/527 (0.4%) 0/208 (0%) 3/524 (0.6%)
    Angina Unstable 1/527 (0.2%) 0/208 (0%) 0/524 (0%)
    Aortic Valve Disease Mixed 0/527 (0%) 0/208 (0%) 1/524 (0.2%)
    Arteriosclerosis Coronary Artery 0/527 (0%) 0/208 (0%) 1/524 (0.2%)
    Atrial Fibrillation 0/527 (0%) 0/208 (0%) 2/524 (0.4%)
    Atrioventricular Block Complete 0/527 (0%) 0/208 (0%) 1/524 (0.2%)
    Cardiac Amyloidosis 1/527 (0.2%) 0/208 (0%) 0/524 (0%)
    Cardiac Disorder 1/527 (0.2%) 0/208 (0%) 0/524 (0%)
    Cardiac Failure 0/527 (0%) 0/208 (0%) 1/524 (0.2%)
    Cardiac Failure Chronic 1/527 (0.2%) 0/208 (0%) 1/524 (0.2%)
    Cardiac Failure Congestive 1/527 (0.2%) 0/208 (0%) 2/524 (0.4%)
    Cor Pulmonale Chronic 0/527 (0%) 0/208 (0%) 1/524 (0.2%)
    Coronary Artery Disease 0/527 (0%) 1/208 (0.5%) 0/524 (0%)
    Coronary Artery Occlusion 0/527 (0%) 0/208 (0%) 1/524 (0.2%)
    Coronary Artery Stenosis 0/527 (0%) 0/208 (0%) 3/524 (0.6%)
    Mitral Valve Disease 0/527 (0%) 0/208 (0%) 1/524 (0.2%)
    Myocardial Infarction 0/527 (0%) 0/208 (0%) 8/524 (1.5%)
    Myocardial Ischaemia 0/527 (0%) 0/208 (0%) 1/524 (0.2%)
    Sinoatrial Block 0/527 (0%) 0/208 (0%) 1/524 (0.2%)
    Sinus Node Dysfunction 0/527 (0%) 0/208 (0%) 1/524 (0.2%)
    Supraventricular Extrasystoles 0/527 (0%) 0/208 (0%) 1/524 (0.2%)
    Supraventricular Tachycardia 1/527 (0.2%) 0/208 (0%) 0/524 (0%)
    Ventricular Fibrillation 0/527 (0%) 0/208 (0%) 1/524 (0.2%)
    Ear and labyrinth disorders
    Vertigo Positional 0/527 (0%) 0/208 (0%) 1/524 (0.2%)
    Endocrine disorders
    Goitre 0/527 (0%) 0/208 (0%) 1/524 (0.2%)
    Hyperparathyroidism 1/527 (0.2%) 0/208 (0%) 0/524 (0%)
    Eye disorders
    Cataract 0/527 (0%) 0/208 (0%) 1/524 (0.2%)
    Open Angle Glaucoma 1/527 (0.2%) 0/208 (0%) 0/524 (0%)
    Gastrointestinal disorders
    Abdominal Distension 0/527 (0%) 0/208 (0%) 1/524 (0.2%)
    Abdominal Pain Lower 0/527 (0%) 0/208 (0%) 2/524 (0.4%)
    Anal Fistula 1/527 (0.2%) 0/208 (0%) 0/524 (0%)
    Constipation 1/527 (0.2%) 0/208 (0%) 1/524 (0.2%)
    Dyschezia 1/527 (0.2%) 0/208 (0%) 0/524 (0%)
    Dysphagia 1/527 (0.2%) 0/208 (0%) 0/524 (0%)
    Gastric Ulcer Perforation 1/527 (0.2%) 0/208 (0%) 1/524 (0.2%)
    Gastritis 0/527 (0%) 0/208 (0%) 1/524 (0.2%)
    Gastrointestinal Haemorrhage 0/527 (0%) 0/208 (0%) 1/524 (0.2%)
    Haemorrhagic Erosive Gastritis 0/527 (0%) 0/208 (0%) 1/524 (0.2%)
    Inguinal Hernia 1/527 (0.2%) 0/208 (0%) 3/524 (0.6%)
    Large Intestinal Ulcer Perforation 0/527 (0%) 0/208 (0%) 1/524 (0.2%)
    Large Intestine Polyp 0/527 (0%) 1/208 (0.5%) 1/524 (0.2%)
    Nausea 0/527 (0%) 0/208 (0%) 1/524 (0.2%)
    Proctalgia 0/527 (0%) 0/208 (0%) 2/524 (0.4%)
    Terminal Ileitis 0/527 (0%) 0/208 (0%) 1/524 (0.2%)
    Umbilical Hernia 0/527 (0%) 1/208 (0.5%) 0/524 (0%)
    Vomiting 0/527 (0%) 0/208 (0%) 1/524 (0.2%)
    General disorders
    Asthenia 0/527 (0%) 0/208 (0%) 2/524 (0.4%)
    Exercise Tolerance Decreased 1/527 (0.2%) 0/208 (0%) 0/524 (0%)
    Fatigue 3/527 (0.6%) 0/208 (0%) 0/524 (0%)
    Gait Disturbance 0/527 (0%) 0/208 (0%) 1/524 (0.2%)
    General Physical Health Deterioration 0/527 (0%) 0/208 (0%) 1/524 (0.2%)
    Non-Cardiac Chest Pain 1/527 (0.2%) 2/208 (1%) 0/524 (0%)
    Oedema 0/527 (0%) 0/208 (0%) 1/524 (0.2%)
    Pain 1/527 (0.2%) 0/208 (0%) 0/524 (0%)
    Performance Status Decreased 0/527 (0%) 0/208 (0%) 1/524 (0.2%)
    Peripheral Swelling 2/527 (0.4%) 0/208 (0%) 0/524 (0%)
    Pyrexia 1/527 (0.2%) 0/208 (0%) 2/524 (0.4%)
    Hepatobiliary disorders
    Bile Duct Stone 1/527 (0.2%) 0/208 (0%) 0/524 (0%)
    Cholangiolitis 0/527 (0%) 1/208 (0.5%) 0/524 (0%)
    Cholangitis Acute 0/527 (0%) 0/208 (0%) 1/524 (0.2%)
    Cholecystitis Acute 1/527 (0.2%) 0/208 (0%) 0/524 (0%)
    Cholelithiasis 0/527 (0%) 0/208 (0%) 1/524 (0.2%)
    Hepatic Cirrhosis 0/527 (0%) 0/208 (0%) 1/524 (0.2%)
    Hepatic Failure 1/527 (0.2%) 0/208 (0%) 0/524 (0%)
    Jaundice 0/527 (0%) 0/208 (0%) 1/524 (0.2%)
    Infections and infestations
    Abdominal Abscess 1/527 (0.2%) 0/208 (0%) 0/524 (0%)
    Abscess Jaw 1/527 (0.2%) 0/208 (0%) 0/524 (0%)
    Abscess Oral 1/527 (0.2%) 0/208 (0%) 0/524 (0%)
    Bronchiolitis 1/527 (0.2%) 0/208 (0%) 0/524 (0%)
    Bronchitis 1/527 (0.2%) 1/208 (0.5%) 3/524 (0.6%)
    Cellulitis 2/527 (0.4%) 0/208 (0%) 0/524 (0%)
    Cholecystitis Infective 0/527 (0%) 0/208 (0%) 1/524 (0.2%)
    Clostridium Difficile Colitis 1/527 (0.2%) 0/208 (0%) 0/524 (0%)
    Covid-19 0/527 (0%) 1/208 (0.5%) 0/524 (0%)
    Erysipelas 0/527 (0%) 0/208 (0%) 1/524 (0.2%)
    Fournier's Gangrene 1/527 (0.2%) 0/208 (0%) 0/524 (0%)
    Infected Lymphocele 1/527 (0.2%) 0/208 (0%) 0/524 (0%)
    Influenza 2/527 (0.4%) 0/208 (0%) 0/524 (0%)
    Kidney Infection 1/527 (0.2%) 0/208 (0%) 0/524 (0%)
    Klebsiella Infection 1/527 (0.2%) 0/208 (0%) 0/524 (0%)
    Localised Infection 0/527 (0%) 0/208 (0%) 1/524 (0.2%)
    Lower Respiratory Tract Infection 1/527 (0.2%) 0/208 (0%) 0/524 (0%)
    Muscle Abscess 0/527 (0%) 0/208 (0%) 1/524 (0.2%)
    Peritonitis 1/527 (0.2%) 0/208 (0%) 1/524 (0.2%)
    Pneumonia 3/527 (0.6%) 3/208 (1.4%) 10/524 (1.9%)
    Pneumonia Bacterial 1/527 (0.2%) 0/208 (0%) 0/524 (0%)
    Pulmonary Tuberculosis 0/527 (0%) 0/208 (0%) 1/524 (0.2%)
    Pyelonephritis 0/527 (0%) 1/208 (0.5%) 0/524 (0%)
    Pyelonephritis Acute 0/527 (0%) 0/208 (0%) 2/524 (0.4%)
    Sepsis 2/527 (0.4%) 2/208 (1%) 0/524 (0%)
    Septic Shock 0/527 (0%) 0/208 (0%) 1/524 (0.2%)
    Sinusitis 1/527 (0.2%) 0/208 (0%) 0/524 (0%)
    Staphylococcal Infection 1/527 (0.2%) 0/208 (0%) 0/524 (0%)
    Tuberculosis 0/527 (0%) 1/208 (0.5%) 0/524 (0%)
    Upper Respiratory Tract Infection 0/527 (0%) 0/208 (0%) 1/524 (0.2%)
    Urinary Tract Infection 2/527 (0.4%) 1/208 (0.5%) 5/524 (1%)
    Urosepsis 1/527 (0.2%) 0/208 (0%) 5/524 (1%)
    Viral Infection 1/527 (0.2%) 0/208 (0%) 0/524 (0%)
    Viral Upper Respiratory Tract Infection 1/527 (0.2%) 0/208 (0%) 0/524 (0%)
    Injury, poisoning and procedural complications
    Acetabulum Fracture 1/527 (0.2%) 0/208 (0%) 0/524 (0%)
    Ankle Fracture 0/527 (0%) 0/208 (0%) 1/524 (0.2%)
    Brain Contusion 1/527 (0.2%) 0/208 (0%) 0/524 (0%)
    Clavicle Fracture 0/527 (0%) 0/208 (0%) 1/524 (0.2%)
    Comminuted Fracture 0/527 (0%) 0/208 (0%) 1/524 (0.2%)
    Fall 1/527 (0.2%) 0/208 (0%) 3/524 (0.6%)
    Femoral Neck Fracture 1/527 (0.2%) 0/208 (0%) 3/524 (0.6%)
    Femur Fracture 0/527 (0%) 0/208 (0%) 2/524 (0.4%)
    Forearm Fracture 0/527 (0%) 0/208 (0%) 1/524 (0.2%)
    Hand Fracture 0/527 (0%) 0/208 (0%) 1/524 (0.2%)
    Hip Fracture 0/527 (0%) 0/208 (0%) 1/524 (0.2%)
    Incisional Hernia 1/527 (0.2%) 0/208 (0%) 0/524 (0%)
    Ligament Sprain 0/527 (0%) 0/208 (0%) 1/524 (0.2%)
    Lower Limb Fracture 1/527 (0.2%) 0/208 (0%) 0/524 (0%)
    Patella Fracture 0/527 (0%) 0/208 (0%) 1/524 (0.2%)
    Radius Fracture 1/527 (0.2%) 0/208 (0%) 0/524 (0%)
    Rib Fracture 0/527 (0%) 0/208 (0%) 2/524 (0.4%)
    Skull Fracture 1/527 (0.2%) 0/208 (0%) 0/524 (0%)
    Soft Tissue Injury 1/527 (0.2%) 0/208 (0%) 0/524 (0%)
    Spinal Compression Fracture 0/527 (0%) 0/208 (0%) 4/524 (0.8%)
    Subarachnoid Haematoma 0/527 (0%) 0/208 (0%) 1/524 (0.2%)
    Subdural Haematoma 0/527 (0%) 0/208 (0%) 2/524 (0.4%)
    Subdural Haemorrhage 1/527 (0.2%) 0/208 (0%) 0/524 (0%)
    Thoracic Vertebral Fracture 0/527 (0%) 0/208 (0%) 1/524 (0.2%)
    Tibia Fracture 1/527 (0.2%) 0/208 (0%) 0/524 (0%)
    Traumatic Fracture 0/527 (0%) 0/208 (0%) 1/524 (0.2%)
    Investigations
    International Normalised Ratio Increased 0/527 (0%) 0/208 (0%) 1/524 (0.2%)
    Weight Decreased 0/527 (0%) 0/208 (0%) 1/524 (0.2%)
    Metabolism and nutrition disorders
    Dehydration 1/527 (0.2%) 1/208 (0.5%) 0/524 (0%)
    Diabetes Mellitus 0/527 (0%) 0/208 (0%) 3/524 (0.6%)
    Diabetes Mellitus Inadequate Control 1/527 (0.2%) 0/208 (0%) 1/524 (0.2%)
    Hypercalcaemia 0/527 (0%) 0/208 (0%) 1/524 (0.2%)
    Hyperglycaemia 1/527 (0.2%) 0/208 (0%) 2/524 (0.4%)
    Hyperkalaemia 0/527 (0%) 2/208 (1%) 0/524 (0%)
    Hypokalaemia 1/527 (0.2%) 0/208 (0%) 1/524 (0.2%)
    Hyponatraemia 2/527 (0.4%) 0/208 (0%) 0/524 (0%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 0/527 (0%) 0/208 (0%) 4/524 (0.8%)
    Arthropathy 0/527 (0%) 0/208 (0%) 1/524 (0.2%)
    Back Pain 6/527 (1.1%) 0/208 (0%) 4/524 (0.8%)
    Bone Pain 2/527 (0.4%) 2/208 (1%) 0/524 (0%)
    Intervertebral Disc Protrusion 1/527 (0.2%) 0/208 (0%) 1/524 (0.2%)
    Lumbar Spinal Stenosis 1/527 (0.2%) 0/208 (0%) 0/524 (0%)
    Muscular Weakness 1/527 (0.2%) 0/208 (0%) 0/524 (0%)
    Musculoskeletal Pain 1/527 (0.2%) 0/208 (0%) 1/524 (0.2%)
    Myalgia 0/527 (0%) 0/208 (0%) 1/524 (0.2%)
    Osteoarthritis 4/527 (0.8%) 1/208 (0.5%) 1/524 (0.2%)
    Osteonecrosis 1/527 (0.2%) 0/208 (0%) 0/524 (0%)
    Pain in Extremity 1/527 (0.2%) 0/208 (0%) 1/524 (0.2%)
    Pathological Fracture 4/527 (0.8%) 0/208 (0%) 2/524 (0.4%)
    Rheumatoid Arthritis 0/527 (0%) 0/208 (0%) 1/524 (0.2%)
    Rotator Cuff Syndrome 1/527 (0.2%) 0/208 (0%) 0/524 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Adenocarcinoma of Colon 0/527 (0%) 0/208 (0%) 2/524 (0.4%)
    Adrenal Neoplasm 0/527 (0%) 0/208 (0%) 1/524 (0.2%)
    Benign Lung Neoplasm 1/527 (0.2%) 0/208 (0%) 0/524 (0%)
    Bladder Cancer 1/527 (0.2%) 0/208 (0%) 1/524 (0.2%)
    Burkitt's Lymphoma 0/527 (0%) 0/208 (0%) 1/524 (0.2%)
    Cancer Pain 1/527 (0.2%) 0/208 (0%) 0/524 (0%)
    Colon Cancer 0/527 (0%) 1/208 (0.5%) 0/524 (0%)
    Gastric Cancer 1/527 (0.2%) 0/208 (0%) 1/524 (0.2%)
    Leiomyosarcoma 0/527 (0%) 0/208 (0%) 1/524 (0.2%)
    Lung Carcinoma Cell Type Unspecified Stage I 0/527 (0%) 0/208 (0%) 1/524 (0.2%)
    Lung Neoplasm Malignant 1/527 (0.2%) 0/208 (0%) 2/524 (0.4%)
    Meningioma 1/527 (0.2%) 0/208 (0%) 0/524 (0%)
    Metastases to Central Nervous System 1/527 (0.2%) 0/208 (0%) 0/524 (0%)
    Non-Small Cell Lung Cancer 1/527 (0.2%) 0/208 (0%) 0/524 (0%)
    Respiratory Papilloma 0/527 (0%) 0/208 (0%) 1/524 (0.2%)
    Squamous Cell Carcinoma 0/527 (0%) 0/208 (0%) 1/524 (0.2%)
    Nervous system disorders
    Cauda Equina Syndrome 1/527 (0.2%) 0/208 (0%) 0/524 (0%)
    Cerebral Haemorrhage 0/527 (0%) 0/208 (0%) 2/524 (0.4%)
    Cerebrovascular Accident 1/527 (0.2%) 3/208 (1.4%) 4/524 (0.8%)
    Cognitive Disorder 0/527 (0%) 0/208 (0%) 1/524 (0.2%)
    Diplegia 1/527 (0.2%) 0/208 (0%) 0/524 (0%)
    Dizziness 1/527 (0.2%) 0/208 (0%) 0/524 (0%)
    Haemorrhage Intracranial 1/527 (0.2%) 1/208 (0.5%) 1/524 (0.2%)
    Hydrocephalus 0/527 (0%) 1/208 (0.5%) 1/524 (0.2%)
    Iiird Nerve Paresis 0/527 (0%) 0/208 (0%) 1/524 (0.2%)
    Ischaemic Stroke 0/527 (0%) 0/208 (0%) 2/524 (0.4%)
    Migraine 0/527 (0%) 0/208 (0%) 1/524 (0.2%)
    Paraplegia 1/527 (0.2%) 0/208 (0%) 0/524 (0%)
    Presyncope 1/527 (0.2%) 0/208 (0%) 0/524 (0%)
    Seizure 1/527 (0.2%) 0/208 (0%) 1/524 (0.2%)
    Spinal Cord Compression 6/527 (1.1%) 0/208 (0%) 2/524 (0.4%)
    Subarachnoid Haemorrhage 0/527 (0%) 1/208 (0.5%) 2/524 (0.4%)
    Product Issues
    Device Malfunction 1/527 (0.2%) 0/208 (0%) 0/524 (0%)
    Psychiatric disorders
    Confusional State 1/527 (0.2%) 0/208 (0%) 2/524 (0.4%)
    Mental Status Changes 0/527 (0%) 0/208 (0%) 1/524 (0.2%)
    Suicidal Ideation 0/527 (0%) 0/208 (0%) 1/524 (0.2%)
    Suicide Attempt 0/527 (0%) 0/208 (0%) 1/524 (0.2%)
    Renal and urinary disorders
    Acute Kidney Injury 1/527 (0.2%) 0/208 (0%) 3/524 (0.6%)
    Bladder Perforation 1/527 (0.2%) 0/208 (0%) 0/524 (0%)
    Bladder Tamponade 1/527 (0.2%) 0/208 (0%) 0/524 (0%)
    Calculus Bladder 1/527 (0.2%) 0/208 (0%) 0/524 (0%)
    Calculus Urinary 1/527 (0.2%) 0/208 (0%) 0/524 (0%)
    Dysuria 1/527 (0.2%) 0/208 (0%) 3/524 (0.6%)
    Haematuria 3/527 (0.6%) 1/208 (0.5%) 10/524 (1.9%)
    Hydronephrosis 4/527 (0.8%) 0/208 (0%) 2/524 (0.4%)
    Nephrolithiasis 1/527 (0.2%) 0/208 (0%) 1/524 (0.2%)
    Renal Disorder 1/527 (0.2%) 0/208 (0%) 0/524 (0%)
    Renal Failure 1/527 (0.2%) 0/208 (0%) 0/524 (0%)
    Ureteric Obstruction 0/527 (0%) 0/208 (0%) 2/524 (0.4%)
    Ureterolithiasis 2/527 (0.4%) 0/208 (0%) 0/524 (0%)
    Urethral Stenosis 2/527 (0.4%) 0/208 (0%) 0/524 (0%)
    Urinary Bladder Haematoma 0/527 (0%) 0/208 (0%) 1/524 (0.2%)
    Urinary Retention 9/527 (1.7%) 0/208 (0%) 4/524 (0.8%)
    Urinary Tract Obstruction 0/527 (0%) 0/208 (0%) 3/524 (0.6%)
    Reproductive system and breast disorders
    Benign Prostatic Hyperplasia 2/527 (0.4%) 1/208 (0.5%) 2/524 (0.4%)
    Respiratory, thoracic and mediastinal disorders
    Acute Pulmonary Oedema 0/527 (0%) 0/208 (0%) 1/524 (0.2%)
    Acute Respiratory Failure 0/527 (0%) 0/208 (0%) 2/524 (0.4%)
    Chronic Obstructive Pulmonary Disease 3/527 (0.6%) 1/208 (0.5%) 3/524 (0.6%)
    Dyspnoea 2/527 (0.4%) 0/208 (0%) 0/524 (0%)
    Haemothorax 0/527 (0%) 0/208 (0%) 1/524 (0.2%)
    Hydrothorax 0/527 (0%) 0/208 (0%) 1/524 (0.2%)
    Interstitial Lung Disease 0/527 (0%) 2/208 (1%) 0/524 (0%)
    Organising Pneumonia 0/527 (0%) 0/208 (0%) 1/524 (0.2%)
    Paranasal Cyst 0/527 (0%) 0/208 (0%) 1/524 (0.2%)
    Pleural Effusion 1/527 (0.2%) 0/208 (0%) 0/524 (0%)
    Pleuritic Pain 1/527 (0.2%) 0/208 (0%) 0/524 (0%)
    Pneumonia Aspiration 0/527 (0%) 1/208 (0.5%) 0/524 (0%)
    Pneumothorax Spontaneous 0/527 (0%) 0/208 (0%) 1/524 (0.2%)
    Pulmonary Embolism 1/527 (0.2%) 0/208 (0%) 3/524 (0.6%)
    Pulmonary Haemorrhage 0/527 (0%) 0/208 (0%) 1/524 (0.2%)
    Pulmonary Mass 0/527 (0%) 1/208 (0.5%) 1/524 (0.2%)
    Pulmonary Oedema 1/527 (0.2%) 0/208 (0%) 0/524 (0%)
    Respiratory Failure 1/527 (0.2%) 2/208 (1%) 3/524 (0.6%)
    Skin and subcutaneous tissue disorders
    Drug Eruption 0/527 (0%) 0/208 (0%) 1/524 (0.2%)
    Rash 0/527 (0%) 0/208 (0%) 1/524 (0.2%)
    Vascular disorders
    Deep Vein Thrombosis 1/527 (0.2%) 0/208 (0%) 1/524 (0.2%)
    Hypertension 0/527 (0%) 1/208 (0.5%) 3/524 (0.6%)
    Venous Stenosis 0/527 (0%) 1/208 (0.5%) 0/524 (0%)
    Other (Not Including Serious) Adverse Events
    Placebo + Androgen Deprivation Therapy (ADT) Placebo + ADT to Apalutamide + ADT Apalutamide + ADT
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 485/527 (92%) 153/208 (73.6%) 494/524 (94.3%)
    Blood and lymphatic system disorders
    Anaemia 71/527 (13.5%) 13/208 (6.3%) 68/524 (13%)
    Leukopenia 21/527 (4%) 8/208 (3.8%) 29/524 (5.5%)
    Neutropenia 15/527 (2.8%) 2/208 (1%) 16/524 (3.1%)
    Thrombocytopenia 15/527 (2.8%) 6/208 (2.9%) 12/524 (2.3%)
    Endocrine disorders
    Hypothyroidism 5/527 (0.9%) 5/208 (2.4%) 23/524 (4.4%)
    Gastrointestinal disorders
    Abdominal Pain 22/527 (4.2%) 3/208 (1.4%) 17/524 (3.2%)
    Abdominal Pain Upper 13/527 (2.5%) 2/208 (1%) 17/524 (3.2%)
    Constipation 57/527 (10.8%) 6/208 (2.9%) 58/524 (11.1%)
    Diarrhoea 35/527 (6.6%) 11/208 (5.3%) 56/524 (10.7%)
    Dyspepsia 10/527 (1.9%) 2/208 (1%) 12/524 (2.3%)
    Nausea 44/527 (8.3%) 12/208 (5.8%) 41/524 (7.8%)
    Toothache 11/527 (2.1%) 1/208 (0.5%) 10/524 (1.9%)
    Vomiting 23/527 (4.4%) 3/208 (1.4%) 22/524 (4.2%)
    General disorders
    Asthenia 45/527 (8.5%) 8/208 (3.8%) 40/524 (7.6%)
    Fatigue 87/527 (16.5%) 15/208 (7.2%) 107/524 (20.4%)
    Influenza Like Illness 17/527 (3.2%) 3/208 (1.4%) 16/524 (3.1%)
    Oedema Peripheral 41/527 (7.8%) 4/208 (1.9%) 32/524 (6.1%)
    Pyrexia 16/527 (3%) 4/208 (1.9%) 15/524 (2.9%)
    Infections and infestations
    Bronchitis 12/527 (2.3%) 1/208 (0.5%) 18/524 (3.4%)
    Conjunctivitis 5/527 (0.9%) 2/208 (1%) 13/524 (2.5%)
    Herpes Zoster 11/527 (2.1%) 0/208 (0%) 10/524 (1.9%)
    Influenza 23/527 (4.4%) 5/208 (2.4%) 21/524 (4%)
    Nasopharyngitis 47/527 (8.9%) 6/208 (2.9%) 44/524 (8.4%)
    Pneumonia 14/527 (2.7%) 4/208 (1.9%) 11/524 (2.1%)
    Upper Respiratory Tract Infection 29/527 (5.5%) 6/208 (2.9%) 40/524 (7.6%)
    Urinary Tract Infection 22/527 (4.2%) 4/208 (1.9%) 28/524 (5.3%)
    Injury, poisoning and procedural complications
    Contusion 11/527 (2.1%) 4/208 (1.9%) 11/524 (2.1%)
    Fall 36/527 (6.8%) 8/208 (3.8%) 47/524 (9%)
    Rib Fracture 14/527 (2.7%) 1/208 (0.5%) 14/524 (2.7%)
    Investigations
    Alanine Aminotransferase Increased 42/527 (8%) 4/208 (1.9%) 25/524 (4.8%)
    Aspartate Aminotransferase Increased 43/527 (8.2%) 5/208 (2.4%) 18/524 (3.4%)
    Blood Alkaline Phosphatase Increased 32/527 (6.1%) 3/208 (1.4%) 18/524 (3.4%)
    Blood Lactate Dehydrogenase Increased 17/527 (3.2%) 0/208 (0%) 9/524 (1.7%)
    Blood Thyroid Stimulating Hormone Increased 2/527 (0.4%) 3/208 (1.4%) 16/524 (3.1%)
    Weight Decreased 29/527 (5.5%) 9/208 (4.3%) 43/524 (8.2%)
    Weight Increased 92/527 (17.5%) 7/208 (3.4%) 55/524 (10.5%)
    Metabolism and nutrition disorders
    Decreased Appetite 27/527 (5.1%) 11/208 (5.3%) 32/524 (6.1%)
    Hypercholesterolaemia 8/527 (1.5%) 7/208 (3.4%) 34/524 (6.5%)
    Hyperglycaemia 11/527 (2.1%) 1/208 (0.5%) 18/524 (3.4%)
    Hyperkalaemia 27/527 (5.1%) 16/208 (7.7%) 47/524 (9%)
    Hypertriglyceridaemia 13/527 (2.5%) 5/208 (2.4%) 22/524 (4.2%)
    Hyponatraemia 16/527 (3%) 2/208 (1%) 7/524 (1.3%)
    Vitamin D Deficiency 0/527 (0%) 0/208 (0%) 12/524 (2.3%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 82/527 (15.6%) 15/208 (7.2%) 101/524 (19.3%)
    Back Pain 108/527 (20.5%) 11/208 (5.3%) 106/524 (20.2%)
    Bone Pain 53/527 (10.1%) 0/208 (0%) 39/524 (7.4%)
    Groin Pain 7/527 (1.3%) 2/208 (1%) 11/524 (2.1%)
    Muscle Spasms 10/527 (1.9%) 2/208 (1%) 21/524 (4%)
    Muscular Weakness 12/527 (2.3%) 2/208 (1%) 18/524 (3.4%)
    Musculoskeletal Chest Pain 15/527 (2.8%) 2/208 (1%) 21/524 (4%)
    Musculoskeletal Pain 41/527 (7.8%) 5/208 (2.4%) 39/524 (7.4%)
    Myalgia 19/527 (3.6%) 2/208 (1%) 10/524 (1.9%)
    Osteoporosis 7/527 (1.3%) 0/208 (0%) 16/524 (3.1%)
    Pain in Extremity 67/527 (12.7%) 8/208 (3.8%) 69/524 (13.2%)
    Pathological Fracture 5/527 (0.9%) 0/208 (0%) 11/524 (2.1%)
    Spinal Pain 12/527 (2.3%) 3/208 (1.4%) 13/524 (2.5%)
    Nervous system disorders
    Dizziness 35/527 (6.6%) 7/208 (3.4%) 24/524 (4.6%)
    Dysgeusia 2/527 (0.4%) 2/208 (1%) 13/524 (2.5%)
    Headache 31/527 (5.9%) 12/208 (5.8%) 44/524 (8.4%)
    Hypoaesthesia 12/527 (2.3%) 1/208 (0.5%) 9/524 (1.7%)
    Paraesthesia 15/527 (2.8%) 0/208 (0%) 11/524 (2.1%)
    Psychiatric disorders
    Anxiety 6/527 (1.1%) 1/208 (0.5%) 11/524 (2.1%)
    Insomnia 33/527 (6.3%) 5/208 (2.4%) 28/524 (5.3%)
    Renal and urinary disorders
    Dysuria 30/527 (5.7%) 3/208 (1.4%) 35/524 (6.7%)
    Haematuria 14/527 (2.7%) 3/208 (1.4%) 21/524 (4%)
    Nocturia 15/527 (2.8%) 1/208 (0.5%) 16/524 (3.1%)
    Pollakiuria 19/527 (3.6%) 5/208 (2.4%) 21/524 (4%)
    Urinary Incontinence 8/527 (1.5%) 0/208 (0%) 14/524 (2.7%)
    Urinary Retention 14/527 (2.7%) 0/208 (0%) 13/524 (2.5%)
    Reproductive system and breast disorders
    Pelvic Pain 14/527 (2.7%) 1/208 (0.5%) 10/524 (1.9%)
    Respiratory, thoracic and mediastinal disorders
    Cough 33/527 (6.3%) 4/208 (1.9%) 40/524 (7.6%)
    Dyspnoea 15/527 (2.8%) 6/208 (2.9%) 17/524 (3.2%)
    Epistaxis 4/527 (0.8%) 2/208 (1%) 13/524 (2.5%)
    Oropharyngeal Pain 7/527 (1.3%) 1/208 (0.5%) 14/524 (2.7%)
    Skin and subcutaneous tissue disorders
    Alopecia 3/527 (0.6%) 1/208 (0.5%) 13/524 (2.5%)
    Dry Skin 8/527 (1.5%) 2/208 (1%) 18/524 (3.4%)
    Eczema 7/527 (1.3%) 4/208 (1.9%) 12/524 (2.3%)
    Erythema 2/527 (0.4%) 3/208 (1.4%) 14/524 (2.7%)
    Hyperhidrosis 10/527 (1.9%) 1/208 (0.5%) 18/524 (3.4%)
    Pruritus 25/527 (4.7%) 13/208 (6.3%) 58/524 (11.1%)
    Rash 23/527 (4.4%) 26/208 (12.5%) 106/524 (20.2%)
    Rash Maculo-Papular 5/527 (0.9%) 6/208 (2.9%) 17/524 (3.2%)
    Vascular disorders
    Hot Flush 87/527 (16.5%) 3/208 (1.4%) 121/524 (23.1%)
    Hypertension 84/527 (15.9%) 13/208 (6.3%) 100/524 (19.1%)

    Limitations/Caveats

    [Not Specified]

    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:
    NCT02489318
    Other Study ID Numbers:
    • CR107614
    • 2015-000735-32
    • 56021927PCR3002
    First Posted:
    Jul 3, 2015
    Last Update Posted:
    Aug 4, 2022
    Last Verified:
    Aug 1, 2022