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    Clinical Trial Results:
    A Phase 3, Randomized, Double-Blind Study of Nivolumab or Placebo in Combination with Docetaxel, in Men with Metastatic Castration-resistant Prostate Cancer

    Summary
    EudraCT number
    		 2019-002030-36
    Trial protocol
    		 GB   ES   DE   FR   BE   CZ   IT   RO  
    Global end of trial date
    25 Jun 2024

    Results information
    Results version number
    		 v1(current)
    This version publication date
    13 Jun 2025
    First version publication date
    13 Jun 2025
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    CA209-7DX
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT04100018
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Bristol-Myers Squibb
    Sponsor organisation address
    Chaussée de la Hulpe 185, Brussels, Belgium, 1170
    Public contact
    Global Submission Management, Clinical Trials, Bristol-Myers Squibb International Corporation, mg-gsm-ct@bms.com
    Scientific contact
    Global Submission Management, Clinical Trials, Bristol-Myers Squibb International Corporation, mg-gsm-ct@bms.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    30 Jul 2024
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    25 Jun 2024
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The purpose of this study is to assess the safety and effectiveness of nivolumab with docetaxel in men with advanced castration resistant prostate cancer who have progressed after second-generation hormonal manipulation.
    Protection of trial subjects
    The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Conference on Harmonization Good Clinical Practice Guidelines. All the local regulatory requirements pertinent to safety of trial participants were followed.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    06 Feb 2020
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Canada: 5
    Country: Number of subjects enrolled
    United States: 108
    Country: Number of subjects enrolled
    Austria: 10
    Country: Number of subjects enrolled
    Belgium: 20
    Country: Number of subjects enrolled
    Czechia: 28
    Country: Number of subjects enrolled
    France: 101
    Country: Number of subjects enrolled
    Germany: 52
    Country: Number of subjects enrolled
    Italy: 33
    Country: Number of subjects enrolled
    Poland: 40
    Country: Number of subjects enrolled
    Romania: 16
    Country: Number of subjects enrolled
    Russian Federation: 24
    Country: Number of subjects enrolled
    Spain: 77
    Country: Number of subjects enrolled
    United Kingdom: 45
    Country: Number of subjects enrolled
    China: 69
    Country: Number of subjects enrolled
    Japan: 94
    Country: Number of subjects enrolled
    Korea, Republic of: 39
    Country: Number of subjects enrolled
    Taiwan: 18
    Country: Number of subjects enrolled
    Hong Kong: 1
    Country: Number of subjects enrolled
    Singapore: 12
    Country: Number of subjects enrolled
    Argentina: 76
    Country: Number of subjects enrolled
    Australia: 32
    Country: Number of subjects enrolled
    Brazil: 70
    Country: Number of subjects enrolled
    Chile: 10
    Country: Number of subjects enrolled
    Israel: 17
    Country: Number of subjects enrolled
    Mexico: 12
    Country: Number of subjects enrolled
    New Zealand: 4
    Country: Number of subjects enrolled
    Türkiye: 17
    Worldwide total number of subjects
    1030
    EEA total number of subjects
    377
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    268
    From 65 to 84 years
    745
    85 years and over
    17

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 1030 participants were randomized.

    Period 1
    Period 1 title
    Pre-Treatment Period
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Nivolumab + Docetaxel + Prednisone
    Arm description
    		 Participants with metastatic castration resistant prostate cancer (mCRPC) who are chemotherapy-naïve for mCRPC and have received at least 1 but no more than 2 second-generation hormonal manipulations received Docetaxel 75 milligram per meter square (mg/m^2) intravenous (IV) once in a week (Q3W) + Prednisone 5 milligram (mg) orally (PO) twice a day (BID) + Nivolumab 360 mg IV Q3W for maximum 10 cycles, followed by Nivolumab 480 mg IV once in four weeks (Q4W) until disease progression or unacceptable toxicity or maximum of 2 years from the date of first dose or withdraw of consent.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Nivolumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    360 mg IV Q3W

    Investigational medicinal product name
    Docetaxel
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    75 mg/m² IV

    Investigational medicinal product name
    Prednisone
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Chewable tablet
    Routes of administration
    Oral use
    Dosage and administration details
    5 mg PO BID

    Arm title
    		 Placebo + Docetaxel + Prednisone
    Arm description
    		 Participants with metastatic castration resistant prostate cancer (mCRPC) who are chemotherapy-naïve for mCRPC and have received at least 1 but no more than 2 second-generation hormonal manipulations received Docetaxel 75 mg/m^2 IV Q3W + Prednisone 5 mg PO BID + Placebo IV Q3W for maximum 10 cycles, followed by Placebo IV Q4W until disease progression or unacceptable toxicity or maximum of 2 years from the date of first dose or withdraw of consent.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Docetaxel
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    75 mg/m² IV

    Investigational medicinal product name
    Prednisone
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Chewable tablet
    Routes of administration
    Oral use
    Dosage and administration details
    5 mg PO BID

    Number of subjects in period 1
    		Nivolumab + Docetaxel + Prednisone Placebo + Docetaxel + Prednisone
    Started
    514
    516
    Completed
    510
    510
    Not completed
    4
    6
         Participant withdrew consent
    2
    -
         Not Reported
    -
    4
         Poor/Non-compliance
    1
    -
         Subject no longer meets study criteria
    1
    1
         Participant request to discontinue study treatment
    -
    1
    Period 2
    Period 2 title
    Treatment Period
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Nivolumab + Docetaxel + Prednisone
    Arm description
    		 Participants with metastatic castration resistant prostate cancer (mCRPC) who are chemotherapy-naïve for mCRPC and have received at least 1 but no more than 2 second-generation hormonal manipulations received Docetaxel 75 milligram per meter square (mg/m^2) intravenous (IV) once in a week (Q3W) + Prednisone 5 milligram (mg) orally (PO) twice a day (BID) + Nivolumab 360 mg IV Q3W for maximum 10 cycles, followed by Nivolumab 480 mg IV once in four weeks (Q4W) until disease progression or unacceptable toxicity or maximum of 2 years from the date of first dose or withdraw of consent.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Nivolumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    360 mg IV Q3W

    Investigational medicinal product name
    Docetaxel
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    75 mg/m² IV

    Investigational medicinal product name
    Prednisone
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Chewable tablet
    Routes of administration
    Oral use
    Dosage and administration details
    5 mg PO BID

    Arm title
    		 Placebo + Docetaxel + Prednisone
    Arm description
    		 Participants with metastatic castration resistant prostate cancer (mCRPC) who are chemotherapy-naïve for mCRPC and have received at least 1 but no more than 2 second-generation hormonal manipulations received Docetaxel 75 mg/m^2 IV Q3W + Prednisone 5 mg PO BID + Placebo IV Q3W for maximum 10 cycles, followed by Placebo IV Q4W until disease progression or unacceptable toxicity or maximum of 2 years from the date of first dose or withdraw of consent.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Prednisone
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Chewable tablet
    Routes of administration
    Oral use
    Dosage and administration details
    5 mg PO BID

    Investigational medicinal product name
    Docetaxel
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    75 mg/m² IV

    Number of subjects in period 2
    		Nivolumab + Docetaxel + Prednisone Placebo + Docetaxel + Prednisone
    Started
    510
    510
    Completed
    19
    11
    Not completed
    491
    499
         Adverse event, serious fatal
    16
    11
         Participant withdrew consent
    10
    10
         Ongoing Treatment
    1
    -
         Maximum clinical benefit
    3
    -
         Other Reason
    26
    37
         Poor/Non-compliance
    1
    -
         Administrative reasons by sponsor
    16
    30
         Completed treatment as per protocol
    1
    2
         Disease Progression
    284
    327
         Adverse event, non-fatal
    14
    6
         Study drug toxicity
    67
    28
         Adverse event unrelated to study drug
    13
    12
         Lost to follow-up
    2
    2
         Lack of efficacy
    4
    2
         Participant request to discontinue study treatment
    33
    32

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Nivolumab + Docetaxel + Prednisone
    Reporting group description
    		 Participants with metastatic castration resistant prostate cancer (mCRPC) who are chemotherapy-naïve for mCRPC and have received at least 1 but no more than 2 second-generation hormonal manipulations received Docetaxel 75 milligram per meter square (mg/m^2) intravenous (IV) once in a week (Q3W) + Prednisone 5 milligram (mg) orally (PO) twice a day (BID) + Nivolumab 360 mg IV Q3W for maximum 10 cycles, followed by Nivolumab 480 mg IV once in four weeks (Q4W) until disease progression or unacceptable toxicity or maximum of 2 years from the date of first dose or withdraw of consent.

    Reporting group title
    Placebo + Docetaxel + Prednisone
    Reporting group description
    		 Participants with metastatic castration resistant prostate cancer (mCRPC) who are chemotherapy-naïve for mCRPC and have received at least 1 but no more than 2 second-generation hormonal manipulations received Docetaxel 75 mg/m^2 IV Q3W + Prednisone 5 mg PO BID + Placebo IV Q3W for maximum 10 cycles, followed by Placebo IV Q4W until disease progression or unacceptable toxicity or maximum of 2 years from the date of first dose or withdraw of consent.

    Reporting group values
    		 Nivolumab + Docetaxel + Prednisone Placebo + Docetaxel + Prednisone Total
    Number of subjects
    		 514 516 1030
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0
        Newborns (0-27 days)
    		 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0
        Children (2-11 years)
    		 0 0 0
        Adolescents (12-17 years)
    		 0 0 0
        Adults (18-64 years)
    		 139 129 268
        From 65-84 years
    		 370 375 745
        85 years and over
    		 5 12 17
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 68.9 ( 7.5 ) 69.6 ( 8.1 ) -
    Sex: Female, Male
    Units: participants
        Female
    		 0 1 1
        Male
    		 514 515 1029
    Race/Ethnicity, Customized
    Units: Subjects
        White
    		 333 329 662
        Black or African American
    		 20 15 35
        Asian
    		 35 45 80
        Native Hawaiian or other pacific islander
    		 1 0 1
        Chinese
    		 40 38 78
        Japanese
    		 33 45 78
        Asian other
    		 1 0 1
        Other
    		 30 27 57
        Not Reported
    		 19 16 35
        Asian Indian
    		 2 1 3

    End points

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    End points reporting groups
    Reporting group title
    Nivolumab + Docetaxel + Prednisone
    Reporting group description
    		 Participants with metastatic castration resistant prostate cancer (mCRPC) who are chemotherapy-naïve for mCRPC and have received at least 1 but no more than 2 second-generation hormonal manipulations received Docetaxel 75 milligram per meter square (mg/m^2) intravenous (IV) once in a week (Q3W) + Prednisone 5 milligram (mg) orally (PO) twice a day (BID) + Nivolumab 360 mg IV Q3W for maximum 10 cycles, followed by Nivolumab 480 mg IV once in four weeks (Q4W) until disease progression or unacceptable toxicity or maximum of 2 years from the date of first dose or withdraw of consent.

    Reporting group title
    Placebo + Docetaxel + Prednisone
    Reporting group description
    		 Participants with metastatic castration resistant prostate cancer (mCRPC) who are chemotherapy-naïve for mCRPC and have received at least 1 but no more than 2 second-generation hormonal manipulations received Docetaxel 75 mg/m^2 IV Q3W + Prednisone 5 mg PO BID + Placebo IV Q3W for maximum 10 cycles, followed by Placebo IV Q4W until disease progression or unacceptable toxicity or maximum of 2 years from the date of first dose or withdraw of consent.
    Reporting group title
    Nivolumab + Docetaxel + Prednisone
    Reporting group description
    		 Participants with metastatic castration resistant prostate cancer (mCRPC) who are chemotherapy-naïve for mCRPC and have received at least 1 but no more than 2 second-generation hormonal manipulations received Docetaxel 75 milligram per meter square (mg/m^2) intravenous (IV) once in a week (Q3W) + Prednisone 5 milligram (mg) orally (PO) twice a day (BID) + Nivolumab 360 mg IV Q3W for maximum 10 cycles, followed by Nivolumab 480 mg IV once in four weeks (Q4W) until disease progression or unacceptable toxicity or maximum of 2 years from the date of first dose or withdraw of consent.

    Reporting group title
    Placebo + Docetaxel + Prednisone
    Reporting group description
    		 Participants with metastatic castration resistant prostate cancer (mCRPC) who are chemotherapy-naïve for mCRPC and have received at least 1 but no more than 2 second-generation hormonal manipulations received Docetaxel 75 mg/m^2 IV Q3W + Prednisone 5 mg PO BID + Placebo IV Q3W for maximum 10 cycles, followed by Placebo IV Q4W until disease progression or unacceptable toxicity or maximum of 2 years from the date of first dose or withdraw of consent.

    Primary: Radiographic Progressive Free Survival (rPFS) assessed by Blinded Independent Central Review (BICR) per Prostate Cancer Working Group 3 (PCWG3)

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    End point title
    		 Radiographic Progressive Free Survival (rPFS) assessed by Blinded Independent Central Review (BICR) per Prostate Cancer Working Group 3 (PCWG3)
    End point description
    rPFS for randomized participants is the time between randomization and the first date of documented progression or death due to any cause, whichever occurs first. The rPFS was censored at the last radiographic tumor assessment up to the start of subsequent cancer therapy for those without progression or death. It was also censored at the date of last radiographic tumor assessment prior to the missed tumor assessments for participants who had progressive disease (PD) or death immediately after more than one consecutive missed tumor assessments. Radiographic progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeter (mm). The appearance of one or more new lesions is also considered progression.
    End point type
    Primary
    End point timeframe
    from randomization to the first date of documented progression or death due to any cause, whichever occurs first (up to approximately 31 months)
    End point values
    		 Nivolumab + Docetaxel + Prednisone Placebo + Docetaxel + Prednisone
    Number of subjects analysed
    514
    516
    Units: months
        median (confidence interval 95%)
    9.43 (8.48 to 10.32)
    8.74 (8.38 to 9.99)
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Placebo + Docetaxel + Prednisone v Nivolumab + Docetaxel + Prednisone
    Number of subjects included in analysis
    1030
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.5901 [1]
    Method
    		 Logrank
    Parameter type
    		 Cox proportional hazard
    Point estimate
    0.96
    Confidence interval
         level
    		 99%
         sides
    2-sided
         lower limit
    		 0.77
         upper limit
    		 1.19
    Notes
    [1] - Boundary for statistical significance p-value < 0.01

    Primary: Overall Survival (OS)

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    End point title
    		 Overall Survival (OS)
    End point description
    OS for all randomized participants is the time between randomization and the date of death from any cause. For participants who are alive, their survival time was censored at the last date that they were known to be alive. OS was censored for participants at the date of randomization if they had no follow-up.
    End point type
    Primary
    End point timeframe
    From randomization to the date of death from any cause (Up to approximately 31 months)
    End point values
    		 Nivolumab + Docetaxel + Prednisone Placebo + Docetaxel + Prednisone
    Number of subjects analysed
    514
    516
    Units: months
        median (confidence interval 95%)
    18.73 (16.95 to 21.03)
    18.92 (17.31 to 22.01)
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Nivolumab + Docetaxel + Prednisone v Placebo + Docetaxel + Prednisone
    Number of subjects included in analysis
    1030
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.3572 [2]
    Method
    		 Logrank
    Parameter type
    		 Cox proportional hazard
    Point estimate
    1.09
    Confidence interval
         level
    		 99.41%
         sides
    2-sided
         lower limit
    		 0.84
         upper limit
    		 1.43
    Notes
    [2] - Boundary for statistical significance p-value < 0.0059. Additional accuracy for p-value: 0.005866.

    Secondary: Time to Response (TTR) assessed by Blinded Independent Central Review (BICR) per Prostate Cancer Working Group (PCWG3)

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    End point title
    		 Time to Response (TTR) assessed by Blinded Independent Central Review (BICR) per Prostate Cancer Working Group (PCWG3)
    End point description
    Time to Response per PCWG3 (TTR-PCWG3) is the time from randomization to the date of the first documented CR or PR per PCWG3, as determined by BICR. Complete Response (CR) is defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. Partial Response (PR) is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
    End point type
    Secondary
    End point timeframe
    From randomization to the date of the first documented CR or PR (Up to approximately 52 months)
    End point values
    		 Nivolumab + Docetaxel + Prednisone Placebo + Docetaxel + Prednisone
    Number of subjects analysed
    59
    48
    Units: months
        median (full range (min-max))
    2.17 (1.4 to 7.8)
    2.20 (1.7 to 8.2)
    No statistical analyses for this end point

    Secondary: Objective Response Rate (ORR) assessed by Blinded Independent Central Review (BICR) per Prostate Cancer Working Group (PCWG3)

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    End point title
    		 Objective Response Rate (ORR) assessed by Blinded Independent Central Review (BICR) per Prostate Cancer Working Group (PCWG3)
    End point description
    Objective Response Rate per PCWG3 (ORR-PCWG3) is the percentage of participants who have a confirmed complete or partial best overall response (BOR) per PCWG3 among randomized participants who have measurable disease at baseline. Complete Response (CR) is defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. Partial Response (PR) is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Baseline was defined as evaluations or events that occur before the date and time of the first dose of study treatment or evaluations on the same date and time of the first dose of study treatment were also considered as baseline evaluations.
    End point type
    Secondary
    End point timeframe
    From date of randomization to the date of objectively documented progression per PCWG3 or the date of subsequent systemic cancer therapy, whichever occurs first (Up to approximately 52 months)
    End point values
    		 Nivolumab + Docetaxel + Prednisone Placebo + Docetaxel + Prednisone
    Number of subjects analysed
    216
    204
    Units: percentage of participants
        number (confidence interval 95%)
    27.3 (21.5 to 33.8)
    23.5 (17.9 to 30.0)
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Nivolumab + Docetaxel + Prednisone v Placebo + Docetaxel + Prednisone
    Number of subjects included in analysis
    420
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Adjusted Difference
    Point estimate
    3.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.5
         upper limit
    		 12.1

    Secondary: Duration of Response assessed by Blinded Independent Central Review (BICR) per Prostate Cancer Working Group (PCWG3)

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    End point title
    		 Duration of Response assessed by Blinded Independent Central Review (BICR) per Prostate Cancer Working Group (PCWG3)
    End point description
    Duration of Response per PCWG3 (DOR-PCWG3) is time between the date of first response (CR/PR per PCWG3) to the date of first documented radiographic progression per PCWG3,as determined by BICR, or death due to any cause whichever occurs first. Complete Response (CR) is defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. Partial Response (PR) is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Radiographic progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeter (mm). The appearance of one or more new lesions is also considered progression.
    End point type
    Secondary
    End point timeframe
    From randomization date to the date of first documented radiographic progression or death due to any cause whichever occurs first (Up to approximately 52 months)
    End point values
    		 Nivolumab + Docetaxel + Prednisone Placebo + Docetaxel + Prednisone
    Number of subjects analysed
    59
    48
    Units: months
        median (confidence interval 95%)
    8.31 (6.18 to 10.15)
    8.11 (6.34 to 8.74)
    No statistical analyses for this end point

    Secondary: Prostate-specific antigen (PSA) Response Rate (PSA-RR)

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    End point title
    		 Prostate-specific antigen (PSA) Response Rate (PSA-RR)
    End point description
    PSA Response Rate (PSA-RR) is the percentage of randomized participants with a 50% or greater decrease in PSA from baseline to the lowest post-baseline PSA result. A second consecutive value obtained 3 or more weeks later is required to confirm the PSA response. Baseline was defined as valuations or events that occur before the date and time of the first dose of study treatment or evaluations on the same date and time of the first dose of study treatment were also considered as baseline evaluations.
    End point type
    Secondary
    End point timeframe
    Up to approximately 52 months
    End point values
    		 Nivolumab + Docetaxel + Prednisone Placebo + Docetaxel + Prednisone
    Number of subjects analysed
    498
    503
    Units: percentage of participants
        number (confidence interval 95%)
    42.4 (38.0 to 46.8)
    41.6 (37.2 to 46.0)
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Nivolumab + Docetaxel + Prednisone v Placebo + Docetaxel + Prednisone
    Number of subjects included in analysis
    1001
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Percentage Difference
    Point estimate
    0.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.2
         upper limit
    		 7

    Secondary: Time to PSA Progression (TTP-PSA)

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    End point title
    		 Time to PSA Progression (TTP-PSA)
    End point description
    Time to PSA Progression (TTP-PSA) is the time between randomization to the date of PSA progression per PCWG3 in randomized participants. PSA Progression: For participants with an initial PSA decline from baseline, the date of PSA progression is the date that an increase of 25% or more and an absolute increase of 2 ng/mL or more from the nadir are documented and confirmed by a second consecutive PSA value at least 3 weeks later. For participants with no PSA decline from baseline, the date of PSA progression is date that an increase of 25% or more and an absolute increase of 2 ng/mL or more from baseline are documented at or beyond Week 13. Baseline was defined as valuations or events that occur before the date and time of the first dose of study treatment or evaluations on the same date and time of the first dose of study treatment were also considered as baseline evaluations. Censored at date of last PSA evaluation on/prior to start of subsequent cancer therapy.
    End point type
    Secondary
    End point timeframe
    from randomization to the date of PSA Progression (Up to approximately 31 months)
    End point values
    		 Nivolumab + Docetaxel + Prednisone Placebo + Docetaxel + Prednisone
    Number of subjects analysed
    514
    516
    Units: months
        median (confidence interval 95%)
    6.28 (5.82 to 6.97)
    6.21 (5.65 to 6.77)
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Nivolumab + Docetaxel + Prednisone v Placebo + Docetaxel + Prednisone
    Number of subjects included in analysis
    1030
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Cox proportional hazard
    Point estimate
    1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.86
         upper limit
    		 1.16

    Secondary: Number of Participants with Adverse Events

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    End point title
    		 Number of Participants with Adverse Events
    End point description
    An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory finding), symptom, or disease temporally associated with the use of study treatment, whether or not considered related to the study treatment.
    End point type
    Secondary
    End point timeframe
    From first dose and 30 days after last dose of study therapy (Up to approximately 25 months)
    End point values
    		 Nivolumab + Docetaxel + Prednisone Placebo + Docetaxel + Prednisone
    Number of subjects analysed
    510
    510
    Units: participants
    501
    503
    No statistical analyses for this end point

    Secondary: Number of Participants with Endocrine Immune-Mediated Adverse Events

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    End point title
    		 Number of Participants with Endocrine Immune-Mediated Adverse Events
    End point description
    Immune-mediated adverse events are AEs consistent with an immune-mediated mechanism or immune-mediated component for which non-inflammatory etiologies (eg, infection or tumor progression) have been ruled out. IMAEs can include events with an alternate etiology which were exacerbated by the induction of autoimmunity. An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory finding), symptom, or disease temporally associated with the use of study treatment, whether or not considered related to the study treatment.
    End point type
    Secondary
    End point timeframe
    From first dose and 100 days after last dose of study therapy (Up to approximately 13 months)
    End point values
    		 Nivolumab + Docetaxel + Prednisone Placebo + Docetaxel + Prednisone
    Number of subjects analysed
    510
    510
    Units: participants
        Adrenal insufficiency
    7
    4
        Hypothyroidism
    27
    11
        Thyroiditis
    1
    0
        Diabetes mellitus
    1
    2
        Diabetic ketoacidosis
    1
    0
        Type 1 diabetes mellitus
    1
    0
        Hyperthyroidism
    20
    11
        Immune-mediated hypophysitis
    1
    0
        Hypopituitarism
    0
    1
    No statistical analyses for this end point

    Secondary: Number of Participants with Serious Adverse Events

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    End point title
    		 Number of Participants with Serious Adverse Events
    End point description
    Serious Adverse Event (SAE) is defined as any untoward medical occurrence that, at any dose results in death or Is life-threatening or requires inpatient hospitalization or causes prolongation of existing hospitalization or results in persistent or significant disability/incapacity or is a congenital anomaly/birth defect.
    End point type
    Secondary
    End point timeframe
    From first dose and 30 days after last dose of study therapy (Up to approximately 25 months)
    End point values
    		 Nivolumab + Docetaxel + Prednisone Placebo + Docetaxel + Prednisone
    Number of subjects analysed
    510
    510
    Units: participants
    223
    192
    No statistical analyses for this end point

    Secondary: Number of Participants with Adverse Events Leading to Discontinuation

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    End point title
    		 Number of Participants with Adverse Events Leading to Discontinuation
    End point description
    An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory finding), symptom, or disease temporally associated with the use of study treatment, whether or not considered related to the study treatment.
    End point type
    Secondary
    End point timeframe
    From first dose and 30 days after last dose of study therapy (Up to approximately 25 months)
    End point values
    		 Nivolumab + Docetaxel + Prednisone Placebo + Docetaxel + Prednisone
    Number of subjects analysed
    510
    510
    Units: participants
    148
    101
    No statistical analyses for this end point

    Secondary: Number of Participants with Non-Endocrine Immune-Mediated Adverse Events

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    End point title
    		 Number of Participants with Non-Endocrine Immune-Mediated Adverse Events
    End point description
    Immune-mediated adverse events are AEs consistent with an immune-mediated mechanism or immune-mediated component for which non-inflammatory etiologies (eg, infection or tumor progression) have been ruled out. IMAEs can include events with an alternate etiology which were exacerbated by the induction of autoimmunity. An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory finding), symptom, or disease temporally associated with the use of study treatment, whether or not considered related to the study treatment.
    End point type
    Secondary
    End point timeframe
    From first dose and 100 days after last dose of study therapy (Up to approximately 13 months)
    End point values
    		 Nivolumab + Docetaxel + Prednisone Placebo + Docetaxel + Prednisone
    Number of subjects analysed
    510
    510
    Units: participants
        Pneumonitis
    15
    2
        Interstitial lung disease
    5
    1
        Immune-mediated lung disease
    1
    0
        Diarrhoea
    8
    2
        Colitis
    4
    0
        Enterocolitis
    1
    0
        Alanine aminotransferase increased
    5
    0
        Aspartate aminotransferase increased
    3
    0
        Hypertransaminasaemia
    3
    0
        Autoimmune hepatitis
    2
    0
        Immune-mediated hepatitis
    2
    0
        Blood bilirubin increased
    1
    0
        Cholangitis
    1
    0
        Blood creatinine increased
    1
    0
        Acute kidney injury
    0
    1
        Immune-mediated nephritis
    0
    1
        Rash
    14
    7
        Rash maculo-papular
    3
    0
        Rash pustular
    2
    0
        Dermatitis
    1
    1
        Dermatitis acneiform
    1
    0
        Drug eruption
    1
    0
        Pemphigoid
    1
    0
        Erythema multiforme
    0
    1
        Immune-mediated dermatitis
    0
    1
        Rash macular
    0
    1
        Infusion related reaction
    3
    3
        Hypersensitivity
    0
    1
        Infusion related hypersensitivity reaction
    0
    1
    No statistical analyses for this end point

    Secondary: Number of Participants with Select Adverse Events

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    End point title
    		 Number of Participants with Select Adverse Events
    End point description
    An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory finding), symptom, or disease temporally associated with the use of study treatment, whether or not considered related to the study treatment.
    End point type
    Secondary
    End point timeframe
    From first dose and 30 days after last dose of study therapy (Up to approximately 25 months)
    End point values
    		 Nivolumab + Docetaxel + Prednisone Placebo + Docetaxel + Prednisone
    Number of subjects analysed
    510
    510
    Units: participants
        Diarrhoea
    176
    159
        Colitis
    7
    2
        Enterocolitis
    2
    1
        Frequent bowel movements
    0
    1
        Alanine aminotransferase increased
    36
    14
        Aspartate aminotransferase increased
    26
    15
        Blood alkaline phosphatase increased
    23
    22
        Blood bilirubin increased
    8
    4
        Gamma-glutamyltransferase increased
    5
    3
        Hepatic cytolysis
    4
    1
        Transaminases increased
    4
    1
        Autoimmune hepatitis
    2
    0
        Cholangitis
    2
    0
        Hyperbilirubinaemia
    2
    2
        Hypertransaminasaemia
    2
    0
        Hepatic enzyme increased
    1
    2
        Hepatitis
    1
    0
        Immune-mediated hepatitis
    1
    0
        Liver injury
    1
    0
        Liver disorder
    0
    1
        Pneumonitis
    26
    6
        Interstitial lung disease
    7
    4
        Acute respiratory failure
    1
    0
        Immune-mediated lung disease
    1
    0
        Lung infiltration
    1
    0
        Idiopathic interstitial pneumonia
    0
    1
        Blood creatinine increased
    22
    7
        Acute kidney injury
    7
    9
        Renal failure
    3
    5
        Blood urea increased
    2
    2
        Immune-mediated nephritis
    0
    1
        Rash
    51
    34
        Pruritus
    47
    20
        Eczema
    10
    3
        Rash maculo-papular
    11
    6
        Dermatitis
    6
    4
        Palmar-plantar erythrodysaesthesia syndrome
    5
    22
        Urticaria
    5
    3
        Erythema
    4
    11
        Psoriasis
    4
    3
        Skin exfoliation
    4
    2
        Dermatitis acneiform
    3
    1
        Rash macular
    3
    2
        Dermatitis allergic
    2
    0
        Rash erythematous
    2
    2
        Rash pustular
    3
    0
        Vitiligo
    2
    1
        Blister
    1
    0
        Dermatitis atopic
    1
    2
        Dermatitis exfoliative
    1
    0
        Drug eruption
    1
    0
        Erythema multiforme
    1
    1
        Exfoliative rash
    1
    0
        Pemphigoid
    1
    0
        Photosensitivity reaction
    1
    0
        Rash papular
    1
    1
        Rash pruritic
    1
    0
        Immune-mediated dermatitis
    0
    1
        Infusion related reaction
    22
    27
        Hypersensitivity
    6
    4
        Anaphylactic reaction
    1
    0
        Anaphylactic shock
    1
    0
        Bronchospasm
    0
    1
        Infusion related hypersensitivity reaction
    0
    3
    No statistical analyses for this end point

    Secondary: Number of Participants who Died

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    End point title
    		 Number of Participants who Died
    End point description
    End point type
    Secondary
    End point timeframe
    Up to approximately 52 months
    End point values
    		 Nivolumab + Docetaxel + Prednisone Placebo + Docetaxel + Prednisone
    Number of subjects analysed
    510
    510
    Units: participants
    258
    227
    No statistical analyses for this end point

    Secondary: Number of Participants with Worst Common Terminology Criteria (CTC) Grade Laboratory Test Grade Change from Baseline

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    End point title
    		 Number of Participants with Worst Common Terminology Criteria (CTC) Grade Laboratory Test Grade Change from Baseline
    End point description
    The severity of laboratory test results were graded based upon the participants symptoms according to the Common Terminology Criteria for Adverse Events (CTCAE, Version 5.0); Hematology parameters were evaluated for severity according to the following scale: Grade 0 is defined as absence of an AE or within normal limits; Grade 1 = Mild - transient or mild discomfort; no medical intervention required; Grade 2 = Moderate - mild to moderate limitation in activity; Grade 3 = Severe; Grade 4 = Life threatening. Number of participants with worst grade change results to Grade 3 or Grade 4 laboratory test results is presented. E.g., the row title HEMOGLOBIN Grade 0 to Grade 3, Grade 0 is baseline and Grade 3 is post baseline.
    End point type
    Secondary
    End point timeframe
    From first dose and 30 days after last dose of study therapy (Up to approximately 25 months)
    End point values
    		 Nivolumab + Docetaxel + Prednisone Placebo + Docetaxel + Prednisone
    Number of subjects analysed
    510
    510
    Units: Participants
        HEMOGLOBIN Grade 0 to Grade 3
    5
    3
        HEMOGLOBIN Grade 0 to Grade 4
    99999
    99999
        HEMOGLOBIN Grade 1 to Grade 3
    20
    16
        HEMOGLOBIN Grade 1 to Grade 4
    99999
    99999
        HEMOGLOBIN Grade 2 to Grade 3
    11
    11
        HEMOGLOBIN Grade 2 to Grade 4
    99999
    99999
        HEMOGLOBIN Grade 3 to Grade 3
    0
    0
        HEMOGLOBIN Grade 3 to Grade 4
    99999
    99999
        PLATELET COUNT Grade 0 to Grade 3
    2
    3
        PLATELET COUNT Grade 0 to Grade 4
    0
    1
        PLATELET COUNT Grade 1 to Grade 3
    2
    1
        PLATELET COUNT Grade 1 to Grade 4
    1
    1
        PLATELET COUNT Grade 2 to Grade 3
    0
    0
        PLATELET COUNT Grade 2 to Grade 4
    0
    0
        PLATELET COUNT Grade 3 to Grade 3
    0
    0
        PLATELET COUNT Grade 3 to Grade 4
    0
    0
        PLATELET COUNT Grade 4 to Grade 3
    0
    0
        PLATELET COUNT Grade 4 to Grade 4
    0
    0
        LEUKOCYTES Grade 0 to Grade 3
    30
    28
        LEUKOCYTES Grade 0 to Grade 4
    11
    13
        LEUKOCYTES Grade 1 to Grade 3
    5
    3
        LEUKOCYTES Grade 1 to Grade 4
    1
    1
        LEUKOCYTES Grade 2 to Grade 3
    0
    1
        LEUKOCYTES Grade 2 to Grade 4
    0
    0
        LEUKOCYTES Grade 3 to Grade 3
    0
    0
        LEUKOCYTES Grade 3 to Grade 4
    0
    0
        LEUKOCYTES Grade 4 to Grade 3
    0
    0
        LEUKOCYTES Grade 4 to Grade 4
    0
    0
        LYMPHOCYTES Grade 0 to Grade 3
    22
    17
        LYMPHOCYTES Grade 0 to Grade 4
    1
    1
        LYMPHOCYTES Grade 1 to Grade 3
    24
    22
        LYMPHOCYTES Grade 1 to Grade 4
    3
    1
        LYMPHOCYTES Grade 2 to Grade 3
    19
    30
        LYMPHOCYTES Grade 2 to Grade 4
    2
    2
        LYMPHOCYTES Grade 3 to Grade 3
    10
    19
        LYMPHOCYTES Grade 3 to Grade 4
    2
    4
        LYMPHOCYTES Grade 4 to Grade 3
    0
    0
        LYMPHOCYTES Grade 4 to Grade 4
    0
    0
        ANC Grade 0 to Grade 3
    18
    16
        ANC Grade 0 to Grade 4
    44
    39
        ANC Grade 1 to Grade 3
    0
    0
        ANC Grade 1 to Grade 4
    0
    1
        ANC Grade 2 to Grade 3
    0
    1
        ANC Grade 2 to Grade 4
    0
    1
        ANC Grade 3 to Grade 3
    0
    0
        ANC Grade 3 to Grade 4
    0
    0
        ANC Grade 4 to Grade 3
    0
    0
        ANC Grade 4 to Grade 4
    0
    0
        ALP Grade 0 to Grade 3
    5
    1
        ALP Grade 0 to Grade 4
    0
    0
        ALP Grade 1 to Grade 3
    1
    1
        ALP Grade 1 to Grade 4
    0
    0
        ALP Grade 2 to Grade 3
    0
    0
        ALP Grade 2 to Grade 4
    0
    0
        ALP Grade 3 to Grade 4
    0
    0
        ALP Grade 4 to Grade 3
    0
    0
        ALP Grade 4 to Grade 4
    0
    0
        AMT Grade 0 to Grade 3
    6
    0
        AMT Grade 0 to Grade 4
    1
    0
        AMT Grade 1 to Grade 3
    1
    2
        AMT Grade 1 to Grade 4
    1
    1
        AMT Grade 2 to Grade 3
    0
    0
        AMT Grade 2 to Grade 4
    0
    0
        AMT Grade 3 to Grade 3
    0
    0
        AMT Grade 3 to Grade 4
    0
    0
        AMT Grade 4 to Grade 3
    0
    0
        AMT Grade 4 to Grade 4
    0
    0
        ALT Grade 0 to Grade 3
    7
    2
        ALT Grade 0 to Grade 4
    3
    0
        ALT Grade 1 to Grade 3
    0
    0
        ALT Grade 1 to Grade 4
    0
    0
        ALT Grade 2 to Grade 3
    0
    0
        ALT Grade 3 to Grade 3
    0
    0
        ALT Grade 4 to Grade 3
    0
    0
        ALT Grade 4 to Grade 4
    0
    0
        BILIRUBIN Grade 0 to Grade 3
    2
    1
        BILIRUBIN Grade 0 to Grade 4
    1
    0
        BILIRUBIN Grade 1 to Grade 3
    0
    0
        BILIRUBIN Grade 1 to Grade 4
    0
    0
        BILIRUBIN Grade 2 to Grade 3
    0
    0
        BILIRUBIN Grade 2 to Grade 4
    0
    0
        BILIRUBIN Grade 3 to Grade 3
    0
    0
        BILIRUBIN Grade 3 to Grade 4
    0
    0
        BILIRUBIN Grade 4 to Grade 3
    0
    0
        BILIRUBIN Grade 4 to Grade 4
    0
    0
        CREATININE Grade 0 to Grade 3
    4
    4
        CREATININE Grade 0 to Grade 4
    0
    0
        CREATININE Grade 1 to Grade 3
    1
    0
        CREATININE Grade 1 to Grade 4
    1
    0
        CREATININE Grade 2 to Grade 3
    0
    1
        CREATININE Grade 2 to Grade 4
    1
    0
        CREATININE Grade 3 to Grade 3
    0
    0
        CREATININE Grade 3 to Grade 4
    0
    0
        CREATININE Grade 4 to Grade 3
    0
    0
        CREATININE Grade 4 to Grade 4
    0
    0
        HYPERNATREMIA Grade 0 to Grade 3
    0
    0
        HYPERNATREMIA Grade 0 to Grade 4
    0
    0
        HYPERNATREMIA Grade 1 to Grade 3
    0
    0
        HYPERNATREMIA Grade 1 to Grade 4
    0
    0
        HYPERNATREMIA Grade 2 to Grade 3
    0
    0
        HYPERNATREMIA Grade 2 to Grade 4
    0
    0
        HYPERNATREMIA Grade 3 to Grade 3
    0
    0
        HYPERNATREMIA Grade 3 to Grade 4
    0
    0
        HYPERNATREMIA Grade 4 to Grade 3
    0
    0
        HYPERNATREMIA Grade 4 to Grade 4
    0
    0
        HYPONATREMIA Grade 0 to Grade 3
    5
    4
        HYPONATREMIA Grade 0 to Grade 4
    0
    1
        HYPONATREMIA Grade 1 to Grade 3
    0
    0
        HYPONATREMIA Grade 1 to Grade 4
    0
    1
        HYPONATREMIA Grade 2 to Grade 3
    0
    0
        HYPONATREMIA Grade 2 to Grade 4
    0
    0
        HYPONATREMIA Grade 3 to Grade 3
    0
    0
        HYPONATREMIA Grade 3 to Grade 4
    0
    0
        HYPONATREMIA Grade 4 to Grade 3
    0
    0
        HYPONATREMIA Grade 4 to Grade 4
    0
    0
        HYPERKALEMIA Grade 0 to Grade 3
    8
    1
        HYPERKALEMIA Grade 0 to Grade 4
    2
    1
        HYPERKALEMIA Grade 1 to Grade 3
    2
    0
        HYPERKALEMIA Grade 1 to Grade 4
    0
    1
        HYPERKALEMIA Grade 2 to Grade 3
    1
    0
        HYPERKALEMIA Grade 2 to Grade 4
    0
    0
        HYPERKALEMIA Grade 3 to Grade 3
    0
    0
        HYPERKALEMIA Grade 3 to Grade 4
    0
    0
        HYPERKALEMIA Grade 4 to Grade 3
    0
    0
        HYPERKALEMIA Grade 4 to Grade 4
    0
    0
        HYPOKALEMIA Grade 0 to Grade 3
    7
    8
        HYPOKALEMIA Grade 0 to Grade 4
    1
    0
        HYPOKALEMIA Grade 1 to Grade 3
    3
    1
        HYPOKALEMIA Grade 1 to Grade 4
    0
    0
        HYPOKALEMIA Grade 2 to Grade 3
    0
    0
        HYPOKALEMIA Grade 2 to Grade 4
    0
    0
        HYPOKALEMIA Grade 3 to Grade 3
    0
    0
        HYPOKALEMIA Grade 3 to Grade 4
    0
    0
        HYPOKALEMIA Grade 4 to Grade 3
    0
    0
        HYPOKALEMIA Grade 4 to Grade 4
    0
    0
        HYPERCALCEMIA Grade 0 to Grade 3
    0
    0
        HYPERCALCEMIA Grade 0 to Grade 4
    0
    0
        HYPERCALCEMIA Grade 1 to Grade 3
    0
    0
        HYPERCALCEMIA Grade 1 to Grade 4
    1
    0
        HYPERCALCEMIA Grade 2 to Grade 3
    0
    0
        HYPERCALCEMIA Grade 2 to Grade 4
    0
    0
        HYPERCALCEMIA Grade 3 to Grade 3
    0
    0
        HYPERCALCEMIA Grade 3 to Grade 4
    0
    0
        HYPERCALCEMIA Grade 4 to Grade 3
    0
    0
        HYPERCALCEMIA Grade 4 to Grade 4
    0
    0
        HYPOCALCEMIA Grade 0 to Grade 3
    6
    4
        HYPOCALCEMIA Grade 0 to Grade 4
    1
    0
        HYPOCALCEMIA Grade 1 to Grade 3
    1
    2
        HYPOCALCEMIA Grade 1 to Grade 4
    0
    0
        HYPOCALCEMIA Grade 2 to Grade 3
    3
    0
        HYPOCALCEMIA Grade 2 to Grade 4
    3
    0
        HYPOCALCEMIA Grade 3 to Grade 3
    0
    0
        HYPOCALCEMIA Grade 3 to Grade 4
    0
    0
        HYPOCALCEMIA Grade 4 to Grade 3
    0
    0
        HYPOCALCEMIA Grade 4 to Grade 4
    0
    0
        HYPERMAGNESEMIA Grade 0 to Grade 3
    4
    3
        HYPERMAGNESEMIA Grade 0 to Grade 4
    0
    0
        HYPERMAGNESEMIA Grade 1 to Grade 3
    1
    0
        HYPERMAGNESEMIA Grade 1 to Grade 4
    0
    0
        HYPERMAGNESEMIA Grade 2 to Grade 3
    0
    0
        HYPERMAGNESEMIA Grade 2 to Grade 4
    0
    0
        HYPERMAGNESEMIA Grade 3 to Grade 3
    1
    0
        HYPERMAGNESEMIA Grade 3 to Grade 4
    0
    0
        HYPERMAGNESEMIA Grade 4 to Grade 3
    0
    0
        HYPERMAGNESEMIA Grade 4 to Grade 4
    0
    0
        HYPOMAGNESEMIA Grade 0 to Grade 3
    0
    0
        HYPOMAGNESEMIA Grade 0 to Grade 4
    0
    0
        HYPOMAGNESEMIA Grade 1 to Grade 3
    0
    0
        HYPOMAGNESEMIA Grade 1 to Grade 4
    0
    0
        HYPOMAGNESEMIA Grade 2 to Grade 3
    0
    0
        HYPOMAGNESEMIA Grade 2 to Grade 4
    0
    0
        HYPOMAGNESEMIA Grade 3 to Grade 3
    0
    0
        HYPOMAGNESEMIA Grade 3 to Grade 4
    0
    0
        HYPOMAGNESEMIA Grade 4 to Grade 3
    0
    0
        HYPOMAGNESEMIA Grade 4 to Grade 4
    0
    0
        HYPOGLYCEMIA Grade 0 to Grade 3
    1
    1
        HYPOGLYCEMIA Grade 0 to Grade 4
    1
    0
        HYPOGLYCEMIA Grade 1 to Grade 3
    0
    0
        HYPOGLYCEMIA Grade 1 to Grade 4
    0
    0
        HYPOGLYCEMIA Grade 2 to Grade 3
    0
    0
        HYPOGLYCEMIA Grade 2 to Grade 4
    0
    0
        HYPOGLYCEMIA Grade 3 to Grade 3
    0
    0
        HYPOGLYCEMIA Grade 3 to Grade 4
    0
    0
        HYPOGLYCEMIA Grade 4 to Grade 3
    0
    0
        HYPOGLYCEMIA Grade 4 to Grade 4
    0
    0
    No statistical analyses for this end point

    Secondary: Number of Participants with Laboratory Abnormalities in Specific Thyroid Tests

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    End point title
    		 Number of Participants with Laboratory Abnormalities in Specific Thyroid Tests
    End point description
    Blood samples were collected for conducting specific thyroid test. Baseline is defined as evaluations or events that occur before the date and time of the first dose of study treatment. Baseline was defined as evaluations or events that occur before the date and time of the first dose of study treatment or evaluations on the same date and time of the first dose of study treatment were also considered as baseline evaluations.
    End point type
    Secondary
    End point timeframe
    From first dose and 30 days after last dose of study therapy (Up to approximately 11 months)
    End point values
    		 Nivolumab + Docetaxel + Prednisone Placebo + Docetaxel + Prednisone
    Number of subjects analysed
    499
    502
    Units: participants
        TSH > (Upper Limit of Normal) ULN
    94
    77
        TSH > ULN with TSH <= ULN
    79
    54
        TSH > ULN with at Least One FT3/FT4 < LLN
    39
    20
        TSH > ULN With All Other FT3/FT4 >= LLN
    65
    52
        TSH > ULN with FT3/FT4 Test Missing
    22
    23
        TSH < Lower Limit of Normal (LLN)
    155
    124
        TSH < LLN with TSH >= LLN at Baseline
    126
    98
        TSH < LLN with at Least One FT3/FT4 > ULN
    33
    14
        TSH < LLN with all other FT3/FT4 <= ULN
    116
    106
        TSH < LLN with FT3/FT4 Test Missing
    45
    24
    No statistical analyses for this end point

    Secondary: Time to Pain Progression as assessed by Brief Pain Inventory-Short Form (BPI-SF)

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    End point title
    		 Time to Pain Progression as assessed by Brief Pain Inventory-Short Form (BPI-SF)
    End point description
    The BPI-SF is an instrument to assess pain and includes severity and interference scores. BPI-SF is an 11-item self-report questionnaire designed to assess severity and impact of pain on daily function. Participants rate severity of pain at its “worst,” “least,” and “average” in last 24 hours using an 11-point numerical rating scale with anchors of “no pain” and “pain as bad. The participant’s assessment of pain with BPI-SF Item number 3 (pain symptoms at their worst over the last 24 hours) form basis for analysis. Time to pain progression is time between date of randomization and date of first increase in worst pain intensity. Pain progression occurred if an increase in worst pain intensity of >= 2 points is observed from baseline and maintained over 2 consecutive time periods. Baseline was evaluations or events that occur before date and time of first dose of study treatment or evaluations on same date and time of first dose of study treatment were also considered as baseline.
    End point type
    Secondary
    End point timeframe
    From randomization to 1st pain symptoms at their worst over the last 24 hours (Up to approximately 31 months
    End point values
    		 Nivolumab + Docetaxel + Prednisone Placebo + Docetaxel + Prednisone
    Number of subjects analysed
    514
    516
    Units: months
        median (confidence interval 95%)
    11.53 (10.28 to 13.57)
    12.42 (11.07 to 13.63)
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    All cause mortality was collected from randomization till death (up to approximately 52 months), Serious adverse events and non-serious adverse events were collected from first dose till 100 days post last dose (Up to approximately 27 months).
    Adverse event reporting additional description
    The number at risk for All-Cause mortality represents all randomized participants. The number at risk for serious adverse events and Other (Not Including Serious) adverse events represents all participants that received at least 1 dose of study medication.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    27.0
    Reporting groups
    Reporting group title
    Nivolumab + Docetaxel + Prednisone
    Reporting group description
    		 Participants with metastatic castration resistant prostate cancer (mCRPC) who are chemotherapy-naïve for mCRPC and have received at least 1 but no more than 2 second-generation hormonal manipulations received Docetaxel 75 milligram per meter square (mg/m^2) intravenous (IV) once in a week (Q3W) + Prednisone 5 milligram (mg) orally (PO) twice a day (BID) + Nivolumab 360 mg IV Q3W for maximum 10 cycles, followed by Nivolumab 480 mg IV once in four weeks (Q4W) until disease progression or unacceptable toxicity or maximum of 2 years from the date of first dose or withdraw of consent.

    Reporting group title
    Placebo + Docetaxel + Prednisone
    Reporting group description
    		 Participants with metastatic castration resistant prostate cancer (mCRPC) who are chemotherapy-naïve for mCRPC and have received at least 1 but no more than 2 second-generation hormonal manipulations received Docetaxel 75 mg/m^2 IV Q3W + Prednisone 5 mg PO BID + Placebo IV Q3W for maximum 10 cycles, followed by Placebo IV Q4W until disease progression or unacceptable toxicity or maximum of 2 years from the date of first dose or withdraw of consent.

    Serious adverse events
    		 Nivolumab + Docetaxel + Prednisone Placebo + Docetaxel + Prednisone
    Total subjects affected by serious adverse events
         subjects affected / exposed
    256 / 510 (50.20%)
    242 / 510 (47.45%)
         number of deaths (all causes)
    258
    227
         number of deaths resulting from adverse events
    79
    76
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Brain cancer metastatic
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Acute myeloid leukaemia
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bladder cancer
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bladder transitional cell carcinoma
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchial neoplasm
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tumour pain
         subjects affected / exposed
    0 / 510 (0.00%)
    2 / 510 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colorectal cancer
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ependymoma
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malignant neoplasm progression
         subjects affected / exposed
    19 / 510 (3.73%)
    27 / 510 (5.29%)
         occurrences causally related to treatment / all
    0 / 19
    0 / 27
         deaths causally related to treatment / all
    0 / 18
    0 / 22
    Metastases to central nervous system
         subjects affected / exposed
    0 / 510 (0.00%)
    2 / 510 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metastases to meninges
         subjects affected / exposed
    2 / 510 (0.39%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Metastases to spine
         subjects affected / exposed
    0 / 510 (0.00%)
    2 / 510 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metastatic neoplasm
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Neoplasm malignant
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Neuroendocrine carcinoma of the skin
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Papillary thyroid cancer
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Prostate cancer
         subjects affected / exposed
    10 / 510 (1.96%)
    13 / 510 (2.55%)
         occurrences causally related to treatment / all
    0 / 10
    0 / 13
         deaths causally related to treatment / all
    0 / 10
    0 / 12
    Squamous cell carcinoma of lung
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tongue neoplasm
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tumour associated fever
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cancer pain
         subjects affected / exposed
    3 / 510 (0.59%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Vascular disorders
    Deep vein thrombosis
         subjects affected / exposed
    3 / 510 (0.59%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aortic dissection
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematoma
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertension
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Embolism
         subjects affected / exposed
    3 / 510 (0.59%)
    3 / 510 (0.59%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Hypotension
         subjects affected / exposed
    1 / 510 (0.20%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypovolaemic shock
         subjects affected / exposed
    1 / 510 (0.20%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Venous thrombosis limb
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Peripheral arterial occlusive disease
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral ischaemia
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thrombophlebitis
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Disease progression
         subjects affected / exposed
    2 / 510 (0.39%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 2
    0 / 1
    Asthenia
         subjects affected / exposed
    3 / 510 (0.59%)
    5 / 510 (0.98%)
         occurrences causally related to treatment / all
    1 / 3
    2 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chest discomfort
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chest pain
         subjects affected / exposed
    1 / 510 (0.20%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Death
         subjects affected / exposed
    9 / 510 (1.76%)
    4 / 510 (0.78%)
         occurrences causally related to treatment / all
    0 / 9
    0 / 4
         deaths causally related to treatment / all
    0 / 9
    0 / 4
    Fatigue
         subjects affected / exposed
    2 / 510 (0.39%)
    3 / 510 (0.59%)
         occurrences causally related to treatment / all
    2 / 2
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malaise
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mucosal inflammation
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Multiple organ dysfunction syndrome
         subjects affected / exposed
    2 / 510 (0.39%)
    2 / 510 (0.39%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 2
         deaths causally related to treatment / all
    1 / 1
    0 / 2
    Oedema peripheral
         subjects affected / exposed
    1 / 510 (0.20%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pain
         subjects affected / exposed
    3 / 510 (0.59%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Performance status decreased
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    7 / 510 (1.37%)
    3 / 510 (0.59%)
         occurrences causally related to treatment / all
    3 / 7
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sudden death
         subjects affected / exposed
    2 / 510 (0.39%)
    4 / 510 (0.78%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 2
    0 / 4
    General physical health deterioration
         subjects affected / exposed
    3 / 510 (0.59%)
    8 / 510 (1.57%)
         occurrences causally related to treatment / all
    0 / 5
    1 / 9
         deaths causally related to treatment / all
    0 / 2
    0 / 2
    Immune system disorders
    Anaphylactic shock
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Pelvic pain
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Prostatitis
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Interstitial lung disease
         subjects affected / exposed
    5 / 510 (0.98%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    5 / 5
    1 / 1
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Immune-mediated lung disease
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Epistaxis
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    4 / 510 (0.78%)
    7 / 510 (1.37%)
         occurrences causally related to treatment / all
    3 / 4
    5 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Cough
         subjects affected / exposed
    1 / 510 (0.20%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    2 / 510 (0.39%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    2 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung infiltration
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory tract haemorrhage
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    1 / 510 (0.20%)
    3 / 510 (0.59%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 2
    Pulmonary oedema
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    6 / 510 (1.18%)
    8 / 510 (1.57%)
         occurrences causally related to treatment / all
    1 / 6
    3 / 8
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Pneumothorax
         subjects affected / exposed
    1 / 510 (0.20%)
    2 / 510 (0.39%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonitis
         subjects affected / exposed
    13 / 510 (2.55%)
    3 / 510 (0.59%)
         occurrences causally related to treatment / all
    13 / 14
    3 / 3
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Psychiatric disorders
    Delirium
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Adjustment disorder with anxiety
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anxiety
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Confusional state
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mental disorder
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Product issues
    Device dislocation
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Device occlusion
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Needle issue
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aspartate aminotransferase increased
         subjects affected / exposed
    2 / 510 (0.39%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood creatine phosphokinase increased
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood creatinine increased
         subjects affected / exposed
    2 / 510 (0.39%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eastern Cooperative Oncology Group performance status worsened
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General physical condition abnormal
         subjects affected / exposed
    1 / 510 (0.20%)
    3 / 510 (0.59%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatitis B DNA assay positive
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neutrophil count decreased
         subjects affected / exposed
    1 / 510 (0.20%)
    2 / 510 (0.39%)
         occurrences causally related to treatment / all
    1 / 1
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Platelet count decreased
         subjects affected / exposed
    1 / 510 (0.20%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Weight decreased
         subjects affected / exposed
    1 / 510 (0.20%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    White blood cell count decreased
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Ankle fracture
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acetabulum fracture
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fall
         subjects affected / exposed
    1 / 510 (0.20%)
    2 / 510 (0.39%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chemical peritonitis
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Concussion
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Femoral neck fracture
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Femur fracture
         subjects affected / exposed
    2 / 510 (0.39%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hip fracture
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infusion related reaction
         subjects affected / exposed
    0 / 510 (0.00%)
    2 / 510 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Limb injury
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lumbar vertebral fracture
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Muscle rupture
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pelvic fracture
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rib fracture
         subjects affected / exposed
    1 / 510 (0.20%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Road traffic accident
         subjects affected / exposed
    2 / 510 (0.39%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Skin laceration
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal compression fracture
         subjects affected / exposed
    0 / 510 (0.00%)
    2 / 510 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal cord injury
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal fracture
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subdural haematoma
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Wound dehiscence
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thoracic vertebral fracture
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Acute myocardial infarction
         subjects affected / exposed
    1 / 510 (0.20%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Angina unstable
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arrhythmia
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardio-respiratory arrest
         subjects affected / exposed
    3 / 510 (0.59%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 3
    0 / 1
    Atrial flutter
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrioventricular block complete
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac arrest
         subjects affected / exposed
    0 / 510 (0.00%)
    3 / 510 (0.59%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 3
    Cardiac failure
         subjects affected / exposed
    1 / 510 (0.20%)
    5 / 510 (0.98%)
         occurrences causally related to treatment / all
    0 / 1
    4 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 3
    Cardiac failure congestive
         subjects affected / exposed
    2 / 510 (0.39%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    3 / 510 (0.59%)
    2 / 510 (0.39%)
         occurrences causally related to treatment / all
    1 / 4
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiogenic shock
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Left ventricular dysfunction
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Myocardial ischaemia
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myocarditis
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Supraventricular tachycardia
         subjects affected / exposed
    1 / 510 (0.20%)
    2 / 510 (0.39%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune-mediated myocarditis
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Nervous system disorders
    Hemiparesis
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Headache
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Loss of consciousness
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Malignant spinal cord compression
         subjects affected / exposed
    1 / 510 (0.20%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Amnesia
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Balance disorder
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Basal ganglia stroke
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cauda equina syndrome
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Central nervous system lesion
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebral haemorrhage
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebral infarction
         subjects affected / exposed
    1 / 510 (0.20%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    5 / 510 (0.98%)
    2 / 510 (0.39%)
         occurrences causally related to treatment / all
    1 / 5
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Cognitive disorder
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dizziness
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Embolic stroke
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Guillain-Barre syndrome
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nerve compression
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neuropathy peripheral
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral sensory neuropathy
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Presyncope
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Radiculopathy
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal cord compression
         subjects affected / exposed
    6 / 510 (1.18%)
    6 / 510 (1.18%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Superior sagittal sinus thrombosis
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Syncope
         subjects affected / exposed
    2 / 510 (0.39%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neuralgia
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    6 / 510 (1.18%)
    12 / 510 (2.35%)
         occurrences causally related to treatment / all
    4 / 8
    8 / 14
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Blood disorder
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Bone marrow infiltration
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lymphadenitis
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Febrile bone marrow aplasia
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Febrile neutropenia
         subjects affected / exposed
    17 / 510 (3.33%)
    14 / 510 (2.75%)
         occurrences causally related to treatment / all
    16 / 18
    10 / 16
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Leukopenia
         subjects affected / exposed
    1 / 510 (0.20%)
    3 / 510 (0.59%)
         occurrences causally related to treatment / all
    1 / 1
    3 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Disseminated intravascular coagulation
         subjects affected / exposed
    1 / 510 (0.20%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myelosuppression
         subjects affected / exposed
    1 / 510 (0.20%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    1 / 1
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neutropenia
         subjects affected / exposed
    9 / 510 (1.76%)
    10 / 510 (1.96%)
         occurrences causally related to treatment / all
    9 / 9
    13 / 13
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    1 / 510 (0.20%)
    3 / 510 (0.59%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eye disorders
    Cataract
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Colitis
         subjects affected / exposed
    4 / 510 (0.78%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    3 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal pain
         subjects affected / exposed
    1 / 510 (0.20%)
    2 / 510 (0.39%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal pain upper
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anal fistula
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    2 / 510 (0.39%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    1 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Large intestine perforation
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    12 / 510 (2.35%)
    9 / 510 (1.76%)
         occurrences causally related to treatment / all
    11 / 12
    7 / 9
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Diverticulum
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Duodenal ulcer
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Duodenal ulcer haemorrhage
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dysphagia
         subjects affected / exposed
    1 / 510 (0.20%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Enterocolitis
         subjects affected / exposed
    2 / 510 (0.39%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastric ulcer
         subjects affected / exposed
    0 / 510 (0.00%)
    2 / 510 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal inflammation
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal necrosis
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ileus paralytic
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Inguinal hernia
         subjects affected / exposed
    1 / 510 (0.20%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal ischaemia
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal obstruction
         subjects affected / exposed
    1 / 510 (0.20%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Cyclic vomiting syndrome
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Large intestine polyp
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 510 (0.20%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Nausea
         subjects affected / exposed
    2 / 510 (0.39%)
    3 / 510 (0.59%)
         occurrences causally related to treatment / all
    0 / 2
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oesophagitis haemorrhagic
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatitis
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatitis acute
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peptic ulcer haemorrhage
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rectal haemorrhage
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subileus
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper gastrointestinal haemorrhage
         subjects affected / exposed
    2 / 510 (0.39%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    1 / 510 (0.20%)
    3 / 510 (0.59%)
         occurrences causally related to treatment / all
    0 / 1
    2 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Leukoplakia oral
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Hepatic function abnormal
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute cholecystitis necrotic
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Autoimmune hepatitis
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Biliary dilatation
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholangitis
         subjects affected / exposed
    2 / 510 (0.39%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholecystitis acute
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatitis toxic
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune-mediated hepatitis
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Liver injury
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperbilirubinaemia
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Skin ulcer
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin disorder
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pemphigoid
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    4 / 510 (0.78%)
    5 / 510 (0.98%)
         occurrences causally related to treatment / all
    2 / 4
    1 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Calculus bladder
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Calculus urethral
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic kidney disease
         subjects affected / exposed
    2 / 510 (0.39%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dysuria
         subjects affected / exposed
    2 / 510 (0.39%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematuria
         subjects affected / exposed
    13 / 510 (2.55%)
    2 / 510 (0.39%)
         occurrences causally related to treatment / all
    0 / 19
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Hydronephrosis
         subjects affected / exposed
    0 / 510 (0.00%)
    2 / 510 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune-mediated nephritis
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nephritis
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nephrolithiasis
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal colic
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal failure
         subjects affected / exposed
    0 / 510 (0.00%)
    2 / 510 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urethral obstruction
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract obstruction
         subjects affected / exposed
    2 / 510 (0.39%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract inflammation
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary retention
         subjects affected / exposed
    2 / 510 (0.39%)
    4 / 510 (0.78%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endocrine disorders
    Adrenal insufficiency
         subjects affected / exposed
    2 / 510 (0.39%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    2 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperthyroidism
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypothyroidism
         subjects affected / exposed
    1 / 510 (0.20%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune-mediated hypophysitis
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Inappropriate antidiuretic hormone secretion
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Muscle spasms
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arthralgia
         subjects affected / exposed
    1 / 510 (0.20%)
    4 / 510 (0.78%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Back pain
         subjects affected / exposed
    3 / 510 (0.59%)
    8 / 510 (1.57%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bone pain
         subjects affected / exposed
    3 / 510 (0.59%)
    5 / 510 (0.98%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Flank pain
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune-mediated arthritis
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune-mediated myositis
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intervertebral disc protrusion
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Muscular weakness
         subjects affected / exposed
    3 / 510 (0.59%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myalgia
         subjects affected / exposed
    1 / 510 (0.20%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myositis
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteonecrosis
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteonecrosis of jaw
         subjects affected / exposed
    1 / 510 (0.20%)
    2 / 510 (0.39%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteoporosis
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pain in extremity
         subjects affected / exposed
    2 / 510 (0.39%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pain in jaw
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pathological fracture
         subjects affected / exposed
    1 / 510 (0.20%)
    4 / 510 (0.78%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rhabdomyolysis
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sacral pain
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal pain
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal pain
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Cellulitis streptococcal
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal infection
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abscess limb
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anal abscess
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Appendicitis
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atypical pneumonia
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bacteraemia
         subjects affected / exposed
    1 / 510 (0.20%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bone abscess
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchiolitis
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    1 / 510 (0.20%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    COVID-19
         subjects affected / exposed
    11 / 510 (2.16%)
    13 / 510 (2.55%)
         occurrences causally related to treatment / all
    0 / 11
    0 / 13
         deaths causally related to treatment / all
    0 / 1
    0 / 2
    COVID-19 pneumonia
         subjects affected / exposed
    2 / 510 (0.39%)
    3 / 510 (0.59%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Cellulitis
         subjects affected / exposed
    4 / 510 (0.78%)
    2 / 510 (0.39%)
         occurrences causally related to treatment / all
    2 / 4
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coronavirus infection
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Meningitis
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Device related infection
         subjects affected / exposed
    0 / 510 (0.00%)
    2 / 510 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Device related sepsis
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diarrhoea infectious
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    3 / 510 (0.59%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    2 / 3
    0 / 1
         deaths causally related to treatment / all
    2 / 2
    0 / 0
    Diverticulitis intestinal perforated
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Febrile infection
         subjects affected / exposed
    1 / 510 (0.20%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    3 / 510 (0.59%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal infection
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infection
         subjects affected / exposed
    0 / 510 (0.00%)
    2 / 510 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    1 / 510 (0.20%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intervertebral discitis
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Klebsiella urinary tract infection
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Liver abscess
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower respiratory tract infection
         subjects affected / exposed
    2 / 510 (0.39%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Lung abscess
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cystitis
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neutropenic sepsis
         subjects affected / exposed
    4 / 510 (0.78%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    4 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Scrotal infection
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteomyelitis
         subjects affected / exposed
    1 / 510 (0.20%)
    2 / 510 (0.39%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Perineal abscess
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peritonitis
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Pneumocystis jirovecii pneumonia
         subjects affected / exposed
    2 / 510 (0.39%)
    2 / 510 (0.39%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    Pneumonia
         subjects affected / exposed
    18 / 510 (3.53%)
    8 / 510 (1.57%)
         occurrences causally related to treatment / all
    9 / 18
    3 / 9
         deaths causally related to treatment / all
    2 / 4
    0 / 1
    Pneumonia aspiration
         subjects affected / exposed
    1 / 510 (0.20%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Pneumonia bacterial
         subjects affected / exposed
    3 / 510 (0.59%)
    2 / 510 (0.39%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    Post procedural infection
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Postoperative wound infection
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psoas abscess
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary sepsis
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal abscess
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory syncytial virus infection
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory tract infection
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Scrotal abscess
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oral candidiasis
         subjects affected / exposed
    1 / 510 (0.20%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    7 / 510 (1.37%)
    10 / 510 (1.96%)
         occurrences causally related to treatment / all
    3 / 7
    3 / 11
         deaths causally related to treatment / all
    3 / 4
    0 / 1
    Sinusitis
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Soft tissue infection
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal cord infection
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Staphylococcal bacteraemia
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Staphylococcal infection
         subjects affected / exposed
    0 / 510 (0.00%)
    2 / 510 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Staphylococcal sepsis
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Streptococcal infection
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tuberculosis
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    8 / 510 (1.57%)
    10 / 510 (1.96%)
         occurrences causally related to treatment / all
    0 / 9
    0 / 13
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Urosepsis
         subjects affected / exposed
    2 / 510 (0.39%)
    2 / 510 (0.39%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 2
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Vascular device infection
         subjects affected / exposed
    1 / 510 (0.20%)
    2 / 510 (0.39%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wound infection staphylococcal
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    0 / 510 (0.00%)
    5 / 510 (0.98%)
         occurrences causally related to treatment / all
    0 / 0
    4 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Metabolism and nutrition disorders
    Diabetic ketoacidosis
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Decreased appetite
         subjects affected / exposed
    3 / 510 (0.59%)
    2 / 510 (0.39%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dehydration
         subjects affected / exposed
    2 / 510 (0.39%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetes mellitus
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Failure to thrive
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperglycaemia
         subjects affected / exposed
    0 / 510 (0.00%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypernatraemia
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypokalaemia
         subjects affected / exposed
    1 / 510 (0.20%)
    1 / 510 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    1 / 510 (0.20%)
    4 / 510 (0.78%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ketoacidosis
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malnutrition
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Type 2 diabetes mellitus
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypercalcaemia
         subjects affected / exposed
    1 / 510 (0.20%)
    0 / 510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Nivolumab + Docetaxel + Prednisone Placebo + Docetaxel + Prednisone
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    479 / 510 (93.92%)
    494 / 510 (96.86%)
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    113 / 510 (22.16%)
    108 / 510 (21.18%)
         occurrences all number
    183
    148
    Fatigue
         subjects affected / exposed
    141 / 510 (27.65%)
    149 / 510 (29.22%)
         occurrences all number
    171
    175
    Pyrexia
         subjects affected / exposed
    41 / 510 (8.04%)
    54 / 510 (10.59%)
         occurrences all number
    57
    69
    Pain
         subjects affected / exposed
    24 / 510 (4.71%)
    26 / 510 (5.10%)
         occurrences all number
    27
    27
    Oedema peripheral
         subjects affected / exposed
    90 / 510 (17.65%)
    108 / 510 (21.18%)
         occurrences all number
    94
    119
    Mucosal inflammation
         subjects affected / exposed
    20 / 510 (3.92%)
    30 / 510 (5.88%)
         occurrences all number
    36
    35
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    51 / 510 (10.00%)
    49 / 510 (9.61%)
         occurrences all number
    58
    51
    Dyspnoea
         subjects affected / exposed
    52 / 510 (10.20%)
    38 / 510 (7.45%)
         occurrences all number
    56
    45
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    35 / 510 (6.86%)
    47 / 510 (9.22%)
         occurrences all number
    36
    53
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    38 / 510 (7.45%)
    16 / 510 (3.14%)
         occurrences all number
    44
    22
    Aspartate aminotransferase increased
         subjects affected / exposed
    27 / 510 (5.29%)
    20 / 510 (3.92%)
         occurrences all number
    32
    23
    Neutrophil count decreased
         subjects affected / exposed
    47 / 510 (9.22%)
    46 / 510 (9.02%)
         occurrences all number
    119
    75
    Weight decreased
         subjects affected / exposed
    42 / 510 (8.24%)
    42 / 510 (8.24%)
         occurrences all number
    43
    46
    White blood cell count decreased
         subjects affected / exposed
    33 / 510 (6.47%)
    39 / 510 (7.65%)
         occurrences all number
    99
    65
    Injury, poisoning and procedural complications
    Infusion related reaction
         subjects affected / exposed
    22 / 510 (4.31%)
    26 / 510 (5.10%)
         occurrences all number
    24
    43
    Nervous system disorders
    Dysgeusia
         subjects affected / exposed
    59 / 510 (11.57%)
    44 / 510 (8.63%)
         occurrences all number
    74
    56
    Headache
         subjects affected / exposed
    29 / 510 (5.69%)
    26 / 510 (5.10%)
         occurrences all number
    32
    29
    Neuropathy peripheral
         subjects affected / exposed
    76 / 510 (14.90%)
    75 / 510 (14.71%)
         occurrences all number
    81
    80
    Peripheral sensory neuropathy
         subjects affected / exposed
    38 / 510 (7.45%)
    42 / 510 (8.24%)
         occurrences all number
    39
    43
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    157 / 510 (30.78%)
    165 / 510 (32.35%)
         occurrences all number
    209
    207
    Neutropenia
         subjects affected / exposed
    40 / 510 (7.84%)
    58 / 510 (11.37%)
         occurrences all number
    51
    90
    Eye disorders
    Lacrimation increased
         subjects affected / exposed
    16 / 510 (3.14%)
    28 / 510 (5.49%)
         occurrences all number
    17
    28
    Gastrointestinal disorders
    Vomiting
         subjects affected / exposed
    60 / 510 (11.76%)
    59 / 510 (11.57%)
         occurrences all number
    66
    73
    Stomatitis
         subjects affected / exposed
    34 / 510 (6.67%)
    20 / 510 (3.92%)
         occurrences all number
    44
    26
    Nausea
         subjects affected / exposed
    108 / 510 (21.18%)
    134 / 510 (26.27%)
         occurrences all number
    145
    182
    Diarrhoea
         subjects affected / exposed
    175 / 510 (34.31%)
    162 / 510 (31.76%)
         occurrences all number
    294
    244
    Constipation
         subjects affected / exposed
    112 / 510 (21.96%)
    101 / 510 (19.80%)
         occurrences all number
    133
    132
    Skin and subcutaneous tissue disorders
    Nail disorder
         subjects affected / exposed
    37 / 510 (7.25%)
    41 / 510 (8.04%)
         occurrences all number
    38
    42
    Alopecia
         subjects affected / exposed
    172 / 510 (33.73%)
    178 / 510 (34.90%)
         occurrences all number
    172
    178
    Pruritus
         subjects affected / exposed
    48 / 510 (9.41%)
    22 / 510 (4.31%)
         occurrences all number
    55
    27
    Rash
         subjects affected / exposed
    52 / 510 (10.20%)
    36 / 510 (7.06%)
         occurrences all number
    67
    38
    Renal and urinary disorders
    Haematuria
         subjects affected / exposed
    29 / 510 (5.69%)
    22 / 510 (4.31%)
         occurrences all number
    34
    23
    Endocrine disorders
    Hypothyroidism
         subjects affected / exposed
    29 / 510 (5.69%)
    14 / 510 (2.75%)
         occurrences all number
    33
    15
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    84 / 510 (16.47%)
    97 / 510 (19.02%)
         occurrences all number
    103
    108
    Back pain
         subjects affected / exposed
    78 / 510 (15.29%)
    85 / 510 (16.67%)
         occurrences all number
    80
    92
    Bone pain
         subjects affected / exposed
    49 / 510 (9.61%)
    42 / 510 (8.24%)
         occurrences all number
    52
    47
    Myalgia
         subjects affected / exposed
    39 / 510 (7.65%)
    51 / 510 (10.00%)
         occurrences all number
    42
    65
    Pain in extremity
         subjects affected / exposed
    41 / 510 (8.04%)
    52 / 510 (10.20%)
         occurrences all number
    46
    61
    Infections and infestations
    Urinary tract infection
         subjects affected / exposed
    37 / 510 (7.25%)
    31 / 510 (6.08%)
         occurrences all number
    61
    48
    COVID-19
         subjects affected / exposed
    63 / 510 (12.35%)
    62 / 510 (12.16%)
         occurrences all number
    66
    63
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    96 / 510 (18.82%)
    97 / 510 (19.02%)
         occurrences all number
    119
    116
    Hyperglycaemia
         subjects affected / exposed
    34 / 510 (6.67%)
    43 / 510 (8.43%)
         occurrences all number
    37
    52
    Hypocalcaemia
         subjects affected / exposed
    23 / 510 (4.51%)
    29 / 510 (5.69%)
         occurrences all number
    28
    36

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    17 May 2021
    Removed exclusion criterion for prior radium-223 exposure. Aligned dose modification criteria and immuno-oncology (IO) agent management algorithms with National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5. Added serologic testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) status. Incorporated additional updates in order to improve alignment between protocol sections and clarify remote monitoring, prior malignancy window, thyroid testing, and male contraception requirements.
    13 Sep 2022
    Changes to the statistical analysis section, in which the population for radiographic progression-free survival (rPFS) analysis has been changed from the first 544 participants randomized to all randomized and the number of events from 433 to 530 rPFS events. Changes to clarify censoring rules for rPFS. Increased overall survival (OS) events from 615 to 690. Clarification of pharmacokinetic sampling at follow-up visits. Clarification of SARS-CoV-2 serology at follow-up as optional.
    22 Sep 2023
    The purpose of this protocol amendment is to formally incorporate guidance provided in the “Dear Investigator” letters from 27-Jul-2023 and 10-Aug-2023, and further clarify participant management and study procedures as the study proceeds toward termination due to one of the primary efficacy endpoints not meeting the success criterion and the implausibility of success of the other primary endpoint. The decision to terminate the study was not based on any safety concerns or issues. On 26-Jul-2023 the study independent Data Monitoring Committee convened. Based on a clinical data cutoff of 01-Jun-2023, the addition of nivolumab to docetaxel plus prednisone did not result in a statistically significant improvement in radiographic progression-free survival (rPFS) (hazard ratio 0.96; 99% confidence interval [CI] 0.77, 1.19) at final analysis and overall survival (OS) at the first interim analysis (hazard ratio 1.09; 99.41% CI 0.84, 1.43) compared to placebo added to docetaxel plus prednisone. A Sponsor Executive Oversight Committee (EOC) requested to be unblinded to the study results. Further evaluation of OS results showed no plausible scenario of reaching OS statistical significance at subsequent, planned statistical analyses, including the second interim analysis and final analysis. Given the lack of clinical benefit from nivolumab added to docetaxel plus prednisone for the dual primary efficacy endpoints of rPFS and OS, the Sponsor EOC decided to terminate the study. Unblinding of study treatment assignment to full study teams and investigators occurred on 03-Aug-2023.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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