Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43871   clinical trials with a EudraCT protocol, of which   7290   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of Enzalutamide in Subjects with Advanced Hepatocellular Carcinoma

    Summary
    EudraCT number
    		 2014-004283-37
    Trial protocol
    		 GB   ES   IT  
    Global end of trial date
    09 Feb 2021

    Results information
    Results version number
    		 v1(current)
    This version publication date
    28 Jan 2022
    First version publication date
    28 Jan 2022
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    9785-CL-3021
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02528643
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Astellas Pharma Global Development, Inc.
    Sponsor organisation address
    1 Astellas Way, Northbrook, IL, United States, 60062
    Public contact
    Clinical Trial Disclosure, Astellas Pharma Global Development, Inc., astellas.resultsdisclosure@astellas.com
    Scientific contact
    Clinical Trial Disclosure, Astellas Pharma Global Development, Inc., astellas.resultsdisclosure@astellas.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
    09 Feb 2021
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    09 Feb 2021
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of this study was to evaluate the efficacy of enzalutamide in participants with advanced HCC, as measured by overall survival (OS).
    Protection of trial subjects
    This clinical study was written, conducted and reported in accordance with the protocol, International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Good Clinical Practice (GCP) Guidelines, and applicable local regulations, including the European Directive 2001/20/EC, on the protection of human rights, and with the ethical principles that have their origin in the Declaration of Helsinki. Astellas ensures that the use and disclosure of protected health information (PHI) obtained during a research study complies with the federal, national and/or regional legislation related to the privacy and protection of personal information.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    09 Nov 2015
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Efficacy
    Long term follow-up duration
    		 2 Years
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Canada: 5
    Country: Number of subjects enrolled
    Hong Kong: 3
    Country: Number of subjects enrolled
    Italy: 47
    Country: Number of subjects enrolled
    Korea, Republic of: 59
    Country: Number of subjects enrolled
    Puerto Rico: 2
    Country: Number of subjects enrolled
    Spain: 6
    Country: Number of subjects enrolled
    Taiwan: 10
    Country: Number of subjects enrolled
    United Kingdom: 19
    Country: Number of subjects enrolled
    United States: 14
    Worldwide total number of subjects
    165
    EEA total number of subjects
    53
    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)
    87
    From 65 to 84 years
    76
    85 years and over
    2

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Participants were enrolled from 37 sites in 9 countries in Europe, Asia, and North America. Participants with hepatocellular carcinoma (HCC) of any etiology whose disease had progressed on or who were intolerant to sorafenib or other antivascular endothelial growth factor (VEGF) therapy in the advanced setting were enrolled.

    Pre-assignment
    Screening details
    		 Eligible participants were stratified by geographic region (Asia vs other) and Eastern Cooperative Oncology Group (ECOG) performance (0 vs 1) and randomized in a 2:1 ratio. Participants who discontinued treatment entered a follow-up period. Double blind treatment (DB) Open Label (OL)

    Period 1
    Period 1 title
    DB (Median duration up to 14.65 months)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator

    Arms
    Are arms mutually exclusive
    No

    Arm title
    		 Placebo
    Arm description
    		 Participants received enzalutamide matching placebo orally, once daily (QD) during double blind treatment period until disease progression, unacceptable toxicity, or any other discontinuation criterion was met. Median treatment duration was 64 days.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received enzalutamide matching placebo, orally once daily (QD) until disease progression, unacceptable toxicity, or any other discontinuation criterion was met.

    Arm title
    		 Enzalutamide 160 mg
    Arm description
    		 Participants received enzalutamide 160 milligrams (mg) capsules, orally QD during double blind treatment period until disease progression, unacceptable toxicity, or any other discontinuation criterion was met. Eligible participants received enzalutamide 160 mg capsules, orally QD during open label period until disease progression, unacceptable toxicity, or any other discontinuation criterion was met. Median treatment duration was 64 days.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Enzalutamide
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received enzalutamide 160 milligrams (mg) capsules, orally QD during double blind treatment period until disease progression, unacceptable toxicity, or any other discontinuation criterion was met.

    Number of subjects in period 1
    		Placebo Enzalutamide 160 mg
    Started
    55
    110
    Treated
    55
    107
    Completed
    0
    0
    Not completed
    55
    110
         Adverse event, serious fatal
    1
    6
         Consent withdrawn by subject
    2
    8
         Adverse event, non-fatal
    5
    8
         Progressive Disease
    44
    82
         Miscellaneous
    3
    5
         Lost to follow-up
    -
    1
    Period 2
    Period 2 title
    OL (Median duration up to 27.56 months)
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Arm title
    		 Enzalutamide 160 mg
    Arm description
    		 Participants received enzalutamide 160 milligrams (mg) capsules, orally QD during double blind treatment period until disease progression, unacceptable toxicity, or any other discontinuation criterion was met. Eligible participants received enzalutamide 160 mg capsules, orally QD during open label period until disease progression, unacceptable toxicity, or any other discontinuation criterion was met. Median treatment duration was 64 days.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Enzalutamide
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received enzalutamide 160 milligrams (mg) capsules, orally QD during double blind treatment period until disease progression, unacceptable toxicity, or any other discontinuation criterion was met.

    Number of subjects in period 2
    		Enzalutamide 160 mg
    Started
    1
    Completed
    0
    Not completed
    1
         Progressive Disease
    1

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Participants received enzalutamide matching placebo orally, once daily (QD) during double blind treatment period until disease progression, unacceptable toxicity, or any other discontinuation criterion was met. Median treatment duration was 64 days.

    Reporting group title
    Enzalutamide 160 mg
    Reporting group description
    		 Participants received enzalutamide 160 milligrams (mg) capsules, orally QD during double blind treatment period until disease progression, unacceptable toxicity, or any other discontinuation criterion was met. Eligible participants received enzalutamide 160 mg capsules, orally QD during open label period until disease progression, unacceptable toxicity, or any other discontinuation criterion was met. Median treatment duration was 64 days.

    Reporting group values
    		 Placebo Enzalutamide 160 mg Total
    Number of subjects
    		 55 110
    Age categorical
    Units: Subjects
    Age
    Units: years
        arithmetic mean (standard deviation)
    		 62.6 ± 12.5 63.7 ± 10.9 -
    Sex
    Units: Subjects
        Female
    		 6 15 21
        Male
    		 49 95 144
    Race
    Units: Subjects
        White
    		 26 52 78
        Black or African American
    		 3 5 8
        Asian
    		 25 52 77
        Native Hawaiian or Other Pacific Islander
    		 0 1 1
        Other
    		 1 0 1
    Ethnicity
    Units: Subjects
        HISPANIC OR LATINO
    		 0 3 3
        NOT HISPANIC OR LATINO
    		 55 107 162
        UNKNOWN
    		 0 0 0
    Geographic Region
    Units: Subjects
        Asia
    		 24 48 72
        Other
    		 31 62 93
    Eastern Cooperative Oncology Group (ECOG) PS (0, 1)
    ECOG PS was measured on 6 point scale 0-Fully active, able to carry on all pre-disease performance without restriction 1- Restricted in physically strenuous activity but ambulatory & able to carry out work of a light or sedentary nature 2-Ambulatory & capable of all self-care but unable to carry out any work activities Up & about more than 50% of waking hours 3-Capable of only limited self-care, confined to bed or chair more than 50% of waking hours 4-Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair 5-Dead Participants were categorized based on ECOGPS 0 or 1
    Units: Subjects
        ECOG PS = 0
    		 23 43 66
        ECOG PS = 1
    		 32 67 99

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Participants received enzalutamide matching placebo orally, once daily (QD) during double blind treatment period until disease progression, unacceptable toxicity, or any other discontinuation criterion was met. Median treatment duration was 64 days.

    Reporting group title
    Enzalutamide 160 mg
    Reporting group description
    		 Participants received enzalutamide 160 milligrams (mg) capsules, orally QD during double blind treatment period until disease progression, unacceptable toxicity, or any other discontinuation criterion was met. Eligible participants received enzalutamide 160 mg capsules, orally QD during open label period until disease progression, unacceptable toxicity, or any other discontinuation criterion was met. Median treatment duration was 64 days.
    Reporting group title
    Enzalutamide 160 mg
    Reporting group description
    		 Participants received enzalutamide 160 milligrams (mg) capsules, orally QD during double blind treatment period until disease progression, unacceptable toxicity, or any other discontinuation criterion was met. Eligible participants received enzalutamide 160 mg capsules, orally QD during open label period until disease progression, unacceptable toxicity, or any other discontinuation criterion was met. Median treatment duration was 64 days.

    Primary: Overall Survival (OS)

    		 Close Top of page
    End point title
    		 Overall Survival (OS)
    End point description
    OS was defined as the time from the date of randomization until the documented date of death from any cause. Participants who were still alive at the time of the data cut-off date was censored on the last date known to be alive or at the data cutoff date, whichever occurs first. Results based on Kaplan-Meier estimates. Analysis Population Description (APD): The analysis population was the FAS.
    End point type
    Primary
    End point timeframe
    From date of randomization up to data cut-off date 02 Oct 2017 (approximately 22 months); median follow-up time was 14.65 months for enzalutamide and 13.83 for placebo.
    End point values
    		 Placebo Enzalutamide 160 mg
    Number of subjects analysed
    55
    110
    Units: months
        median (confidence interval 95%)
    7.69 (5.82 to 13.77)
    7.75 (6.05 to 9.92)
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Stratified Analysis. The null hypothesis was stated as: OS distributions of the 2 arms are equivalent. The alternative hypothesis was stated as: OS is prolonged in enzalutamide arm. The null hypothesis was tested using a stratified one-sided log-rank test at the 0.10 level. Stratification factors were ECOG performance status and region from eCRF.
    Comparison groups
    Placebo v Enzalutamide 160 mg
    Number of subjects included in analysis
    165
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.248 [1]
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.146
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.774
         upper limit
    		 1.696
    Notes
    [1] - One-sided p-value.
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    Unstratified Analysis. The null hypothesis was stated as: OS distributions of the 2 arms are equivalent. The alternative hypothesis was stated as: OS is prolonged in enzalutamide arm. The null hypothesis was tested using a one-sided log-rank test at the 0.10 level.
    Comparison groups
    Placebo v Enzalutamide 160 mg
    Number of subjects included in analysis
    165
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.252 [2]
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.142
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.773
         upper limit
    		 1.688
    Notes
    [2] - One-sided p-value.

    Secondary: Number of Participants with Adverse Events (AEs)

    		 Close Top of page
    End point title
    		 Number of Participants with Adverse Events (AEs)
    End point description
    Safety was assessed by AEs, which included abnormalities identified during a medical test (laboratory tests, vital signs, ECG) if the abnormality induced clinical signs or symptoms, needed active intervention, interruption or discontinuation of study drug or was clinically significant. A treatment-emergent AE (TEAE) was defined as an AE observed after starting administration of the study drug up to 30 days after last dose of study drug or initiation of new treatment, whichever comes first. AEs were considered as serious if resulted in in death, was life-threatening resulted in persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions, resulted in congenital anomaly or birth defect, required inpatient hospitalization or led to prolongation of hospitalization & other medically important events. APD: Safety analysis set (SAF), which consisted of all participants who have received at least 1 or partial capsule of study drug.
    End point type
    Secondary
    End point timeframe
    From first dose of study drug up to 30days after last dose of study drug median (minimum, maximum) treatment duration was 64.0 (6, 1736) days for enzalutamide and 64.0 (12, 490) for placebo
    End point values
    		 Placebo Enzalutamide 160 mg
    Number of subjects analysed
    55
    107
    Units: Participants
        TEAE
    50
    105
        Drug-related TEAEs
    24
    69
        Deaths
    45
    82
        TEAE Leading to Death
    6
    12
        Drug-related TEAEs Leading to Death
    0
    0
        Serious TEAEs
    22
    47
        Drug-related Serious TEAEs
    3
    7
        TEAEs Leading to Treatment Withdrawal
    14
    34
        Drug-related TEAEs Leading to Treatment Withdrawal
    4
    7
    No statistical analyses for this end point

    Secondary: Plasma Trough Concentrations of Enzalutamide

    		 Close Top of page
    End point title
    		 Plasma Trough Concentrations of Enzalutamide [3]
    End point description
    Blood samples were collected for analysis. APD: The analysis population was the pharmacokinetics analysis set (PKAS), consisted of the subset of the SAF population for whom at least 1 quantifiable enzalutamide and N-desmethyl enzalutamide concentration value was available. Participants who had available concentration data were included in the analysis.
    End point type
    Secondary
    End point timeframe
    Predose at weeks 5, 9 and 13
    Notes
    [3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: PK parameters were analyzed only in the arms where study drug was administered.
    End point values
    		 Enzalutamide 160 mg
    Number of subjects analysed
    96
    Units: μg/mL
    arithmetic mean (standard deviation)
        Week 5
    14.29 ± 4.15
        Week 9
    12.15 ± 4.68
        Week 13
    12.45 ± 5.44
    No statistical analyses for this end point

    Secondary: Plasma Trough Concentrations N-desmethyl Enzalutamide (M2 Metabolite)

    		 Close Top of page
    End point title
    		 Plasma Trough Concentrations N-desmethyl Enzalutamide (M2 Metabolite) [4]
    End point description
    Blood samples were collected for analysis. APD: The analysis population was the PKAS, with participants who had available concentration data.
    End point type
    Secondary
    End point timeframe
    Predose at weeks 5, 9 and 13
    Notes
    [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: PK parameters were analyzed only in the arms where study drug was administered.
    End point values
    		 Enzalutamide 160 mg
    Number of subjects analysed
    96
    Units: μg/mL
    arithmetic mean (standard deviation)
        Week 5
    11.01 ± 3.63
        Week 9
    12.65 ± 3.89
        Week 13
    12.21 ± 4.94
    No statistical analyses for this end point

    Secondary: Plasma Trough Concentrations of MDPC0001 (M1 Metabolite)

    		 Close Top of page
    End point title
    		 Plasma Trough Concentrations of MDPC0001 (M1 Metabolite) [5]
    End point description
    Blood samples were collected for analysis. APD: The analysis population was the PKAS, with participants who had available concentration data.
    End point type
    Secondary
    End point timeframe
    Predose at weeks 5, 9 and 13
    Notes
    [5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: PK parameters were analyzed only in the arms where study drug was administered.
    End point values
    		 Enzalutamide 160 mg
    Number of subjects analysed
    96
    Units: μg/mL
    arithmetic mean (standard deviation)
        Week 5
    4.70 ± 3.86
        Week 9
    5.60 ± 5.63
        Week 13
    6.12 ± 4.24
    No statistical analyses for this end point

    Secondary: Progression Free Survival (PFS)

    		 Close Top of page
    End point title
    		 Progression Free Survival (PFS)
    End point description
    PFS was defined as the time from date of randomization until date of documented radiographic disease progression according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as determined by investigator or death from any cause on study, whichever occurred first. The earliest of censoring times was used: Participants with (1) no evaluable postbaseline imaging assessments or did not die were censored at randomization date; (2) no radiographical progression or did not die before analysis cutoff date were censored at last radiological assessment date before analysis cutoff date; (3) with no radiographical progression or did not die before new HCC treatment was censored at the last radiological assessment date before start of new HCC treatment. Based on Kaplan-Meier. APD: FAS population.
    End point type
    Secondary
    End point timeframe
    From date of randomization up to data cut-off date 02 Oct 2017 (approximately 22 months); median follow-up time was 14.65 months for enzalutamide and 13.83 for placebo.
    End point values
    		 Placebo Enzalutamide 160 mg
    Number of subjects analysed
    55
    110
    Units: months
        median (confidence interval 95%)
    1.87 (1.84 to 3.45)
    2.23 (1.87 to 3.52)
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    Unstratified Analysis. The null hypothesis was stated as: PFS distributions of the 2 arms are equivalent. The alternative hypothesis was stated as: PFS is prolonged in enzalutamide arm. The null hypothesis was tested using a one-sided log-rank test at the 0.10 level.
    Comparison groups
    Placebo v Enzalutamide 160 mg
    Number of subjects included in analysis
    165
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.586 [6]
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.959
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.684
         upper limit
    		 1.345
    Notes
    [6] - One-sided p-value.
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Stratified Analysis. The null hypothesis was stated as: PFS distributions of the 2 arms are equivalent. The alternative hypothesis was stated as: PFS is prolonged in enzalutamide arm. The null hypothesis was tested using a stratified one-sided log-rank test at the 0.10 level. Stratification factors were ECOG performance status and region from eCRF.
    Comparison groups
    Placebo v Enzalutamide 160 mg
    Number of subjects included in analysis
    165
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.396 [7]
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.039
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.732
         upper limit
    		 1.474
    Notes
    [7] - One-sided p-value.

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    From first dose of study drug up to 30days after last dose of study drug median (minimum, maximum) treatment duration was 64.0 (6, 1736) days for enzalutamide and 64.0 (12, 490) for placebo
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    v16.1
    Reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Participants received enzalutamide matching placebo orally, QD during double blind treatment period until disease progression, unacceptable toxicity, or any other discontinuation criterion was met. Median treatment duration was 64 days.

    Reporting group title
    Enzalutamide
    Reporting group description
    		 Participants received enzalutamide 160 mg capsules, orally, QD during double blind treatment period until disease progression, unacceptable toxicity, or any other discontinuation criterion was met. Eligible participants received enzalutamide 160 mg capsules, orally QD during open label period until disease progression, unacceptable toxicity, or any other discontinuation criterion was met. Median treatment duration was 64 days.

    Serious adverse events
    		 Placebo Enzalutamide
    Total subjects affected by serious adverse events
         subjects affected / exposed
    22 / 55 (40.00%)
    47 / 107 (43.93%)
         number of deaths (all causes)
    45
    82
         number of deaths resulting from adverse events
    6
    12
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Gastric cancer
         subjects affected / exposed
    1 / 55 (1.82%)
    0 / 107 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metastases to central nervous system
         subjects affected / exposed
    0 / 55 (0.00%)
    1 / 107 (0.93%)
         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
    6 / 55 (10.91%)
    14 / 107 (13.08%)
         occurrences causally related to treatment / all
    1 / 7
    0 / 20
         deaths causally related to treatment / all
    0 / 5
    0 / 11
    Tumour pain
         subjects affected / exposed
    1 / 55 (1.82%)
    0 / 107 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tumour haemorrhage
         subjects affected / exposed
    2 / 55 (3.64%)
    1 / 107 (0.93%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    0 / 55 (0.00%)
    3 / 107 (2.80%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chest pain
         subjects affected / exposed
    0 / 55 (0.00%)
    1 / 107 (0.93%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Facial pain
         subjects affected / exposed
    1 / 55 (1.82%)
    0 / 107 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pain
         subjects affected / exposed
    0 / 55 (0.00%)
    1 / 107 (0.93%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oedema peripheral
         subjects affected / exposed
    0 / 55 (0.00%)
    2 / 107 (1.87%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General physical health deterioration
         subjects affected / exposed
    0 / 55 (0.00%)
    2 / 107 (1.87%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Pyrexia
         subjects affected / exposed
    0 / 55 (0.00%)
    1 / 107 (0.93%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Pelvic pain
         subjects affected / exposed
    1 / 55 (1.82%)
    0 / 107 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    0 / 55 (0.00%)
    1 / 107 (0.93%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    1 / 55 (1.82%)
    1 / 107 (0.93%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Epistaxis
         subjects affected / exposed
    0 / 55 (0.00%)
    1 / 107 (0.93%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    1 / 55 (1.82%)
    0 / 107 (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
    0 / 55 (0.00%)
    1 / 107 (0.93%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Mental status changes
         subjects affected / exposed
    0 / 55 (0.00%)
    1 / 107 (0.93%)
         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
    0 / 55 (0.00%)
    1 / 107 (0.93%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 55 (0.00%)
    1 / 107 (0.93%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood bilirubin increased
         subjects affected / exposed
    0 / 55 (0.00%)
    2 / 107 (1.87%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood creatinine increased
         subjects affected / exposed
    0 / 55 (0.00%)
    1 / 107 (0.93%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Atrial fibrillation
         subjects affected / exposed
    1 / 55 (1.82%)
    0 / 107 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrioventricular block complete
         subjects affected / exposed
    1 / 55 (1.82%)
    0 / 107 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Dysaesthesia
         subjects affected / exposed
    1 / 55 (1.82%)
    0 / 107 (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
    0 / 55 (0.00%)
    2 / 107 (1.87%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal cord compression
         subjects affected / exposed
    0 / 55 (0.00%)
    1 / 107 (0.93%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 55 (1.82%)
    3 / 107 (2.80%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lymph node pain
         subjects affected / exposed
    0 / 55 (0.00%)
    1 / 107 (0.93%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    0 / 55 (0.00%)
    1 / 107 (0.93%)
         occurrences causally related to treatment / all
    0 / 0
    8 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eye disorders
    Conjunctivitis
         subjects affected / exposed
    0 / 55 (0.00%)
    1 / 107 (0.93%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal distension
         subjects affected / exposed
    0 / 55 (0.00%)
    2 / 107 (1.87%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal pain
         subjects affected / exposed
    1 / 55 (1.82%)
    7 / 107 (6.54%)
         occurrences causally related to treatment / all
    0 / 1
    2 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal pain upper
         subjects affected / exposed
    0 / 55 (0.00%)
    1 / 107 (0.93%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ascites
         subjects affected / exposed
    0 / 55 (0.00%)
    5 / 107 (4.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    0 / 55 (0.00%)
    1 / 107 (0.93%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    1 / 55 (1.82%)
    0 / 107 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematemesis
         subjects affected / exposed
    1 / 55 (1.82%)
    0 / 107 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Duodenitis
         subjects affected / exposed
    1 / 55 (1.82%)
    0 / 107 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 55 (0.00%)
    1 / 107 (0.93%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    0 / 55 (0.00%)
    1 / 107 (0.93%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oesophageal varices haemorrhage
         subjects affected / exposed
    0 / 55 (0.00%)
    1 / 107 (0.93%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oesophagitis
         subjects affected / exposed
    1 / 55 (1.82%)
    0 / 107 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 55 (0.00%)
    2 / 107 (1.87%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    0 / 55 (0.00%)
    2 / 107 (1.87%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Hepatic failure
         subjects affected / exposed
    0 / 55 (0.00%)
    1 / 107 (0.93%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute hepatic failure
         subjects affected / exposed
    1 / 55 (1.82%)
    0 / 107 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic function abnormal
         subjects affected / exposed
    0 / 55 (0.00%)
    1 / 107 (0.93%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Hydronephrosis
         subjects affected / exposed
    0 / 55 (0.00%)
    1 / 107 (0.93%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal failure acute
         subjects affected / exposed
    2 / 55 (3.64%)
    3 / 107 (2.80%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    1 / 55 (1.82%)
    3 / 107 (2.80%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bone pain
         subjects affected / exposed
    0 / 55 (0.00%)
    1 / 107 (0.93%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Muscular weakness
         subjects affected / exposed
    1 / 55 (1.82%)
    2 / 107 (1.87%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pain in extremity
         subjects affected / exposed
    1 / 55 (1.82%)
    1 / 107 (0.93%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    1 / 55 (1.82%)
    0 / 107 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchopneumonia
         subjects affected / exposed
    1 / 55 (1.82%)
    0 / 107 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Clostridium difficile colitis
         subjects affected / exposed
    0 / 55 (0.00%)
    1 / 107 (0.93%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatitis B
         subjects affected / exposed
    1 / 55 (1.82%)
    0 / 107 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower respiratory tract infection
         subjects affected / exposed
    0 / 55 (0.00%)
    1 / 107 (0.93%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    1 / 55 (1.82%)
    0 / 107 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    1 / 55 (1.82%)
    0 / 107 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    0 / 55 (0.00%)
    1 / 107 (0.93%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dehydration
         subjects affected / exposed
    1 / 55 (1.82%)
    0 / 107 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fluid intake reduced
         subjects affected / exposed
    0 / 55 (0.00%)
    1 / 107 (0.93%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperkalaemia
         subjects affected / exposed
    0 / 55 (0.00%)
    1 / 107 (0.93%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolic acidosis
         subjects affected / exposed
    0 / 55 (0.00%)
    1 / 107 (0.93%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Placebo Enzalutamide
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    46 / 55 (83.64%)
    96 / 107 (89.72%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    0 / 55 (0.00%)
    6 / 107 (5.61%)
         occurrences all number
    0
    14
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    11 / 55 (20.00%)
    11 / 107 (10.28%)
         occurrences all number
    12
    26
    Fatigue
         subjects affected / exposed
    10 / 55 (18.18%)
    38 / 107 (35.51%)
         occurrences all number
    11
    49
    Oedema peripheral
         subjects affected / exposed
    3 / 55 (5.45%)
    6 / 107 (5.61%)
         occurrences all number
    3
    7
    Pyrexia
         subjects affected / exposed
    5 / 55 (9.09%)
    8 / 107 (7.48%)
         occurrences all number
    5
    9
    Reproductive system and breast disorders
    Gynaecomastia
         subjects affected / exposed
    0 / 55 (0.00%)
    12 / 107 (11.21%)
         occurrences all number
    0
    14
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    6 / 55 (10.91%)
    8 / 107 (7.48%)
         occurrences all number
    6
    11
    Cough
         subjects affected / exposed
    6 / 55 (10.91%)
    12 / 107 (11.21%)
         occurrences all number
    6
    14
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    7 / 55 (12.73%)
    13 / 107 (12.15%)
         occurrences all number
    7
    14
    Investigations
    Aspartate aminotransferase increased
         subjects affected / exposed
    9 / 55 (16.36%)
    16 / 107 (14.95%)
         occurrences all number
    10
    23
    Alanine aminotransferase increased
         subjects affected / exposed
    7 / 55 (12.73%)
    8 / 107 (7.48%)
         occurrences all number
    10
    8
    Blood alkaline phosphatase increased
         subjects affected / exposed
    4 / 55 (7.27%)
    5 / 107 (4.67%)
         occurrences all number
    4
    5
    Blood bilirubin increased
         subjects affected / exposed
    2 / 55 (3.64%)
    6 / 107 (5.61%)
         occurrences all number
    2
    9
    Weight decreased
         subjects affected / exposed
    5 / 55 (9.09%)
    15 / 107 (14.02%)
         occurrences all number
    6
    17
    Cardiac disorders
    Tachycardia
         subjects affected / exposed
    3 / 55 (5.45%)
    0 / 107 (0.00%)
         occurrences all number
    3
    0
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    5 / 55 (9.09%)
    4 / 107 (3.74%)
         occurrences all number
    7
    7
    Headache
         subjects affected / exposed
    4 / 55 (7.27%)
    7 / 107 (6.54%)
         occurrences all number
    4
    9
    Dysgeusia
         subjects affected / exposed
    4 / 55 (7.27%)
    2 / 107 (1.87%)
         occurrences all number
    5
    2
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    7 / 55 (12.73%)
    12 / 107 (11.21%)
         occurrences all number
    8
    17
    Gastrointestinal disorders
    Abdominal discomfort
         subjects affected / exposed
    3 / 55 (5.45%)
    2 / 107 (1.87%)
         occurrences all number
    3
    2
    Abdominal distension
         subjects affected / exposed
    3 / 55 (5.45%)
    6 / 107 (5.61%)
         occurrences all number
    6
    6
    Abdominal pain
         subjects affected / exposed
    8 / 55 (14.55%)
    15 / 107 (14.02%)
         occurrences all number
    9
    24
    Ascites
         subjects affected / exposed
    2 / 55 (3.64%)
    11 / 107 (10.28%)
         occurrences all number
    2
    16
    Abdominal pain upper
         subjects affected / exposed
    9 / 55 (16.36%)
    7 / 107 (6.54%)
         occurrences all number
    9
    10
    Constipation
         subjects affected / exposed
    5 / 55 (9.09%)
    15 / 107 (14.02%)
         occurrences all number
    5
    18
    Diarrhoea
         subjects affected / exposed
    13 / 55 (23.64%)
    13 / 107 (12.15%)
         occurrences all number
    22
    17
    Dyspepsia
         subjects affected / exposed
    6 / 55 (10.91%)
    9 / 107 (8.41%)
         occurrences all number
    6
    13
    Nausea
         subjects affected / exposed
    6 / 55 (10.91%)
    29 / 107 (27.10%)
         occurrences all number
    6
    33
    Vomiting
         subjects affected / exposed
    5 / 55 (9.09%)
    11 / 107 (10.28%)
         occurrences all number
    5
    13
    Skin and subcutaneous tissue disorders
    Pruritus
         subjects affected / exposed
    4 / 55 (7.27%)
    13 / 107 (12.15%)
         occurrences all number
    4
    14
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    3 / 55 (5.45%)
    4 / 107 (3.74%)
         occurrences all number
    3
    5
    Back pain
         subjects affected / exposed
    3 / 55 (5.45%)
    10 / 107 (9.35%)
         occurrences all number
    3
    13
    Bone pain
         subjects affected / exposed
    3 / 55 (5.45%)
    2 / 107 (1.87%)
         occurrences all number
    3
    2
    Musculoskeletal pain
         subjects affected / exposed
    4 / 55 (7.27%)
    6 / 107 (5.61%)
         occurrences all number
    8
    6
    Pain in extremity
         subjects affected / exposed
    3 / 55 (5.45%)
    3 / 107 (2.80%)
         occurrences all number
    4
    3
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    12 / 55 (21.82%)
    33 / 107 (30.84%)
         occurrences all number
    13
    40
    Hyperkalaemia
         subjects affected / exposed
    5 / 55 (9.09%)
    2 / 107 (1.87%)
         occurrences all number
    5
    3

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    23 Sep 2015
    The changes included ● The TTP endpoint was changed from a secondary endpoint to an exploratory endpoint, because TTP is not an established endpoint in this study population. ● Study procedures related to testing on eligibility tissue samples were updated. ● In order to be consistent with the enzalutamide US label, the concomitant medications were modified to clarify advice regarding coadministration with cytochrome P450 (CYP)2C8 inhibitors and warfarin (CYP2C9 substrate). ● The definition of the full analysis set (FAS) was changed from “all randomized patients who receive at least 1 dose of study drug” to “all randomized patients.”
    29 Mar 2016
    The changes included ● Advanced HCC was clarified as unresectable and/or metastatic and that the additional line of systemic therapy could have been given before or after sorafenib/anti-VEGF therapy. ● The number of unstained serial tissue slides requirement was removed from Inclusion Criterion 10. ● Clarified Exclusion Criterion 8 to state that transfusions/infusions to meet eligibility criteria were not allowed. ● Clarified Exclusion Criterion 10 to state that only bleeding esophageal varices were exclusionary. ● Added dosing information for clarity and completeness and to align with the Enzalutamide IB and US Package Insert. ● Clarified the values and dose modifications for clinically significant study drug-related liver toxicities. ● Added guidance that the investigator should consult with medical monitor if initiation of antiviral therapy was deemed necessary during the study. ● Included a pharmacodynamic analysis set (PDAS) and removed the per-protocol set (PPS). The efficacy analysis would be conducted on the FAS and would not include the PPS. ● Replaced AEs with treatment-emergent AEs (TEAEs). All analyses would be done on TEAEs only.
    10 Aug 2016
    The changes included ● Added language to allow patients previously using spironolactone (an AR signal inhibitor) to be enrolled in the study, and allowed spironolactone to be initiated during the study after consultation with the medical monitor. ● Nonsubstantial change: Updated data cutoff and increased the number of patients to be treated with enzalutamide.
    08 Mar 2018
    The changes included ● Added open-label period to allow patients to continue on enzalutamide after the doubleblind period. ● Nonsubstantial change: Updated clinical research contact details.

    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
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Sun May 05 15:27:07 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA