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 are conducted in the European Union (EU) and the European Economic Area (EEA);
  • clinical trials conducted outside the EU / EEA that are linked to European paediatric-medicine development.
  • Learn   more about the EU Clinical Trials Register   including the source of the information and the legal basis.


    The EU Clinical Trials Register currently displays   36835   clinical trials with a EudraCT protocol, of which   6081   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).
     
    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, Open-Label, Single-Arm, Multidose Study to Investigate the Effects of Orteronel on the QT/QTc Interval in Patients with Metastatic Castration-Resistant Prostate Cancer

    Summary
    EudraCT number
    2012-000136-26
    Trial protocol
    GR   IE   FR  
    Global end of trial date
    21 Jan 2015

    Results information
    Results version number
    v1(current)
    This version publication date
    04 May 2016
    First version publication date
    04 May 2016
    Other versions

    Trial information

    Close Top of page
    Trial identification
    Sponsor protocol code
    C21012
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT01549951
    WHO universal trial number (UTN)
    U1111-1179-5656
    Sponsors
    Sponsor organisation name
    Millennium Pharmaceuticals, Inc.
    Sponsor organisation address
    61 Aldwych, London, United Kingdom, WC2B 4AE
    Public contact
    Study Manager, Millennium Medical and Drug Information Center, 001 866-835-2233, GlobalOncologyMedinfo@takeda.com
    Scientific contact
    Study Manager, Millennium Medical and Drug Information Center, 001 866-835-2233, GlobalOncologyMedinfo@takeda.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
    29 Jun 2015
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    21 Jan 2015
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The purpose of this phase 2, open-label, single-arm, multidose, multicenter study is to investigate the effects of Orteronel plus Prednisone on the QT/QTc interval in patients with Metastatic Castration-Resistant Prostrate Cancer
    Protection of trial subjects
    All study subjects were required to read and sign an Informed Consent Form.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    29 May 2012
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    Safety
    Long term follow-up duration
    3 Years
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    France: 20
    Country: Number of subjects enrolled
    United States: 16
    Country: Number of subjects enrolled
    Canada: 7
    Country: Number of subjects enrolled
    Greece: 4
    Country: Number of subjects enrolled
    Ireland: 2
    Country: Number of subjects enrolled
    Romania: 1
    Worldwide total number of subjects
    50
    EEA total number of subjects
    27
    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)
    18
    From 65 to 84 years
    32
    85 years and over
    0

    Subject disposition

    Close Top of page
    Recruitment
    Recruitment details
    Subjects took part in the study at 16 investigative sites in Canada, France, Greece, Ireland, Romania, and the United States from 29 May 2012 to 21 January 2015.

    Pre-assignment
    Screening details
    Male subjects with a historical diagnosis of metastatic castration-resistant prostate cancer (mCRPC) were enrolled in this single arm study to receive orteronel 400 milligram (mg) along with prednisone 5 mg twice daily for 28 days in each treatment cycle.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    Yes
    Allocation method
    Non-randomised - controlled
    Blinding used
    Not blinded

    Arms
    Arm title
    Orteronel + Prednisone
    Arm description
    Orteronel 400 mg, tablets, orally, twice daily along with prednisone 5 mg, tablets, orally, twice daily for 2 treatment cycles of 28 days each. Gonadotropin-releasing hormone analogue therapy was supplied as a commercially available dosage formulation.
    Arm type
    Experimental

    Investigational medicinal product name
    Orteronel
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Orteronel 400 mg, tablets, orally, twice daily for 2 treatment cycles of 28 days each.

    Investigational medicinal product name
    Prednisone
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Prednisone 5 mg, tablets, orally, twice daily for 2 treatment cycles of 28 days each.

    Number of subjects in period 1
    Orteronel + Prednisone
    Started
    50
    Primary reason off study treatment
    50
    Completed
    0
    Not completed
    50
         Progressive disease
    29
         Unsatisfactory therapeutic response
    1
         Unknown
    2
         Symptomatic deterioration
    1
         Adverse event, non-fatal
    15
         Consent withdrawn by subject
    2

    Baseline characteristics

    Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Orteronel + Prednisone
    Reporting group description
    Orteronel 400 mg, tablets, orally, twice daily along with prednisone 5 mg, tablets, orally, twice daily for 2 treatment cycles of 28 days each. Gonadotropin-releasing hormone analogue therapy was supplied as a commercially available dosage formulation.

    Reporting group values
    Orteronel + Prednisone Total
    Number of subjects
    50 50
    Age categorical
    Units: Subjects
        In utero
    0 0
        Preterm newborn infants (gestational age < 37 wks)
    0 0
        Newborns (0-27 days)
    0 0
        Infants and toddlers (28 days-23 months)
    0 0
        Children (2-11 years)
    0 0
        Adolescents (12-17 years)
    0 0
        Adults (18-64 years)
    18 18
        From 65-84 years
    32 32
        85 years and over
    0 0
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    68.7 ± 8.85 -
    Gender, Male/Female
    Units: subjects
        Female
    0 0
        Male
    50 50
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    1 1
        Not Hispanic or Latino
    27 27
        Unknown or Not Reported
    22 22
    Race/Ethnicity, Customized
    Units: Subjects
        White
    27 27
        Black/African American
    3 3
        Not reported
    20 20
    Eastern Cooperative Oncology Group (ECOG) performance status
    ECOG assessed subject's performance status on 5point scale: 0=Fully active/able to carry on all pre-disease activities without restriction;1=restricted in physically strenuous activity,ambulatory/able to carry out light or sedentary work;2=ambulatory (greater than[>] 50 percent[%] of waking hours),capable of all self care,unable to carry out any work activities;3=capable of only limited selfcare,confined to bed/chair>50% of waking hours;4=completely disabled,cannot carry on any selfcare,totally confined to bed/chair;5=dead. Subject with performance status as 0 and 1 have been reported.
    Units: Subjects
        '0'
    38 38
        '1'
    12 12
    Histological classification
    Carcinoma was classified as adenocarcinoma in situ (local), not otherwise specified (NOS) and adenocarcinoma, NOS.
    Units: Subjects
        Adenocarcinoma in situ, NOS
    8 8
        Adenocarcinoma, NOS
    42 42
    Height
    Units: centimeters (cm)
        arithmetic mean (standard deviation)
    175.32 ± 7.521 -
    Weight
    Units: kilograms (kg)
        arithmetic mean (standard deviation)
    87.63 ± 14.797 -
    Time from initial prostate cancer diagnosis
    Time from initial diagnosis was defined as (first dose date – initial diagnosis date + 1) / 365.25.
    Units: years
        arithmetic mean (standard deviation)
    6.32 ± 5.325 -

    End points

    Close Top of page
    End points reporting groups
    Reporting group title
    Orteronel + Prednisone
    Reporting group description
    Orteronel 400 mg, tablets, orally, twice daily along with prednisone 5 mg, tablets, orally, twice daily for 2 treatment cycles of 28 days each. Gonadotropin-releasing hormone analogue therapy was supplied as a commercially available dosage formulation.

    Primary: Maximum Change From Baseline in QTc Interval Based on the Fridericia Correction (QTcF) Method

    Close Top of page
    End point title
    Maximum Change From Baseline in QTc Interval Based on the Fridericia Correction (QTcF) Method [1]
    End point description
    Triplicate 12-lead electrocardiogram (ECG) measurements (each recording separated by approximately 1 minute) were performed and average was calculated. The time corresponding to beginning of depolarization to repolarization of the ventricles (QT interval) was adjusted for RR interval using QT and RR from each ECG by Fridericia’s formula (QTcF = QT divided by cube root of RR). Results of change in QTcF analyzed from 12-lead ECGs performed at each time point were averaged for analysis and a maximum across all post-dosing time points was used. Baseline is defined as the average of the triplicate 12-lead ECG measurements taken at the specified time prior to dosing. ECG analysis population was defined as all subjects with at least 1 available baseline and at least 1 on-treatment ECG who received at least 1 dose of any study drug.
    End point type
    Primary
    End point timeframe
    Cycle 1 (28 day cycle), Day 1: pre-dose and at multiple timepoints (up to 6 hours) post-dose; Cycle 2 (28 day cycle), Day 1: pre-dose and at multiple timepoints (up to 6 hours) post-dose
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be analyzed for this endpoint.
    End point values
    Orteronel + Prednisone
    Number of subjects analysed
    43
    Units: millisecond (msec)
        arithmetic mean (standard deviation)
    -1.4 ± 19.64
    No statistical analyses for this end point

    Secondary: Maximum Change From Baseline in QTc Based on the Bazett Correction (QTcB) Method, PR, QRS and Uncorrected QT Interval

    Close Top of page
    End point title
    Maximum Change From Baseline in QTc Based on the Bazett Correction (QTcB) Method, PR, QRS and Uncorrected QT Interval
    End point description
    Triplicate 12-lead ECG measurements (each recording separated by approximately 1 minutes) were performed and average was calculated. The time corresponding to beginning of depolarization to repolarization of the ventricles (QT interval) was adjusted for RR interval using QT and RR from each ECG by Bazette’s formula (QTcB = QT divided by square root of RR). Results of change in QTcB, PR, QRS and uncorrected QT analyzed from 12-lead ECGs performed at each time point were averaged for analysis and a maximum across all post-dosing time points was used. Baseline is defined as the average of the triplicate 12-lead ECG measurements taken at the specified time prior to dosing. ECG analysis population was defined as all subjects with at least 1 available baseline and at least 1 on-treatment ECG who received at least 1 dose of any study drug.
    End point type
    Secondary
    End point timeframe
    Cycle 1 (28 day cycle), Day 1: pre-dose and at multiple timepoints (up to 6 hours) post-dose; Cycle 2 (28 day cycle), Day 1: pre-dose and at multiple timepoints (up to 6 hours) post-dose
    End point values
    Orteronel + Prednisone
    Number of subjects analysed
    48
    Units: msec
    arithmetic mean (standard deviation)
        QTcB Interval (N=43)
    9.7 ± 22.61
        PR Interval (N=48)
    -4.2 ± 7.4
        QRS Interval (N=48)
    -1 ± 2.8
        Uncorrected QT Interval (N=48)
    -12.5 ± 17
    No statistical analyses for this end point

    Secondary: Changes From Baseline in Heart Rate

    Close Top of page
    End point title
    Changes From Baseline in Heart Rate
    End point description
    Triplicate 12-lead Electrocardiogram (ECG) measurements were performed and average was calculated. Supine heart rate was measured as beats per minute (bpm). Results of change in heart rate analyzed from 12-lead ECGs performed at each time point were averaged for analysis and a maximum across all post-dosing time points was used. Baseline is defined as the average of the triplicate 12-lead ECG measurements taken at the specified time prior to dosing. ECG analysis population was defined as all subjects with at least 1 available baseline and at least 1 on-treatment ECG who received at least 1 dose of any study drug.
    End point type
    Secondary
    End point timeframe
    Cycle 1 (28 day cycle), Day 1: pre-dose and at multiple timepoints (up to 6 hours) post-dose; Cycle 2 (28 day cycle), Day 1: pre-dose and at multiple timepoints (up to 6 hours) post-dose
    End point values
    Orteronel + Prednisone
    Number of subjects analysed
    48
    Units: bpm
        arithmetic mean (standard deviation)
    5.7 ± 8
    No statistical analyses for this end point

    Secondary: Number of Subjects Reporting Change From Baseline in ECG Morphology

    Close Top of page
    End point title
    Number of Subjects Reporting Change From Baseline in ECG Morphology
    End point description
    Subjects with incidence of ECG morphology abnormalities were observed. Types of abnormalities included appearance of abnormal U waves,T waves inversion,elevation of ST segment,depression of ST segment,second or third degree heart block,right or left bundle branch block,atrial fibrillation/flutter,and myocardial infarction.New morphological changes were observed in abnormal U waves,depression of ST segment,and T waves inversion.Here,'new' refers to change not present at baseline, ie, at any evaluation predose, and only seen postbaseline.Results of change in ECG morphology analyzed from 12-leadECG at each time point were averaged for analysis and a maximum across all post-dosing time points was used.Baseline is defined as the average of the triplicate 12-lead ECG measurements taken at the specified time prior to dosing.ECG analysis population was defined as all subjects with at least 1 available baseline and at least 1 on-treatment ECG who received at least 1 dose of any study drug.
    End point type
    Secondary
    End point timeframe
    Cycle 1 (28 day cycle), Day 1: pre-dose and at multiple timepoints (up to 6 hours) post-dose; Cycle 2 (28 day cycle), Day 1: pre-dose and at multiple timepoints (up to 6 hours) post-dose
    End point values
    Orteronel + Prednisone
    Number of subjects analysed
    48
    Units: subjects
    number (not applicable)
        Abnormal U waves
    1
        ST segment depression
    8
        T-wave inversion
    3
    No statistical analyses for this end point

    Secondary: AUC(0-6): Area Under the Plasma Concentration-Time Curve From Time 0 to 6 Hours Postdose for Orteronel and M-I metabolite

    Close Top of page
    End point title
    AUC(0-6): Area Under the Plasma Concentration-Time Curve From Time 0 to 6 Hours Postdose for Orteronel and M-I metabolite
    End point description
    AUC(0-6) is measure of area under the curve over the dosing interval (tau) (AUC(0-tau]), where tau is the length of the dosing interval - 6 hours in this study). Average results at each time point were analyzed and a maximum across all post-dosing time points was used. Baseline is defined as the average of the triplicate 12-lead ECG measurements taken at the specified time prior to dosing. Pharmacokinetic (PK) population was defined as all subjects who had sufficient dosing data and plasma concentration-time data to permit calculations of PK parameters.
    End point type
    Secondary
    End point timeframe
    Cycle 1 (28 day cycle), Day 1: pre-dose and at multiple timepoints (up to 6 hours) post-dose; Cycle 2 (28 day cycle), Day 1: pre-dose and at multiple timepoints (up to 6 hours) post-dose
    End point values
    Orteronel + Prednisone
    Number of subjects analysed
    50
    Units: nanogram hours per milliliter (ng*hr/mL)
    arithmetic mean (standard deviation)
        Cycle 1 Day 1 (n=50)
    7570.4 ± 3673.31
        Cycle 2 Day 1 (n=44)
    12971.6 ± 6071.18
    No statistical analyses for this end point

    Secondary: Correlation Between the QTcF Change From Baseline and Plasma Concentrations of Orteronel

    Close Top of page
    End point title
    Correlation Between the QTcF Change From Baseline and Plasma Concentrations of Orteronel
    End point description
    Coefficient of correlation was measured using linear mixed effects model for the association between two variables; change from baseline versus the plasma concentration. Subjects’s effects on the intercept and plasma concentration slope were included in the model as random effects terms. Plasma concentrations were re scaled for model convergence. Average results at each time point were analyzed and a maximum across all post-dosing time points was used. Baseline is defined as the average of the triplicate 12-lead ECG measurements taken at the specified time prior to dosing. ECG analysis population was defined as all subjects with at least 1 available baseline and at least 1 on-treatment ECG who received at least 1 dose of any study drug.
    End point type
    Secondary
    End point timeframe
    Cycle 1 (28 day cycle), Day 1: pre-dose and at multiple timepoints (up to 6 hours) post-dose; Cycle 2 (28 day cycle), Day 1: pre-dose and at multiple timepoints (up to 6 hours) post-dose
    End point values
    Orteronel + Prednisone
    Number of subjects analysed
    48
    Units: correlation coefficient
        least squares mean (standard error)
    -0.002603 ± 0.001053
    No statistical analyses for this end point

    Secondary: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Orteronel and M-I metabolite

    Close Top of page
    End point title
    Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Orteronel and M-I metabolite
    End point description
    Tmax: Time to reach the maximum plasma concentration (Cmax), equal to time (hours) to Cmax. Average results at each time point were analyzed and a maximum across all post-dosing time points was used. Baseline is defined as the average of the triplicate 12-lead ECG measurements taken at the specified time prior to dosing. PK population was defined as all subjects who had sufficient dosing data and plasma concentration-time data to permit calculations of PK parameters.
    End point type
    Secondary
    End point timeframe
    Cycle 1 (28 day cycle), Day 1: pre-dose and at multiple timepoints (up to 6 hours) post-dose; Cycle 2 (28 day cycle), Day 1: pre-dose and at multiple timepoints (up to 6 hours) post-dose
    End point values
    Orteronel + Prednisone
    Number of subjects analysed
    50
    Units: hours
    median (full range (min-max))
        Orteronel: Cycle 1 Day 1 (n=50)
    2 (1 to 5)
        Orteronel: Cycle 2 Day 1 (n=44)
    1.6 (0.5 to 6)
        M-I metabolite: Cycle 1 Day 1 (n=50)
    4.5 (1.5 to 6.2)
        M-I metabolite: Cycle 2 Day 1 (n=44)
    3 (0 to 6.1)
    No statistical analyses for this end point

    Secondary: Cmax: Maximum Observed Plasma Concentration for Orteronel and M-I metabolite

    Close Top of page
    End point title
    Cmax: Maximum Observed Plasma Concentration for Orteronel and M-I metabolite
    End point description
    Maximum observed plasma concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve. Average results at each time point were analyzed and a maximum across all post-dosing time points was used. Baseline is defined as the average of the triplicate 12-lead ECG measurements taken at the specified time prior to dosing. PK population was defined as all subjects who had sufficient dosing data and plasma concentration-time data to permit calculations of PK parameters. 
    End point type
    Secondary
    End point timeframe
    Cycle 1 (28 day cycle), Day 1: pre-dose and at multiple timepoints (up to 6 hours) post-dose; Cycle 2 (28 day cycle), Day 1: pre-dose and at multiple timepoints (up to 6 hours) post-dose
    End point values
    Orteronel + Prednisone
    Number of subjects analysed
    50
    Units: nanogram per milliliter (ng/mL)
    arithmetic mean (standard deviation)
        Orteronel: Cycle 1 Day 1 (n=50)
    1904 ± 1000.98
        Orteronel: Cycle 2 Day 1 (n=44)
    3017.9 ± 1512.33
        M-I metabolite: Cycle 1 Day 1 (n=50)
    263.5 ± 161.22
        M-I metabolite: Cycle 2 Day 1 (n=44)
    597.5 ± 333.39
    No statistical analyses for this end point

    Secondary: Number of Subjects Reporting One or More Treatment-emergent Adverse Events

    Close Top of page
    End point title
    Number of Subjects Reporting One or More Treatment-emergent Adverse Events
    End point description
    An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation subject administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. Safety analysis set was defined as all subjects who received at least 1 dose of any study drug.
    End point type
    Secondary
    End point timeframe
    Baseline up to 30 days after last dose of study drug (Day 86)
    End point values
    Orteronel + Prednisone
    Number of subjects analysed
    50
    Units: subjects
        number (not applicable)
    48
    No statistical analyses for this end point

    Secondary: Number of Subjects Reporting Clinically Significant Abnormalities in Vital Signs

    Close Top of page
    End point title
    Number of Subjects Reporting Clinically Significant Abnormalities in Vital Signs
    End point description
    The number of subjects with any clinically significant abnormalities in vital signs collected throughout study. Vital signs included body temperature (oral), sitting blood pressure (after the subject has rested for at least 5 minutes), and pulse (bpm). Safety analysis set was defined as all subjects who received at least 1 dose of any study drug.
    End point type
    Secondary
    End point timeframe
    Baseline up to 30 days after last dose of study drug (Day 86)
    End point values
    Orteronel + Prednisone
    Number of subjects analysed
    50
    Units: subjects
        number (not applicable)
    0
    No statistical analyses for this end point

    Secondary: Number of Subjects Reporting Clinically Significant Abnormalities in Laboratory Values

    Close Top of page
    End point title
    Number of Subjects Reporting Clinically Significant Abnormalities in Laboratory Values
    End point description
    The number of subjects with any clinically significant abnormalities in safety laboratory values collected throughout study. Safety analysis set was defined as all subjects who received at least 1 dose of any study drug.
    End point type
    Secondary
    End point timeframe
    Baseline up to 30 days after last dose of study drug (Day 86)
    End point values
    Orteronel + Prednisone
    Number of subjects analysed
    50
    Units: subjects
        number (not applicable)
    5
    No statistical analyses for this end point

    Secondary: Number of Subjects Reporting Clinically Significant Abnormalities in Physical Findings

    Close Top of page
    End point title
    Number of Subjects Reporting Clinically Significant Abnormalities in Physical Findings
    End point description
    Physical examination consists of examinations of the following body systems: (1) eyes; (2) ears, nose, throat; (3) cardiovascular system; (4) respiratory system; (5) gastrointestinal system; (6) dermatologic system; (7) extremities; (8) musculoskeletal system; (9) nervous system; (10) lymph nodes; and (11) physical examinations other than body systems described in (1) to (10). Safety analysis set was defined as all subjects who received at least 1 dose of any study drug.
    End point type
    Secondary
    End point timeframe
    Baseline up to 30 days after last dose of study drug (Day 86)
    End point values
    Orteronel + Prednisone
    Number of subjects analysed
    50
    Units: subjects
        number (not applicable)
    0
    No statistical analyses for this end point

    Secondary: Number of Subjects Reporting Clinically Significant Abnormalities in ECG

    Close Top of page
    End point title
    Number of Subjects Reporting Clinically Significant Abnormalities in ECG
    End point description
    The number of subjects who reported clinically significant abnormalities in ECG were measured throughout study. ECGs were performed after the subject had been supine for at least 10 minutes. Safety analysis set was defined as all subjects who received at least 1 dose of any study drug.
    End point type
    Secondary
    End point timeframe
    Baseline up to 30 days after last dose of study drug (Day 86)
    End point values
    Orteronel + Prednisone
    Number of subjects analysed
    50
    Units: subjects
        number (not applicable)
    0
    No statistical analyses for this end point

    Adverse events

    Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 30 days after the last dose of double-blind study drug (Day 86).
    Adverse event reporting additional description
    At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the subject or observed by the investigator was recorded, irrespective of the relation to study treatment.
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    15.0
    Reporting groups
    Reporting group title
    Orteronel + Prednisone
    Reporting group description
    Orteronel 400 mg, tablets, orally, twice daily along with prednisone 5 mg, tablets, orally, twice daily for 2 treatment cycles of 28 days each. Gonadotropin-releasing hormone analogue therapy was supplied as a commercially available dosage formulation.

    Serious adverse events
    Orteronel + Prednisone
    Total subjects affected by serious adverse events
         subjects affected / exposed
    17 / 50 (34.00%)
         number of deaths (all causes)
    0
         number of deaths resulting from adverse events
    0
    Vascular disorders
    Deep vein thrombosis
         subjects affected / exposed
    2 / 50 (4.00%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Investigations
    Blood glucose increased
         subjects affected / exposed
    1 / 50 (2.00%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Cardiac disorders
    Angina pectoris
         subjects affected / exposed
    1 / 50 (2.00%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    1 / 50 (2.00%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Pneumonitis
         subjects affected / exposed
    1 / 50 (2.00%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Lung disorder
         subjects affected / exposed
    2 / 50 (4.00%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Pumonary embolism
         subjects affected / exposed
    5 / 50 (10.00%)
         occurrences causally related to treatment / all
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    Nervous system disorders
    Cerebrovascular disorder
         subjects affected / exposed
    1 / 50 (2.00%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Spinal cord compression
         subjects affected / exposed
    1 / 50 (2.00%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    General disorders and administration site conditions
    Non-cardiac chest pain
         subjects affected / exposed
    1 / 50 (2.00%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Gastrointestinal disorders
    Pancreatitis
         subjects affected / exposed
    1 / 50 (2.00%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Diarrhoea
         subjects affected / exposed
    1 / 50 (2.00%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Proctitis haemorrhagic
         subjects affected / exposed
    1 / 50 (2.00%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Nausea
         subjects affected / exposed
    1 / 50 (2.00%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Renal and urinary disorders
    Renal failure
         subjects affected / exposed
    2 / 50 (4.00%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Metabolism and nutrition disorders
    Hyperglycaemia
         subjects affected / exposed
    1 / 50 (2.00%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Infections and infestations
    Bacteraemia
         subjects affected / exposed
    1 / 50 (2.00%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Septic shock
         subjects affected / exposed
    1 / 50 (2.00%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pneumonia pseudomonal
         subjects affected / exposed
    1 / 50 (2.00%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    1 / 50 (2.00%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Viral infection
         subjects affected / exposed
    1 / 50 (2.00%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pneumonia
         subjects affected / exposed
    1 / 50 (2.00%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Orteronel + Prednisone
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    48 / 50 (96.00%)
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    3 / 50 (6.00%)
         occurrences all number
    3
    Vascular disorders
    Hot flush
         subjects affected / exposed
    7 / 50 (14.00%)
         occurrences all number
    7
    Hypertension
         subjects affected / exposed
    3 / 50 (6.00%)
         occurrences all number
    4
    Investigations
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    5 / 50 (10.00%)
         occurrences all number
    7
    Weight decreased
         subjects affected / exposed
    9 / 50 (18.00%)
         occurrences all number
    9
    Alanine aminotransferase increased
         subjects affected / exposed
    3 / 50 (6.00%)
         occurrences all number
    3
    Blood lactate dehydrogenase increased
         subjects affected / exposed
    3 / 50 (6.00%)
         occurrences all number
    3
    Blood alkaline phosphatase increased
         subjects affected / exposed
    4 / 50 (8.00%)
         occurrences all number
    6
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    6 / 50 (12.00%)
         occurrences all number
    9
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    12 / 50 (24.00%)
         occurrences all number
    16
    Cough
         subjects affected / exposed
    3 / 50 (6.00%)
         occurrences all number
    3
    Dyspnoea exertional
         subjects affected / exposed
    3 / 50 (6.00%)
         occurrences all number
    3
    Upper respiratory tract infection
         subjects affected / exposed
    3 / 50 (6.00%)
         occurrences all number
    3
    Bronchitis
         subjects affected / exposed
    3 / 50 (6.00%)
         occurrences all number
    3
    Nervous system disorders
    Headache
         subjects affected / exposed
    5 / 50 (10.00%)
         occurrences all number
    5
    Dizziness
         subjects affected / exposed
    4 / 50 (8.00%)
         occurrences all number
    5
    Dysgeusia
         subjects affected / exposed
    4 / 50 (8.00%)
         occurrences all number
    5
    Paraesthesia
         subjects affected / exposed
    3 / 50 (6.00%)
         occurrences all number
    4
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    12 / 50 (24.00%)
         occurrences all number
    18
    Asthenia
         subjects affected / exposed
    11 / 50 (22.00%)
         occurrences all number
    13
    Oedema peripheral
         subjects affected / exposed
    3 / 50 (6.00%)
         occurrences all number
    3
    Psychiatric disorders
    Depression
         subjects affected / exposed
    6 / 50 (12.00%)
         occurrences all number
    6
    Gastrointestinal disorders
    Constipation
         subjects affected / exposed
    18 / 50 (36.00%)
         occurrences all number
    18
    Vomiting
         subjects affected / exposed
    7 / 50 (14.00%)
         occurrences all number
    10
    Diarrhoea
         subjects affected / exposed
    9 / 50 (18.00%)
         occurrences all number
    12
    Nausea
         subjects affected / exposed
    16 / 50 (32.00%)
         occurrences all number
    22
    Abdominal pain upper
         subjects affected / exposed
    5 / 50 (10.00%)
         occurrences all number
    5
    Abdominal pain
         subjects affected / exposed
    3 / 50 (6.00%)
         occurrences all number
    3
    Dry mouth
         subjects affected / exposed
    3 / 50 (6.00%)
         occurrences all number
    4
    Skin and subcutaneous tissue disorders
    Rash macular
         subjects affected / exposed
    4 / 50 (8.00%)
         occurrences all number
    5
    Musculoskeletal and connective tissue disorders
    Muscle spasms
         subjects affected / exposed
    9 / 50 (18.00%)
         occurrences all number
    13
    Muscular weakness
         subjects affected / exposed
    5 / 50 (10.00%)
         occurrences all number
    5
    Pain in extremity
         subjects affected / exposed
    4 / 50 (8.00%)
         occurrences all number
    5
    Arthralgia
         subjects affected / exposed
    4 / 50 (8.00%)
         occurrences all number
    4
    Back pain
         subjects affected / exposed
    11 / 50 (22.00%)
         occurrences all number
    12
    Bone pain
         subjects affected / exposed
    3 / 50 (6.00%)
         occurrences all number
    3
    Musculoskeletal chest pain
         subjects affected / exposed
    3 / 50 (6.00%)
         occurrences all number
    4
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    10 / 50 (20.00%)
         occurrences all number
    12
    Dehydration
         subjects affected / exposed
    5 / 50 (10.00%)
         occurrences all number
    5
    Diabetes mellitus
         subjects affected / exposed
    3 / 50 (6.00%)
         occurrences all number
    3
    Hypokalaemia
         subjects affected / exposed
    3 / 50 (6.00%)
         occurrences all number
    4

    More information

    Close Top of page

    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? No

    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
    As of 1.2.2020, the UK is no longer an EU Member State. However, EU law still applies to the UK during the transition period
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2020 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA