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   37527   clinical trials with a EudraCT protocol, of which   6154   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, 2-Stage, 2-Cohort Study of Talazoparib (BMN 673) Administered to Germline BRCA Mutation Subjects with Locally Advanced and/or Metastatic Breast Cancer

    Summary
    EudraCT number
    2013-003076-12
    Trial protocol
    GB   ES  
    Global end of trial date
    31 Oct 2018

    Results information
    Results version number
    v2(current)
    This version publication date
    07 Sep 2019
    First version publication date
    17 Sep 2017
    Other versions
    v1
    Version creation reason

    Trial information

    Close Top of page
    Trial identification
    Sponsor protocol code
    673-201
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT02034916
    WHO universal trial number (UTN)
    -
    Other trial identifiers
    Alias Study Number: C3441008
    Sponsors
    Sponsor organisation name
    Pfizer Inc.
    Sponsor organisation address
    235 E 42nd Street, New York, United States, NY 10017
    Public contact
    Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., 001 8007181021, ClinicalTrials.gov_Inquiries@pfizer.com
    Scientific contact
    Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., 001 8007181021, ClinicalTrials.gov_Inquiries@pfizer.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
    02 May 2019
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    31 Oct 2018
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To determine the objective response rate (ORR) for each cohort treated with talazoparib as a single agent. The ORR would be based on confirmed responses as defined by Response Evaluation Criteria in Solid Tumors (RECIST).
    Protection of trial subjects
    The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Council for Harmonization (ICH) Good Clinical Practice (GCP) Guidelines. All the local regulatory requirements pertinent to safety of trials subjects were followed.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    13 Dec 2013
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    France: 15
    Country: Number of subjects enrolled
    Germany: 18
    Country: Number of subjects enrolled
    Spain: 11
    Country: Number of subjects enrolled
    United Kingdom: 15
    Country: Number of subjects enrolled
    United States: 25
    Worldwide total number of subjects
    84
    EEA total number of subjects
    59
    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)
    70
    From 65 to 84 years
    14
    85 years and over
    0

    Subject disposition

    Close Top of page
    Recruitment
    Recruitment details
    -

    Pre-assignment
    Screening details
    In this study, enrollment of subjects was to be done in 2 stages for each of the 2 cohorts. Sufficient responses in each cohort were observed such that enrollment could proceed to Stage 2 for both cohorts. However, due to Sponsor decision, enrollment in the overall trial was terminated early.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Cohort 1: Talazoparib 1 mg
    Arm description
    Subjects who responded to a prior platinum-containing treatment for metastatic breast cancer, received talazoparib 1.0 milligram (mg) orally, once daily for 21 days in repeated 21-day cycles until disease progression, occurrence of unacceptable toxicity or permanent treatment discontinuation. Subjects were followed-up for survival and new anticancer treatment at every 60 days after the last dose of study drug for the first year, every 90 days thereafter.
    Arm type
    Experimental

    Investigational medicinal product name
    Talazoparib
    Investigational medicinal product code
    Other name
    BMN 673, MDV3800
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Talazoparib 1 mg was administered orally, once daily.

    Arm title
    Cohort 2: Talazoparib 1 mg
    Arm description
    Subjects with more than 2 prior non-platinum chemotherapy treatment for metastatic breast cancer, received talazoparib 1.0 mg orally, once daily for 21 days in repeated 21-day cycles until disease progression, occurrence of unacceptable toxicity or permanent treatment discontinuation. Prior adjuvant or neo-adjuvant therapy with a platinum was allowed if first disease recurrence was for more than 6 months since last dose of adjuvant/neo-adjuvant platinum treatment. Subjects were followed-up for survival and new anticancer treatment at every 60 days after the last dose of study drug for the first year, every 90 days thereafter.
    Arm type
    Experimental

    Investigational medicinal product name
    Talazoparib
    Investigational medicinal product code
    Other name
    BMN 673, MDV3800
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Talazoparib 1 mg was administered orally, once daily.

    Number of subjects in period 1
    Cohort 1: Talazoparib 1 mg Cohort 2: Talazoparib 1 mg
    Started
    49
    35
    Treated
    48
    35
    Completed
    0
    0
    Not completed
    49
    35
         Death
    39
    28
         Study terminated by sponsor
    4
    5
         Consent withdrawn by subject
    2
    1
         Lost to follow-up
    4
    1

    Baseline characteristics

    Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Cohort 1: Talazoparib 1 mg
    Reporting group description
    Subjects who responded to a prior platinum-containing treatment for metastatic breast cancer, received talazoparib 1.0 milligram (mg) orally, once daily for 21 days in repeated 21-day cycles until disease progression, occurrence of unacceptable toxicity or permanent treatment discontinuation. Subjects were followed-up for survival and new anticancer treatment at every 60 days after the last dose of study drug for the first year, every 90 days thereafter.

    Reporting group title
    Cohort 2: Talazoparib 1 mg
    Reporting group description
    Subjects with more than 2 prior non-platinum chemotherapy treatment for metastatic breast cancer, received talazoparib 1.0 mg orally, once daily for 21 days in repeated 21-day cycles until disease progression, occurrence of unacceptable toxicity or permanent treatment discontinuation. Prior adjuvant or neo-adjuvant therapy with a platinum was allowed if first disease recurrence was for more than 6 months since last dose of adjuvant/neo-adjuvant platinum treatment. Subjects were followed-up for survival and new anticancer treatment at every 60 days after the last dose of study drug for the first year, every 90 days thereafter.

    Reporting group values
    Cohort 1: Talazoparib 1 mg Cohort 2: Talazoparib 1 mg Total
    Number of subjects
    49 35 84
    Age categorical
    Units: Subjects
        In utero
    0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    0 0 0
        Newborns (0-27 days)
    0 0 0
        Infants and toddlers (28 days-23 months)
    0 0 0
        Children (2-11 years)
    0 0 0
        Adolescents (12-17 years)
    0 0 0
        Adults (18-64 years)
    42 28 70
        From 65-84 years
    7 7 14
        85 years and over
    0 0 0
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    50.1 ± 11.48 53.4 ± 11.05 -
    Gender, Male/Female
    Units: Subjects
        Female
    48 34 82
        Male
    1 1 2
    Subject analysis sets

    Subject analysis set title
    All Subjects: Talazoparib 1 mg
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Subjects, who either responded to a prior platinum-containing treatment for metastatic breast cancer or had more than 2 prior non-platinum chemotherapy treatment for metastatic breast cancer, received talazoparib 1.0 mg orally, once daily for 21 days in repeated 21-day cycles until disease progression, occurrence of unacceptable toxicity or permanent treatment discontinuation. For the subjects with non-platinum chemotherapy, prior adjuvant or neo-adjuvant therapy with a platinum was allowed if first disease recurrence was for more than 6 months since last dose of adjuvant/neo-adjuvant platinum treatment. Subjects were followed-up for survival and new anticancer treatment at every 60 days after the last dose of study drug for the first year, every 90 days thereafter.

    Subject analysis sets values
    All Subjects: Talazoparib 1 mg
    Number of subjects
    83
    Age categorical
    Units: Subjects
        In utero
        Preterm newborn infants (gestational age < 37 wks)
        Newborns (0-27 days)
        Infants and toddlers (28 days-23 months)
        Children (2-11 years)
        Adolescents (12-17 years)
        Adults (18-64 years)
        From 65-84 years
        85 years and over
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    51.5 ± 11.35
    Gender, Male/Female
    Units: Subjects
        Female
        Male

    End points

    Close Top of page
    End points reporting groups
    Reporting group title
    Cohort 1: Talazoparib 1 mg
    Reporting group description
    Subjects who responded to a prior platinum-containing treatment for metastatic breast cancer, received talazoparib 1.0 milligram (mg) orally, once daily for 21 days in repeated 21-day cycles until disease progression, occurrence of unacceptable toxicity or permanent treatment discontinuation. Subjects were followed-up for survival and new anticancer treatment at every 60 days after the last dose of study drug for the first year, every 90 days thereafter.

    Reporting group title
    Cohort 2: Talazoparib 1 mg
    Reporting group description
    Subjects with more than 2 prior non-platinum chemotherapy treatment for metastatic breast cancer, received talazoparib 1.0 mg orally, once daily for 21 days in repeated 21-day cycles until disease progression, occurrence of unacceptable toxicity or permanent treatment discontinuation. Prior adjuvant or neo-adjuvant therapy with a platinum was allowed if first disease recurrence was for more than 6 months since last dose of adjuvant/neo-adjuvant platinum treatment. Subjects were followed-up for survival and new anticancer treatment at every 60 days after the last dose of study drug for the first year, every 90 days thereafter.

    Subject analysis set title
    All Subjects: Talazoparib 1 mg
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Subjects, who either responded to a prior platinum-containing treatment for metastatic breast cancer or had more than 2 prior non-platinum chemotherapy treatment for metastatic breast cancer, received talazoparib 1.0 mg orally, once daily for 21 days in repeated 21-day cycles until disease progression, occurrence of unacceptable toxicity or permanent treatment discontinuation. For the subjects with non-platinum chemotherapy, prior adjuvant or neo-adjuvant therapy with a platinum was allowed if first disease recurrence was for more than 6 months since last dose of adjuvant/neo-adjuvant platinum treatment. Subjects were followed-up for survival and new anticancer treatment at every 60 days after the last dose of study drug for the first year, every 90 days thereafter.

    Primary: Objective Response Rate (ORR)

    Close Top of page
    End point title
    Objective Response Rate (ORR) [1]
    End point description
    ORR: Percentage of subjects with a confirmed best overall complete response (CR) or partial response (PR) according to response evaluation criteria in solid tumors version 1.1 (RECIST 1.1), evaluated by an independent radiology facility (IRF). CR: Disappearance of all non-nodal target and non-target lesions, including target and non-target lymph nodes reduction to less than 10 millimeter (mm) in short axis. PR: Greater than or equal to (>=) 30 percent (%) decrease in sum of diameters of target lesions, compared to the sum at baseline. Tumor-evaluable population (TEP) included all treated subjects who had a baseline and at least 1 post-baseline tumor assessment or who discontinued the study before first scheduled post-baseline tumor scan plus (+) 1 week window.
    End point type
    Primary
    End point timeframe
    From randomization until data cutoff date (01 Sep 2016)
    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: No statistical analysis was performed for this endpoint
    End point values
    Cohort 1: Talazoparib 1 mg Cohort 2: Talazoparib 1 mg
    Number of subjects analysed
    48
    35
    Units: percentage of subjects
        number (confidence interval 95%)
    20.8 (10.47 to 34.99)
    37.1 (21.47 to 55.08)
    No statistical analyses for this end point

    Secondary: Clinical Benefit Rate-24 (CBR-24)

    Close Top of page
    End point title
    Clinical Benefit Rate-24 (CBR-24)
    End point description
    CBR24: Percentage of subjects with a best overall response of confirmed CR, confirmed PR or stable disease (SD) sustained for at least 24 weeks, as assessed by IRF using RECIST 1.1. CR: Disappearance of all non-nodal target and non-target lesions, including target and non-target lymph nodes reduction to less than 10 mm in short axis. PR: >=30% decrease in sum of diameters of target lesions, compared to the sum at baseline. SD: Neither PR nor progression of disease (PD) criteria met. SD follow PR only when sum increases by less than 20% from the nadir, but previously seen 30% decrease from baseline no longer hold. PD: >=20% increase (>=5 mm absolute increase) in the sum of target lesion measurements, compared to the smallest sum on study (including baseline), or unequivocal progression of non-target lesions, evaluated as a whole, such that it is clear that treatment has failed and disease is progressing, regardless of the status of the target lesions. Analysis was done on TEP.
    End point type
    Secondary
    End point timeframe
    From randomization until data cutoff date (01 Sep 2016)
    End point values
    Cohort 1: Talazoparib 1 mg Cohort 2: Talazoparib 1 mg
    Number of subjects analysed
    48
    35
    Units: percentage of subjects
        number (confidence interval 95%)
    27.1 (15.28 to 41.85)
    45.7 (28.83 to 63.35)
    No statistical analyses for this end point

    Secondary: Duration of Response (DOR)

    Close Top of page
    End point title
    Duration of Response (DOR)
    End point description
    DOR: Time from first documentation of CR or PR, to PD by IRF using RECIST 1.1, or to death (any cause), whichever occurred first. CR: Disappearance of all non-nodal target, non-target lesions (lymph nodes reduction to less than (<) 10 mm in short axis). PR: >=30% decrease in sum of diameters of target lesions, compared baseline sum. PD: >=20% increase (>=5 mm absolute increase) in sum of target lesion, compared to smallest sum, or unequivocal progression of non-target lesions, regardless target lesions. Subjects with no PD or death were censored at last tumor assessment prior to on or before of new anticancer therapy or before data cutoff. Analysis was done on TEP. Here 'Number of subjects analyzed' signifies subjects evaluable for this endpoint and '99999' signifies data not available as upper limit of 95% confidence interval (CI) was not reached due to very less number of subjects and insufficient events at data cutoff.
    End point type
    Secondary
    End point timeframe
    From first documentation of CR or PR until PD, last tumor assessment without PD before new anticancer treatment initiation or death due to any cause, whichever occurred first (up to the data cutoff date [01 Sep 2016])
    End point values
    Cohort 1: Talazoparib 1 mg Cohort 2: Talazoparib 1 mg
    Number of subjects analysed
    10
    13
    Units: months
        median (confidence interval 95%)
    5.8 (2.8 to 99999)
    3.8 (2.8 to 10.1)
    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: Time, in months, from the first dose of study drug to the first documentation of PD by investigator assessment using RECIST 1.1 or death due to any cause on or before the data cutoff date, whichever occurred first. PD: >=20% increase (>=5 mm absolute increase) in the sum of target lesion measurements, compared to the smallest sum on study (including baseline), or unequivocal progression of non-target lesions, evaluated as a whole, such that it is clear that treatment has failed and disease is progressing, regardless of the status of the target lesions. Subjects with no PFS event at the analysis were censored at last tumor assessment date prior to data cutoff or date of new anticancer treatment initiation, whichever occurred first. ITT population involved all enrolled subjects including subjects who were not treated.
    End point type
    Secondary
    End point timeframe
    From first dose of study drug until PD, last tumor assessment without PD before new anticancer treatment initiation or death due to any cause, whichever occurred first (up to the data cutoff date [01 Sep 2016])
    End point values
    Cohort 1: Talazoparib 1 mg Cohort 2: Talazoparib 1 mg
    Number of subjects analysed
    49
    35
    Units: months
        median (confidence interval 95%)
    4.0 (2.8 to 5.4)
    5.6 (5.5 to 7.8)
    No statistical analyses for this end point

    Secondary: Overall Survival (OS)

    Close Top of page
    End point title
    Overall Survival (OS)
    End point description
    OS was defined as the time from first dose of study drug to death due to any cause. For subjects without a death date at the time of data cutoff or permanently lost to follow-up, OS was right-censored at the date the subject was last known to be alive on or before the data cutoff date. ITT population. Here ‘99999’ signifies data not available due to insufficient number of events at data cutoff.
    End point type
    Secondary
    End point timeframe
    From first dose of study drug until death due to any cause (up to the data cutoff date [01 Sep 2016])
    End point values
    Cohort 1: Talazoparib 1 mg Cohort 2: Talazoparib 1 mg
    Number of subjects analysed
    49
    35
    Units: months
        median (confidence interval 95%)
    11.8 (8.8 to 15.0)
    16.5 (10.1 to 99999)
    No statistical analyses for this end point

    Secondary: Number of Subjects With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

    Close Top of page
    End point title
    Number of Subjects With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
    End point description
    An AE was any untoward medical occurrence in a subject who received study drug without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; an important medical event or reaction, including events requiring medical intervention to prevent worsening to any of the previously noted seriousness criteria. A treatment emergent AE was defined as an event that emerged during the treatment period that was absent before treatment, or worsened during the treatment period relative to the pretreatment state. AEs included both serious and non-serious AEs. Safety population included all subjects who received at least 1 dose of talazoparib.
    End point type
    Secondary
    End point timeframe
    Baseline up to end of study (up to a maximum duration of 42.8 months): based on data cutoff date (31 Oct 2018)
    End point values
    Cohort 1: Talazoparib 1 mg Cohort 2: Talazoparib 1 mg
    Number of subjects analysed
    48
    35
    Units: subjects
        AEs
    47
    34
        SAEs
    16
    7
    No statistical analyses for this end point

    Secondary: Number of Subjects With Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs)

    Close Top of page
    End point title
    Number of Subjects With Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs)
    End point description
    A treatment-related AE was any untoward medical occurrence attributed to study drug in a subject who received study drug. A treatment-related SAE was a treatment-related AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; an important medical event or reaction, including events requiring medical intervention to prevent worsening to any of the previously noted seriousness criteria. Safety population included all subjects who received at least 1 dose of talazoparib. Related TEAEs are TEAEs that were judged by the investigators as possibly, probably, or definitely related to study drug. AEs included both SAES and non SAES.
    End point type
    Secondary
    End point timeframe
    Baseline up to end of study (up to a maximum duration of 42.8 months): based on data cutoff date (31 Oct 2018)
    End point values
    Cohort 1: Talazoparib 1 mg Cohort 2: Talazoparib 1 mg
    Number of subjects analysed
    48
    35
    Units: subjects
        AEs
    46
    33
        SAEs
    7
    4
    No statistical analyses for this end point

    Secondary: Number of Subjects With Outcome in Response to Adverse Events (AEs)

    Close Top of page
    End point title
    Number of Subjects With Outcome in Response to Adverse Events (AEs)
    End point description
    An AE was any untoward medical occurrence in a subject who received study drug without regard to possibility of causal relationship. Outcome of an AE was response to a question answered by the investigator: ‘Is the AE leading to study discontinuation or death?’ as ‘yes’. Safety population included all subjects who received at least 1 dose of talazoparib.
    End point type
    Secondary
    End point timeframe
    Baseline up to end of study (up to a maximum duration of 42.8 months): based on data cutoff date (31 Oct 2018)
    End point values
    Cohort 1: Talazoparib 1 mg Cohort 2: Talazoparib 1 mg
    Number of subjects analysed
    48
    35
    Units: subjects
        AEs leading to study drug discontinuation
    4
    1
        AEs leading to death
    5
    1
    No statistical analyses for this end point

    Secondary: Number of Subjects With Toxicity Grades Increase of 2 or More in Laboratory Parameter (Hematology Parameter)

    Close Top of page
    End point title
    Number of Subjects With Toxicity Grades Increase of 2 or More in Laboratory Parameter (Hematology Parameter)
    End point description
    Laboratory tests included hematology (hemoglobin [low], leucocytes [low], lymphocytes [low], neutrophils [low], platelets [low]). Toxicity grades were evaluated based on national cancer institute- common terminology criteria for adverse events (NCI-CTCAE) version 4.03. Number of subjects with increase of 2 or more CTCAE toxicity grades above baseline, for hematology laboratory parameter is reported in this endpoint. Safety population included all subjects who received at least 1 dose of talazoparib.
    End point type
    Secondary
    End point timeframe
    Baseline up to end of study (up to a maximum duration of 42.8 months): based on data cutoff date (31 Oct 2018)
    End point values
    Cohort 1: Talazoparib 1 mg Cohort 2: Talazoparib 1 mg
    Number of subjects analysed
    48
    35
    Units: subjects
        Hemoglobin (low)
    19
    16
        Leukocytes (low)
    16
    15
        Lymphocytes (low)
    15
    4
        Neutrophils (low)
    20
    17
        Platelets (low)
    21
    10
    No statistical analyses for this end point

    Secondary: Number of Subjects With Toxicity Grades Increase of 2 or More in Laboratory Parameter (Chemistry Parameter)

    Close Top of page
    End point title
    Number of Subjects With Toxicity Grades Increase of 2 or More in Laboratory Parameter (Chemistry Parameter)
    End point description
    Laboratory tests included serum chemistry (alanine aminotransferase [high], albumin [low], alkaline phosphatase [high], aspartate aminotransferase [high], bilirubin [high], calcium [low], glucose [high], magnesium [low], phosphate [low], potassium [high], potassium [low], sodium [high], sodium [low]). Toxicity grades were evaluated based on national cancer institute- common terminology criteria for adverse events (NCI-CTCAE) version 4.03. Number of subjects with increase of 2 or more CTCAE toxicity grades above baseline, for chemistry laboratory parameter is reported in this endpoint. Safety population included all subjects who received at least 1 dose of talazoparib.
    End point type
    Secondary
    End point timeframe
    Baseline up to 30 days after the last dose of study drug or before initiation of a new anticancer treatment, whichever occurred first (up to data cutoff date [01 Sep 2016])
    End point values
    Cohort 1: Talazoparib 1 mg Cohort 2: Talazoparib 1 mg
    Number of subjects analysed
    48
    35
    Units: subjects
        Alanine aminotransferase (high)
    3
    2
        Albumin (low)
    3
    0
        Alkaline phosphatase (high)
    1
    1
        Aspartate aminotransferase (high)
    2
    1
        Bilirubin (high)
    2
    0
        Calcium (low)
    4
    1
        Glucose (high)
    1
    1
        Magnesium (low)
    1
    0
        Phosphate (low)
    6
    2
        Potassium (high)
    1
    0
        Potassium (low)
    2
    0
        Sodium (high)
    1
    0
        Sodium (low)
    0
    1
    No statistical analyses for this end point

    Secondary: Number of Subjects With Clinically Significant Change From Baseline in Vital Signs

    Close Top of page
    End point title
    Number of Subjects With Clinically Significant Change From Baseline in Vital Signs
    End point description
    Criteria for clinically significant vital signs changes: 1) Blood pressure: systolic blood pressure (SBP): greater than or equal to (>=30) millimeters of mercury (mmHg) increase from baseline, diastolic blood pressure (DBP): >=20 mmHg decrease from baseline; 2) Heart rate (HR): absolute HR greater than (>) 120 beats per minute (bpm) and >30 bpm increase from baseline, absolute HR less than (<) 50 bpm and >20 bpm decrease from baseline; 3) Weight: >10 percent (%) decrease from baseline. Number of subjects with any clinically significant change from baseline for blood pressure, heart rate and weight are reported in this endpoint. Safety population included all subjects who received at least 1 dose of talazoparib.
    End point type
    Secondary
    End point timeframe
    Baseline up to end of study (up to a maximum duration of 42.8 months): based on data cutoff date (31 Oct 2018)
    End point values
    Cohort 1: Talazoparib 1 mg Cohort 2: Talazoparib 1 mg
    Number of subjects analysed
    48
    35
    Units: subjects
        Blood pressure (SBP or DBP)
    20
    18
        HR
    2
    0
        Weight
    4
    1
    No statistical analyses for this end point

    Secondary: Number of Subjects With Clinically Significant Change From Baseline in Physical Findings

    Close Top of page
    End point title
    Number of Subjects With Clinically Significant Change From Baseline in Physical Findings
    End point description
    Physical examination included examination of the head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, gastrointestinal, musculoskeletal, and neurological systems. The examination assessed the subjects for any potential changes in general appearance, the respiratory and cardiovascular systems, as well as towards subject reported symptoms. Findings were considered to be clinically significant based on investigator’s decision. Safety population included all subjects who received at least 1 dose of talazoparib.
    End point type
    Secondary
    End point timeframe
    Baseline up to end of study (up to a maximum duration of 42.8 months): based on data cutoff date (31 Oct 2018)
    End point values
    Cohort 1: Talazoparib 1 mg Cohort 2: Talazoparib 1 mg
    Number of subjects analysed
    48
    35
    Units: subjects
    0
    0
    No statistical analyses for this end point

    Secondary: Number of Subjects With At Least 1 Concomitant Medication

    Close Top of page
    End point title
    Number of Subjects With At Least 1 Concomitant Medication
    End point description
    Number of subjects taking any non-study medications, therapies, including herbal supplements during the treatment-emergent period for the management of an adverse event or for the treatment of any other disease. Safety population included all subjects who received at least 1 dose of talazoparib.
    End point type
    Secondary
    End point timeframe
    Baseline up to end of study (up to a maximum duration of 42.8 months): based on data cutoff date (31 Oct 2018)
    End point values
    Cohort 1: Talazoparib 1 mg Cohort 2: Talazoparib 1 mg
    Number of subjects analysed
    48
    35
    Units: subjects
    48
    34
    No statistical analyses for this end point

    Secondary: Trough Concentration Versus Time Summary of Talazoparib

    Close Top of page
    End point title
    Trough Concentration Versus Time Summary of Talazoparib
    End point description
    Concentrations below the limit of quantitation values less than or equal to (<=) 25 picogram per milliliter (pg/mL) were set as zero. Pharmacokinetic (PK) analysis was not done separately for each reporting arm and cohorts were combined for PK analysis. PK population included all subjects who received at least 1 dose of talazoparib and had evaluable PK assessments. Here 'n' signifies subjects evaluable for each specified categories.
    End point type
    Secondary
    End point timeframe
    Predose on Day 1 of Cycle 1, 2, 3, and 4 (data cutoff date: 01 Sep 2016)
    End point values
    All Subjects: Talazoparib 1 mg
    Number of subjects analysed
    83
    Units: pg/mL
    arithmetic mean (standard deviation)
        Day 1 of Cycle 1 (n = 82)
    10.3 ± 93.3
        Day 1 of Cycle 2 (n = 63)
    4340 ± 2360
        Day 1 of Cycle 3 (n = 44)
    4510 ± 2720
        Day 1 of Cycle 4 (n = 33)
    3660 ± 1690
    No statistical analyses for this end point

    Other pre-specified: Time to Deterioration in Global Health Status/Quality of Life (QOL) and Functional Status as Assessed by European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30)

    Close Top of page
    End point title
    Time to Deterioration in Global Health Status/Quality of Life (QOL) and Functional Status as Assessed by European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30)
    End point description
    Time to deterioration was defined as the time from baseline to day to death, first occurrence of progression, or a >=10 point change from baseline in any of the functional status score and global health status/QOL score based on the EORTC-QLQ-C30, whichever occurred first. EORTC-QLQ-C30 questionnaire is a standardized instrument developed to assess the quality of life of people with cancer. EORTC-QLQ-C30 functional subscale includes 5 items: physical, role, emotional, cognitive, and social functioning. All of the single items of functional status subscale measures and global health status/QOL subscale range from 0 to 100, where higher scores represent a better level of functioning/quality of life. ITT population involved all enrolled subjects including subjects who were not treated.
    End point type
    Other pre-specified
    End point timeframe
    Baseline up to death, disease progression or end of treatment (30 days after last dose of study drug or before initiation of a new anticancer therapy, whichever occurred first [up to data cutoff date: 01 Sep 2016])
    End point values
    Cohort 1: Talazoparib 1 mg Cohort 2: Talazoparib 1 mg
    Number of subjects analysed
    49
    35
    Units: months
    median (confidence interval 95%)
        Global Health Status/QOL
    2.8 (2.1 to 3.0)
    5.5 (4.2 to 5.7)
        Physical Functioning
    3.1 (2.1 to 4.6)
    5.6 (5.3 to 7.7)
        Role Functioning
    2.1 (1.4 to 2.8)
    4.2 (2.1 to 5.5)
        Emotional Functioning
    2.7 (2.0 to 2.8)
    5.5 (4.3 to 5.6)
        Cognitive Functioning
    2.7 (1.6 to 3.2)
    4.2 (2.8 to 5.5)
        Social Functioning
    2.2 (1.4 to 2.9)
    5.3 (4.1 to 5.6)
    No statistical analyses for this end point

    Other pre-specified: Time to Deterioration in Disease Specific Symptoms as Assessed by the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Breast Cancer Module (EORTC-QLQ-BR23)

    Close Top of page
    End point title
    Time to Deterioration in Disease Specific Symptoms as Assessed by the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Breast Cancer Module (EORTC-QLQ-BR23)
    End point description
    Time to deterioration was defined as the time from baseline to day to death, first occurrence of progression, or a >=10 point change from baseline in any of the symptom score based on the EORTC-QLQ-BR23, whichever occurred first. EORTC-QLQ-BR23 is a disease-specific module for breast cancer developed as a supplement for the EORTC-QLQ-C30 to assess the quality of life of subjects with breast cancer. EORTC-QLQ-BR23 symptoms subscale includes 4 items: systemic therapy side effects, breast symptoms, arm symptoms, upset by hair loss. Each item is rated by choosing 1 of 4 possible responses that record the level of intensity (1= not at all, 2= a little, 3= quite a bit, and 4= very much) within each scale. ITT population involved all enrolled subjects including subjects who were not treated.
    End point type
    Other pre-specified
    End point timeframe
    Baseline up to death, disease progression or end of treatment (30 days after last dose of study drug or before initiation of a new anticancer therapy, whichever occurred first [up to data cutoff date: 01 Sep 2016])
    End point values
    Cohort 1: Talazoparib 1 mg Cohort 2: Talazoparib 1 mg
    Number of subjects analysed
    49
    35
    Units: months
    median (confidence interval 95%)
        Systemic Therapy Side Effects
    2.8 (2.3 to 4.0)
    5.5 (4.1 to 5.6)
        Breast Symptoms
    3.1 (2.5 to 4.6)
    5.6 (5.3 to 7.7)
        Arm Symptoms
    2.6 (2.0 to 3.7)
    4.2 (2.8 to 5.5)
        Upset by Hair Loss
    4.0 (2.7 to 5.4)
    5.6 (5.3 to 7.7)
    No statistical analyses for this end point

    Adverse events

    Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Baseline up to end of study (up to maximum duration of 42.8 months)
    Adverse event reporting additional description
    Same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study. AEs and SAEs were collected for safety population.
    Assessment type
    Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    20.0
    Reporting groups
    Reporting group title
    Cohort 1: Talazoparib 1 mg
    Reporting group description
    Subjects who responded to a prior platinum-containing treatment for metastatic breast cancer, received talazoparib 1.0 mg orally, once daily for 21 days in repeated 21-day cycles until disease progression, occurrence of unacceptable toxicity or permanent treatment discontinuation. Subjects were followed-up for survival and new anticancer treatment at every 60 days after the last dose of study drug for the first year, every 90 days thereafter.

    Reporting group title
    Cohort 2: Talazoparib 1 mg
    Reporting group description
    Subjects with more than 2 prior non-platinum chemotherapy treatment for metastatic breast cancer, received talazoparib 1.0 mg orally, once daily for 21 days in repeated 21-day cycles until disease progression, occurrence of unacceptable toxicity or permanent treatment discontinuation. Prior adjuvant or neo-adjuvant therapy with a platinum was allowed if first disease recurrence was for more than 6 months since last dose of adjuvant/neo-adjuvant platinum treatment. Subjects were followed-up for survival and new anticancer treatment at every 60 days after the last dose of study drug for the first year, every 90 days thereafter.

    Serious adverse events
    Cohort 1: Talazoparib 1 mg Cohort 2: Talazoparib 1 mg
    Total subjects affected by serious adverse events
         subjects affected / exposed
    16 / 48 (33.33%)
    7 / 35 (20.00%)
         number of deaths (all causes)
    5
    1
         number of deaths resulting from adverse events
    Injury, poisoning and procedural complications
    Transfusion reaction
         subjects affected / exposed
    1 / 48 (2.08%)
    0 / 35 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Surgical and medical procedures
    Lipoinjection
         subjects affected / exposed
    1 / 48 (2.08%)
    0 / 35 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Salpingo-oophorectomy
    Additional description: Gender specific event.
         subjects affected / exposed
    1 / 48 (2.08%)
    0 / 35 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Platelet count decreased
         subjects affected / exposed
    1 / 48 (2.08%)
    1 / 35 (2.86%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Neoplasm progression
         subjects affected / exposed
    3 / 48 (6.25%)
    0 / 35 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 3
    0 / 1
    Breast cancer metastatic
         subjects affected / exposed
    2 / 48 (4.17%)
    0 / 35 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Silicon granuloma
         subjects affected / exposed
    1 / 48 (2.08%)
    0 / 35 (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
    Pleural effusion
         subjects affected / exposed
    3 / 48 (6.25%)
    2 / 35 (5.71%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    2 / 48 (4.17%)
    2 / 35 (5.71%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 5
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Atelectasis
         subjects affected / exposed
    1 / 48 (2.08%)
    0 / 35 (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
    1 / 48 (2.08%)
    0 / 35 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory distress
         subjects affected / exposed
    0 / 48 (0.00%)
    1 / 35 (2.86%)
         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
    5 / 48 (10.42%)
    1 / 35 (2.86%)
         occurrences causally related to treatment / all
    4 / 5
    3 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    2 / 48 (4.17%)
    1 / 35 (2.86%)
         occurrences causally related to treatment / all
    2 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anaemia of malignant disease
         subjects affected / exposed
    1 / 48 (2.08%)
    0 / 35 (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
    Central nervous system lesion
         subjects affected / exposed
    1 / 48 (2.08%)
    0 / 35 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Presyncope
         subjects affected / exposed
    1 / 48 (2.08%)
    0 / 35 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    1 / 48 (2.08%)
    0 / 35 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    1 / 48 (2.08%)
    0 / 35 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Oesophagitis
         subjects affected / exposed
    1 / 48 (2.08%)
    0 / 35 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    1 / 48 (2.08%)
    0 / 35 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Hypokalaemia
         subjects affected / exposed
    1 / 48 (2.08%)
    0 / 35 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Neutropenic sepsis
         subjects affected / exposed
    0 / 48 (0.00%)
    1 / 35 (2.86%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    2 / 48 (4.17%)
    0 / 35 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Influenza
         subjects affected / exposed
    0 / 48 (0.00%)
    1 / 35 (2.86%)
         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
    Cohort 1: Talazoparib 1 mg Cohort 2: Talazoparib 1 mg
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    47 / 48 (97.92%)
    34 / 35 (97.14%)
    Vascular disorders
    Hot flush
         subjects affected / exposed
    3 / 48 (6.25%)
    3 / 35 (8.57%)
         occurrences all number
    3
    3
    Lymphoedema
         subjects affected / exposed
    3 / 48 (6.25%)
    2 / 35 (5.71%)
         occurrences all number
    3
    2
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    3 / 48 (6.25%)
    10 / 35 (28.57%)
         occurrences all number
    7
    31
    Axillary pain
         subjects affected / exposed
    1 / 48 (2.08%)
    2 / 35 (5.71%)
         occurrences all number
    1
    4
    Fatigue
         subjects affected / exposed
    29 / 48 (60.42%)
    8 / 35 (22.86%)
         occurrences all number
    37
    15
    Mucosal inflammation
         subjects affected / exposed
    4 / 48 (8.33%)
    2 / 35 (5.71%)
         occurrences all number
    5
    2
    Non-cardiac chest pain
         subjects affected / exposed
    3 / 48 (6.25%)
    0 / 35 (0.00%)
         occurrences all number
    7
    0
    Oedema peripheral
         subjects affected / exposed
    1 / 48 (2.08%)
    6 / 35 (17.14%)
         occurrences all number
    1
    10
    Pyrexia
         subjects affected / exposed
    1 / 48 (2.08%)
    5 / 35 (14.29%)
         occurrences all number
    1
    9
    Chills
         subjects affected / exposed
    1 / 48 (2.08%)
    2 / 35 (5.71%)
         occurrences all number
    1
    2
    Psychiatric disorders
    Depression
         subjects affected / exposed
    1 / 48 (2.08%)
    2 / 35 (5.71%)
         occurrences all number
    1
    2
    Insomnia
         subjects affected / exposed
    5 / 48 (10.42%)
    3 / 35 (8.57%)
         occurrences all number
    5
    4
    Anxiety
         subjects affected / exposed
    2 / 48 (4.17%)
    2 / 35 (5.71%)
         occurrences all number
    2
    2
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    1 / 48 (2.08%)
    3 / 35 (8.57%)
         occurrences all number
    3
    6
    Aspartate aminotransferase increased
         subjects affected / exposed
    4 / 48 (8.33%)
    2 / 35 (5.71%)
         occurrences all number
    4
    5
    Neutrophil count decreased
         subjects affected / exposed
    5 / 48 (10.42%)
    5 / 35 (14.29%)
         occurrences all number
    11
    16
    Platelet count decreased
         subjects affected / exposed
    7 / 48 (14.58%)
    5 / 35 (14.29%)
         occurrences all number
    29
    16
    Weight decreased
         subjects affected / exposed
    3 / 48 (6.25%)
    0 / 35 (0.00%)
         occurrences all number
    3
    0
    White blood cell count decreased
         subjects affected / exposed
    3 / 48 (6.25%)
    5 / 35 (14.29%)
         occurrences all number
    13
    12
    Cardiac disorders
    Tachycardia
         subjects affected / exposed
    2 / 48 (4.17%)
    2 / 35 (5.71%)
         occurrences all number
    2
    2
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    23 / 48 (47.92%)
    19 / 35 (54.29%)
         occurrences all number
    67
    89
    Leukopenia
         subjects affected / exposed
    7 / 48 (14.58%)
    6 / 35 (17.14%)
         occurrences all number
    17
    21
    Lymphopenia
         subjects affected / exposed
    2 / 48 (4.17%)
    4 / 35 (11.43%)
         occurrences all number
    3
    8
    Neutropenia
         subjects affected / exposed
    10 / 48 (20.83%)
    12 / 35 (34.29%)
         occurrences all number
    36
    36
    Thrombocytopenia
         subjects affected / exposed
    18 / 48 (37.50%)
    9 / 35 (25.71%)
         occurrences all number
    49
    34
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    9 / 48 (18.75%)
    7 / 35 (20.00%)
         occurrences all number
    9
    12
    Dyspnoea
         subjects affected / exposed
    9 / 48 (18.75%)
    9 / 35 (25.71%)
         occurrences all number
    11
    22
    Epistaxis
         subjects affected / exposed
    2 / 48 (4.17%)
    2 / 35 (5.71%)
         occurrences all number
    2
    2
    Nasal congestion
         subjects affected / exposed
    1 / 48 (2.08%)
    2 / 35 (5.71%)
         occurrences all number
    1
    2
    Pleural effusion
         subjects affected / exposed
    1 / 48 (2.08%)
    2 / 35 (5.71%)
         occurrences all number
    1
    3
    Rhinorrhoea
         subjects affected / exposed
    0 / 48 (0.00%)
    3 / 35 (8.57%)
         occurrences all number
    0
    3
    Oropharyngeal pain
         subjects affected / exposed
    2 / 48 (4.17%)
    3 / 35 (8.57%)
         occurrences all number
    2
    3
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    6 / 48 (12.50%)
    2 / 35 (5.71%)
         occurrences all number
    7
    2
    Dysgeusia
         subjects affected / exposed
    1 / 48 (2.08%)
    3 / 35 (8.57%)
         occurrences all number
    1
    3
    Headache
         subjects affected / exposed
    9 / 48 (18.75%)
    11 / 35 (31.43%)
         occurrences all number
    14
    26
    Neuralgia
         subjects affected / exposed
    0 / 48 (0.00%)
    2 / 35 (5.71%)
         occurrences all number
    0
    2
    Neuropathy peripheral
         subjects affected / exposed
    2 / 48 (4.17%)
    4 / 35 (11.43%)
         occurrences all number
    2
    5
    Presyncope
         subjects affected / exposed
    0 / 48 (0.00%)
    2 / 35 (5.71%)
         occurrences all number
    0
    2
    Gastrointestinal disorders
    Abdominal discomfort
         subjects affected / exposed
    1 / 48 (2.08%)
    2 / 35 (5.71%)
         occurrences all number
    1
    2
    Abdominal distension
         subjects affected / exposed
    1 / 48 (2.08%)
    3 / 35 (8.57%)
         occurrences all number
    1
    4
    Abdominal pain
         subjects affected / exposed
    7 / 48 (14.58%)
    7 / 35 (20.00%)
         occurrences all number
    8
    14
    Abdominal pain upper
         subjects affected / exposed
    2 / 48 (4.17%)
    6 / 35 (17.14%)
         occurrences all number
    3
    13
    Constipation
         subjects affected / exposed
    9 / 48 (18.75%)
    6 / 35 (17.14%)
         occurrences all number
    10
    15
    Diarrhoea
         subjects affected / exposed
    18 / 48 (37.50%)
    10 / 35 (28.57%)
         occurrences all number
    26
    18
    Dry mouth
         subjects affected / exposed
    0 / 48 (0.00%)
    2 / 35 (5.71%)
         occurrences all number
    0
    2
    Dyspepsia
         subjects affected / exposed
    5 / 48 (10.42%)
    3 / 35 (8.57%)
         occurrences all number
    5
    4
    Nausea
         subjects affected / exposed
    20 / 48 (41.67%)
    15 / 35 (42.86%)
         occurrences all number
    24
    22
    Stomatitis
         subjects affected / exposed
    3 / 48 (6.25%)
    1 / 35 (2.86%)
         occurrences all number
    3
    1
    Toothache
         subjects affected / exposed
    1 / 48 (2.08%)
    2 / 35 (5.71%)
         occurrences all number
    1
    2
    Vomiting
         subjects affected / exposed
    10 / 48 (20.83%)
    8 / 35 (22.86%)
         occurrences all number
    19
    15
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    11 / 48 (22.92%)
    6 / 35 (17.14%)
         occurrences all number
    11
    6
    Dry skin
         subjects affected / exposed
    1 / 48 (2.08%)
    4 / 35 (11.43%)
         occurrences all number
    1
    5
    Erythema
         subjects affected / exposed
    0 / 48 (0.00%)
    3 / 35 (8.57%)
         occurrences all number
    0
    4
    Pruritus
         subjects affected / exposed
    1 / 48 (2.08%)
    3 / 35 (8.57%)
         occurrences all number
    1
    4
    Hyperhidrosis
         subjects affected / exposed
    1 / 48 (2.08%)
    2 / 35 (5.71%)
         occurrences all number
    1
    3
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    8 / 48 (16.67%)
    9 / 35 (25.71%)
         occurrences all number
    10
    14
    Back pain
         subjects affected / exposed
    12 / 48 (25.00%)
    8 / 35 (22.86%)
         occurrences all number
    13
    11
    Bone pain
         subjects affected / exposed
    0 / 48 (0.00%)
    2 / 35 (5.71%)
         occurrences all number
    0
    2
    Muscle spasms
         subjects affected / exposed
    4 / 48 (8.33%)
    5 / 35 (14.29%)
         occurrences all number
    4
    5
    Musculoskeletal chest pain
         subjects affected / exposed
    3 / 48 (6.25%)
    2 / 35 (5.71%)
         occurrences all number
    4
    2
    Musculoskeletal pain
         subjects affected / exposed
    1 / 48 (2.08%)
    3 / 35 (8.57%)
         occurrences all number
    1
    3
    Neck pain
         subjects affected / exposed
    1 / 48 (2.08%)
    3 / 35 (8.57%)
         occurrences all number
    1
    15
    Pain in extremity
         subjects affected / exposed
    2 / 48 (4.17%)
    3 / 35 (8.57%)
         occurrences all number
    2
    4
    Myalgia
         subjects affected / exposed
    1 / 48 (2.08%)
    2 / 35 (5.71%)
         occurrences all number
    1
    4
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    12 / 48 (25.00%)
    10 / 35 (28.57%)
         occurrences all number
    13
    14
    Hyperglycaemia
         subjects affected / exposed
    2 / 48 (4.17%)
    2 / 35 (5.71%)
         occurrences all number
    2
    4
    Hypomagnesaemia
         subjects affected / exposed
    3 / 48 (6.25%)
    0 / 35 (0.00%)
         occurrences all number
    3
    0
    Hyponatraemia
         subjects affected / exposed
    1 / 48 (2.08%)
    2 / 35 (5.71%)
         occurrences all number
    1
    3
    Infections and infestations
    Gingivitis
         subjects affected / exposed
    0 / 48 (0.00%)
    2 / 35 (5.71%)
         occurrences all number
    0
    3
    Influenza
         subjects affected / exposed
    3 / 48 (6.25%)
    1 / 35 (2.86%)
         occurrences all number
    3
    1
    Lower respiratory tract infection
         subjects affected / exposed
    3 / 48 (6.25%)
    0 / 35 (0.00%)
         occurrences all number
    3
    0
    Nasopharyngitis
         subjects affected / exposed
    0 / 48 (0.00%)
    2 / 35 (5.71%)
         occurrences all number
    0
    4
    Pharyngitis
         subjects affected / exposed
    0 / 48 (0.00%)
    3 / 35 (8.57%)
         occurrences all number
    0
    4
    Sinusitis
         subjects affected / exposed
    1 / 48 (2.08%)
    2 / 35 (5.71%)
         occurrences all number
    1
    2
    Rhinitis
         subjects affected / exposed
    4 / 48 (8.33%)
    2 / 35 (5.71%)
         occurrences all number
    4
    3
    Upper respiratory tract infection
         subjects affected / exposed
    3 / 48 (6.25%)
    5 / 35 (14.29%)
         occurrences all number
    3
    6
    Oral herpes
         subjects affected / exposed
    0 / 48 (0.00%)
    2 / 35 (5.71%)
         occurrences all number
    0
    3
    Viral upper respiratory tract infection
         subjects affected / exposed
    11 / 48 (22.92%)
    3 / 35 (8.57%)
         occurrences all number
    14
    4

    More information

    Close Top of page

    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    15 Dec 2015
    To add liver safety monitoring guidelines in accordance with United States Food and Drug Administration (US FDA) Guidance for Industry Drug-Induced Liver Injury: Premarketing Clinical Evaluation (2009). To update the dose modification guidelines taking into consideration the type of toxicity.

    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