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    Clinical Trial Results:
    A Phase 1, First in Human, Single-Arm, Open-Label Study Of Once a Day, Orally Administered Talazoparib (bmn 673) in Patients With Advanced or Recurrent Solid Tumors

    Summary
    EudraCT number
    2010-023062-40
    Trial protocol
    GB  
    Global end of trial date

    Results information
    Results version number
    v1(current)
    This version publication date
    15 Feb 2018
    First version publication date
    15 Feb 2018
    Other versions

    Trial information

    Close Top of page
    Trial identification
    Sponsor protocol code
    PRP-001
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT01286987
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Pfizer, Inc.
    Sponsor organisation address
    235 E 42nd Street, New York, United States, 10017
    Public contact
    Pfizer ClinicalTrials.gov Call Center, Pfizer, Inc., Pfizer ClinicalTrials.gov Call Center, 001 18007181021, ClinicalTrials.gov_Inquiries@pfizer.com
    Scientific contact
    Pfizer ClinicalTrials.gov Call Center, Pfizer ClinicalTrials.gov Call Center, 001 18007181021, 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
    Interim
    Date of interim/final analysis
    22 Aug 2016
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    31 Mar 2015
    Global end of trial reached?
    No
    General information about the trial
    Main objective of the trial
    To establish the MTD of daily, orally administered talazoparib.
    Protection of trial subjects
    This study was conducted in accordance with the US Code of Federal Regulations (CFR) sections that address clinical research studies, and/or other national and local regulations, as applicable, ICH Harmonised Tripartite Guideline: Guideline for Good Clinical Practice E6 (ICH E6) and the ethical principles established by the Declaration of Helsinki.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    11 Jan 2011
    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
    United States: 110
    Worldwide total number of subjects
    110
    EEA total number of subjects
    0
    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)
    78
    From 65 to 84 years
    31
    85 years and over
    1

    Subject disposition

    Close Top of page
    Recruitment
    Recruitment details
    -

    Pre-assignment
    Screening details
    Study was conducted in two parts: Part 1 was dose escalation phase (to determine the maximum tolerated dose [MTD]) and Part 2 was the dose expansion phase conducted at MTD determined in Part 1. Subjects were different in both of the Parts.

    Period 1
    Period 1 title
    Baseline Period
    Is this the baseline period?
    Yes
    Allocation method
    Not applicable
    Blinding used
    Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Part 1: Talazoparib 25 mcg
    Arm description
    Subjects received talazoparib capsules at a dose of 25 microgram per day (mcg/day) once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.
    Arm type
    Experimental

    Investigational medicinal product name
    Talazoparib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received talazoparib capsules at a dose of 25 mcg once daily.

    Arm title
    Part 1: Talazoparib 50 mcg
    Arm description
    Subjects received talazoparib capsules at a dose of 50 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.
    Arm type
    Experimental

    Investigational medicinal product name
    Talazoparib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received talazoparib capsules at a dose of 50 mcg once daily.

    Arm title
    Part 1: Talazoparib 100 mcg
    Arm description
    Subjects received talazoparib capsules at a dose of 100 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.
    Arm type
    Experimental

    Investigational medicinal product name
    Talazoparib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received talazoparib capsules at a dose of 100 mcg once daily.

    Arm title
    Part 1: Talazoparib 200 mcg
    Arm description
    Subjects received talazoparib capsules at a dose of 200 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.
    Arm type
    Experimental

    Investigational medicinal product name
    Talazoparib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received talazoparib capsules at a dose of 200 mcg once daily.

    Arm title
    Part 1: Talazoparib 400 mcg
    Arm description
    Subjects received talazoparib capsules at a dose of 400 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.
    Arm type
    Experimental

    Investigational medicinal product name
    Talazoparib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received talazoparib capsules at a dose of 400 mcg once daily.

    Arm title
    Part 1: Talazoparib 600 mcg
    Arm description
    Subjects received talazoparib capsules at a dose of 600 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.
    Arm type
    Experimental

    Investigational medicinal product name
    Talazoparib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received talazoparib capsules at a dose of 600 mcg once daily.

    Arm title
    Part 1: Talazoparib 900 mcg
    Arm description
    Subjects received talazoparib capsules at a dose of 900 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.
    Arm type
    Experimental

    Investigational medicinal product name
    Talazoparib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received talazoparib capsules at a dose of 900 mcg once daily.

    Arm title
    Part 1: Talazoparib 1000 mcg
    Arm description
    Subjects received talazoparib capsules at a dose of 1000 microgram per day (mcg/day) once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.
    Arm type
    Experimental

    Investigational medicinal product name
    Talazoparib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received talazoparib capsules at a dose of 1000 mcg once daily.

    Arm title
    Part 1: Talazoparib 1100 mcg
    Arm description
    Subjects received talazoparib capsules at a dose of 1100 microgram per day (mcg/day) once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.
    Arm type
    Experimental

    Investigational medicinal product name
    Talazoparib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received talazoparib capsules at a dose of 1100 mcg once daily.

    Arm title
    Part 2: Talazoparib (Breast Cancer)
    Arm description
    Subjects with breast cancer, received talazoparib capsules at the MTD as determined in Part 1 (1000 mcg/day), orally once daily in each 28-day treatment cycle (up to a maximum of 40 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.
    Arm type
    Experimental

    Investigational medicinal product name
    Talazoparib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received talazoparib capsules at a dose of 1000 mcg once daily.

    Arm title
    Part 2: Talazoparib (Ovarian/ Peritoneal Cancer)
    Arm description
    Subjects with ovarian/ peritoneal cancer, received talazoparib capsules at the MTD as determined in Part 1 (1000 mcg/day), orally once daily in each 28-day treatment cycle (up to a maximum of 40 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.
    Arm type
    Experimental

    Investigational medicinal product name
    Talazoparib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received talazoparib capsules at a dose of 1000 mcg once daily.

    Arm title
    Part 2: Talazoparib (Pancreatic Cancer)
    Arm description
    Subjects with pancreatic cancer, received talazoparib capsules at the MTD as determined in Part 1 (1000 mcg/day), orally once daily in each 28-day treatment cycle (up to a maximum of 40 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.
    Arm type
    Experimental

    Investigational medicinal product name
    Talazoparib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received talazoparib capsules at a dose of 1000 mcg once daily.

    Arm title
    Part 2: Talazoparib (Ewing Cancer)
    Arm description
    Subjects with ewing cancer, received talazoparib capsules at the MTD as determined in Part 1 (1000 mcg/day), orally once daily in each 28-day treatment cycle (up to a maximum of 40 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.
    Arm type
    Experimental

    Investigational medicinal product name
    Talazoparib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received talazoparib capsules at a dose of 1000 mcg once daily.

    Arm title
    Part 2: Talazoparib (SCLC Cancer)
    Arm description
    Subjects with SCLC cancer, received talazoparib capsules at the MTD as determined in Part 1 (1000 mcg/day), orally once daily in each 28-day treatment cycle (up to a maximum of 40 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.
    Arm type
    Experimental

    Investigational medicinal product name
    Talazoparib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received talazoparib capsules at a dose of 1000 mcg once daily.

    Arm title
    Part 2: Talazoparib (Prostate Cancer)
    Arm description
    Subjects with prostate cancer, received talazoparib capsules at the MTD as determined in Part 1 (1000 mcg/day), orally once daily in each 28-day treatment cycle (up to a maximum of 40 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.
    Arm type
    Experimental

    Investigational medicinal product name
    Talazoparib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received talazoparib capsules at a dose of 1000 mcg once daily.

    Number of subjects in period 1
    Part 1: Talazoparib 25 mcg Part 1: Talazoparib 50 mcg Part 1: Talazoparib 100 mcg Part 1: Talazoparib 200 mcg Part 1: Talazoparib 400 mcg Part 1: Talazoparib 600 mcg Part 1: Talazoparib 900 mcg Part 1: Talazoparib 1000 mcg Part 1: Talazoparib 1100 mcg Part 2: Talazoparib (Breast Cancer) Part 2: Talazoparib (Ovarian/ Peritoneal Cancer) Part 2: Talazoparib (Pancreatic Cancer) Part 2: Talazoparib (Ewing Cancer) Part 2: Talazoparib (SCLC Cancer) Part 2: Talazoparib (Prostate Cancer)
    Started
    3
    3
    3
    3
    3
    6
    6
    6
    6
    12
    11
    10
    12
    23
    3
    Completed
    3
    3
    3
    3
    3
    6
    6
    6
    6
    12
    11
    10
    12
    23
    3
    Period 2
    Period 2 title
    Part 1: Dose Escalation
    Is this the baseline period?
    No
    Allocation method
    Not applicable
    Blinding used
    Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Part 1: Talazoparib 25 mcg
    Arm description
    Subjects received talazoparib capsules at a dose of 25 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.
    Arm type
    Experimental

    Investigational medicinal product name
    Talazoparib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received talazoparib capsules at a dose of 25 mcg once daily.

    Arm title
    Part 1: Talazoparib 50 mcg
    Arm description
    Subjects received talazoparib capsules at a dose of 50 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.
    Arm type
    Experimental

    Investigational medicinal product name
    Talazoparib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received talazoparib capsules at a dose of 50 mcg once daily.

    Arm title
    Part 1: Talazoparib 100 mcg
    Arm description
    Subjects received talazoparib capsules at a dose of 100 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.
    Arm type
    Experimental

    Investigational medicinal product name
    Talazoparib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received talazoparib capsules at a dose of 100 mcg once daily.

    Arm title
    Part 1: Talazoparib 200 mcg
    Arm description
    Subjects received talazoparib capsules at a dose of 200 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.
    Arm type
    Experimental

    Investigational medicinal product name
    Talazoparib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received talazoparib capsules at a dose of 200 mcg once daily.

    Arm title
    Part 1: Talazoparib 400 mcg
    Arm description
    Subjects received talazoparib capsules at a dose of 400 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.
    Arm type
    Experimental

    Investigational medicinal product name
    Talazoparib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received talazoparib capsules at a dose of 400 mcg once daily.

    Arm title
    Part 1: Talazoparib 600 mcg
    Arm description
    Subjects received talazoparib capsules at a dose of 600 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.
    Arm type
    Experimental

    Investigational medicinal product name
    Talazoparib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received talazoparib capsules at a dose of 600 mcg once daily.

    Arm title
    Part 1: Talazoparib 900 mcg
    Arm description
    Subjects received talazoparib capsules at a dose of 900 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.
    Arm type
    Experimental

    Investigational medicinal product name
    Talazoparib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received talazoparib capsules at a dose of 900 mcg once daily.

    Arm title
    Part 1: Talazoparib 1000 mcg
    Arm description
    Subjects received talazoparib capsules at a dose of 1000 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.
    Arm type
    Experimental

    Investigational medicinal product name
    Talazoparib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received talazoparib capsules at a dose of 1000 mcg once daily.

    Arm title
    Part 1: Talazoparib 1100 mcg
    Arm description
    Subjects received talazoparib capsules at a dose of 1100 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.
    Arm type
    Experimental

    Investigational medicinal product name
    Talazoparib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received talazoparib capsules at a dose of 1100 mcg once daily.

    Number of subjects in period 2 [1]
    Part 1: Talazoparib 25 mcg Part 1: Talazoparib 50 mcg Part 1: Talazoparib 100 mcg Part 1: Talazoparib 200 mcg Part 1: Talazoparib 400 mcg Part 1: Talazoparib 600 mcg Part 1: Talazoparib 900 mcg Part 1: Talazoparib 1000 mcg Part 1: Talazoparib 1100 mcg
    Started
    3
    3
    3
    3
    3
    6
    6
    6
    6
    Colorectal Cancer
    1
    0
    1
    0
    0
    0
    0 [2]
    0 [3]
    0
    Prostate Cancer
    0
    0
    0
    0
    0
    1
    0 [4]
    0 [5]
    0
    Ewing Cancer
    0
    0
    0
    0
    0
    0
    0 [6]
    1
    1
    Pancreatic Cancer
    1
    2
    0
    0
    0
    0
    0 [7]
    0 [8]
    0
    Ovarian/ Peritoneal Cancer
    1
    1
    2
    3
    3
    4
    4
    3
    2
    Breast Cancer
    0
    0
    0
    0
    0
    1
    2
    2
    3
    Completed
    0
    0
    0
    0
    0
    0
    1
    1
    0
    Not completed
    3
    3
    3
    3
    3
    6
    5
    5
    6
         Physician decision
    -
    -
    -
    -
    1
    -
    -
    -
    -
         Progressive Disease
    2
    2
    3
    2
    1
    5
    5
    3
    5
         Clinical Progression
    1
    1
    -
    1
    1
    1
    -
    2
    1
    Notes
    [1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
    Justification: Period 1 and period 2 had different enrolled population.
    [2] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: The Milestone represents the number of subjects enrolled according to the type of cancer.
    [3] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: The Milestone represents the number of subjects enrolled according to the type of cancer.
    [4] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: The Milestone represents the number of subjects enrolled according to the type of cancer.
    [5] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: The Milestone represents the number of subjects enrolled according to the type of cancer.
    [6] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: The Milestone represents the number of subjects enrolled according to the type of cancer.
    [7] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: The Milestone represents the number of subjects enrolled according to the type of cancer.
    [8] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: The Milestone represents the number of subjects enrolled according to the type of cancer.
    Period 3
    Period 3 title
    Part 2: Dose Expansion
    Is this the baseline period?
    No
    Allocation method
    Not applicable
    Blinding used
    Not blinded

    Arms
    Are arms mutually exclusive
    No

    Arm title
    Part 2: Talazoparib (Breast Cancer)
    Arm description
    Subjects with breast cancer, received talazoparib capsules at the MTD as determined in Part 1 (1000 mcg/day), orally once daily in each 28-day treatment cycle (up to a maximum of 40 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.
    Arm type
    Experimental

    Investigational medicinal product name
    Talazoparib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received talazoparib capsules at a dose of 1000 mcg once daily.

    Arm title
    Part 2: Talazoparib (Ovarian/ Peritoneal Cancer)
    Arm description
    Subjects with ovarian/ peritoneal cancer, received talazoparib capsules at the MTD as determined in Part 1 (1000 mcg/day), orally once daily in each 28-day treatment cycle (up to a maximum of 40 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.
    Arm type
    Experimental

    Investigational medicinal product name
    Talazoparib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received talazoparib capsules at a dose of 1000 mcg once daily.

    Arm title
    Part 2: Talazoparib (Pancreatic Cancer)
    Arm description
    Subjects with pancreatic cancer, received talazoparib capsules at the MTD as determined in Part 1 (1000 mcg/day), orally once daily in each 28-day treatment cycle (up to a maximum of 40 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.
    Arm type
    Experimental

    Investigational medicinal product name
    Talazoparib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received talazoparib capsules at a dose of 1000 mcg once daily.

    Arm title
    Part 2: Talazoparib (Ewing Cancer)
    Arm description
    Subjects with ewing cancer, received talazoparib capsules at the MTD as determined in Part 1 (1000 mcg/day), orally once daily in each 28-day treatment cycle (up to a maximum of 40 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.
    Arm type
    Experimental

    Investigational medicinal product name
    Talazoparib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received talazoparib capsules at a dose of 1000 mcg once daily.

    Arm title
    Part 2: Talazoparib (SCLC Cancer)
    Arm description
    Subjects with SCLC cancer, received talazoparib capsules at the MTD as determined in Part 1 (1000 mcg/day), orally once daily in each 28-day treatment cycle (up to a maximum of 40 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.
    Arm type
    Experimental

    Investigational medicinal product name
    Talazoparib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received talazoparib capsules at a dose of 1000 mcg once daily.

    Arm title
    Part 2: Talazoparib (Prostate Cancer)
    Arm description
    Subjects with prostate cancer, received talazoparib capsules at the MTD as determined in Part 1 (1000 mcg/day), orally once daily in each 28-day treatment cycle (up to a maximum of 40 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.
    Arm type
    Experimental

    Investigational medicinal product name
    Talazoparib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received talazoparib capsules at a dose of 1000 mcg once daily.

    Number of subjects in period 3
    Part 2: Talazoparib (Breast Cancer) Part 2: Talazoparib (Ovarian/ Peritoneal Cancer) Part 2: Talazoparib (Pancreatic Cancer) Part 2: Talazoparib (Ewing Cancer) Part 2: Talazoparib (SCLC Cancer) Part 2: Talazoparib (Prostate Cancer)
    Started
    12
    11
    10
    12
    23
    3
    Completed
    1
    2
    1
    0
    0
    1
    Not completed
    11
    9
    9
    12
    23
    2
         Adverse event, serious fatal
    -
    -
    -
    1
    1
    -
         Consent withdrawn by subject
    -
    1
    -
    -
    -
    -
         Physician decision
    -
    1
    -
    -
    -
    -
         Progressive Disease
    11
    6
    7
    11
    19
    2
         Not specified
    -
    -
    -
    -
    1
    -
         Clinical Progression
    -
    1
    2
    -
    2
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Part 1: Talazoparib 25 mcg
    Reporting group description
    Subjects received talazoparib capsules at a dose of 25 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.

    Reporting group title
    Part 1: Talazoparib 50 mcg
    Reporting group description
    Subjects received talazoparib capsules at a dose of 50 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.

    Reporting group title
    Part 1: Talazoparib 100 mcg
    Reporting group description
    Subjects received talazoparib capsules at a dose of 100 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.

    Reporting group title
    Part 1: Talazoparib 200 mcg
    Reporting group description
    Subjects received talazoparib capsules at a dose of 200 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.

    Reporting group title
    Part 1: Talazoparib 400 mcg
    Reporting group description
    Subjects received talazoparib capsules at a dose of 400 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.

    Reporting group title
    Part 1: Talazoparib 600 mcg
    Reporting group description
    Subjects received talazoparib capsules at a dose of 600 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.

    Reporting group title
    Part 1: Talazoparib 900 mcg
    Reporting group description
    Subjects received talazoparib capsules at a dose of 900 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.

    Reporting group title
    Part 1: Talazoparib 1000 mcg
    Reporting group description
    Subjects received talazoparib capsules at a dose of 1000 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.

    Reporting group title
    Part 1: Talazoparib 1100 mcg
    Reporting group description
    Subjects received talazoparib capsules at a dose of 1100 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.

    Reporting group title
    Part 2: Talazoparib (Breast Cancer)
    Reporting group description
    Subjects with breast cancer, received talazoparib capsules at the MTD as determined in Part 1 (1000 mcg/day), orally once daily in each 28-day treatment cycle (up to a maximum of 40 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.

    Reporting group title
    Part 2: Talazoparib (Ovarian/ Peritoneal Cancer)
    Reporting group description
    Subjects with ovarian/ peritoneal cancer, received talazoparib capsules at the MTD as determined in Part 1 (1000 mcg/day), orally once daily in each 28-day treatment cycle (up to a maximum of 40 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.

    Reporting group title
    Part 2: Talazoparib (Pancreatic Cancer)
    Reporting group description
    Subjects with pancreatic cancer, received talazoparib capsules at the MTD as determined in Part 1 (1000 mcg/day), orally once daily in each 28-day treatment cycle (up to a maximum of 40 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.

    Reporting group title
    Part 2: Talazoparib (Ewing Cancer)
    Reporting group description
    Subjects with ewing cancer, received talazoparib capsules at the MTD as determined in Part 1 (1000 mcg/day), orally once daily in each 28-day treatment cycle (up to a maximum of 40 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.

    Reporting group title
    Part 2: Talazoparib (SCLC Cancer)
    Reporting group description
    Subjects with SCLC cancer, received talazoparib capsules at the MTD as determined in Part 1 (1000 mcg/day), orally once daily in each 28-day treatment cycle (up to a maximum of 40 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.

    Reporting group title
    Part 2: Talazoparib (Prostate Cancer)
    Reporting group description
    Subjects with prostate cancer, received talazoparib capsules at the MTD as determined in Part 1 (1000 mcg/day), orally once daily in each 28-day treatment cycle (up to a maximum of 40 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.

    Reporting group values
    Part 1: Talazoparib 25 mcg Part 1: Talazoparib 50 mcg Part 1: Talazoparib 100 mcg Part 1: Talazoparib 200 mcg Part 1: Talazoparib 400 mcg Part 1: Talazoparib 600 mcg Part 1: Talazoparib 900 mcg Part 1: Talazoparib 1000 mcg Part 1: Talazoparib 1100 mcg Part 2: Talazoparib (Breast Cancer) Part 2: Talazoparib (Ovarian/ Peritoneal Cancer) Part 2: Talazoparib (Pancreatic Cancer) Part 2: Talazoparib (Ewing Cancer) Part 2: Talazoparib (SCLC Cancer) Part 2: Talazoparib (Prostate Cancer) Total
    Number of subjects
    3 3 3 3 3 6 6 6 6 12 11 10 12 23 3 110
    Age categorical
    Units: Subjects
        In utero
    0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
        Newborns (0-27 days)
    0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
        Infants and toddlers (28 days-23 months)
    0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
        Children (2-11 years)
    0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
        Adolescents (12-17 years)
    0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
        Adults (18-64 years)
    0 2 1 3 3 3 6 5 5 11 9 5 11 11 3 78
        From 65-84 years
    3 1 2 0 0 3 0 1 1 1 2 5 1 11 0 31
        85 years and over
    0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 1
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    77.7 ( 3.51 ) 66.7 ( 9.07 ) 64.0 ( 9.64 ) 48.7 ( 11.50 ) 60.7 ( 5.77 ) 61.3 ( 19.00 ) 48.2 ( 8.66 ) 45.0 ( 18.25 ) 38.8 ( 13.73 ) 46.5 ( 11.47 ) 54.2 ( 10.93 ) 65.2 ( 7.71 ) 28.7 ( 15.18 ) 64.0 ( 10.45 ) 57.3 ( 8.14 ) -
    Sex: Female, Male
    Units: Subjects
        Male|
    1 2 0 0 0 1 0 1 1 1 0 6 6 12 3 34
        Female|
    2 1 3 3 3 5 6 5 5 11 11 4 6 11 0 76
    Race/Ethnicity, Customized
    Units: Subjects
        American Indian or Alaska Native|
    0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
        Asian|
    0 0 0 0 0 0 0 0 1 2 0 0 0 0 0 3
        Black or African American|
    0 0 0 0 0 0 0 0 1 1 0 0 1 0 0 3
        Native Hawaiian or Pacific Islander|
    0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
        White|
    3 3 3 3 3 6 5 5 4 9 11 10 10 23 3 101
        Other|
    0 0 0 0 0 0 1 1 0 0 0 0 1 0 0 3

    End points

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    End points reporting groups
    Reporting group title
    Part 1: Talazoparib 25 mcg
    Reporting group description
    Subjects received talazoparib capsules at a dose of 25 microgram per day (mcg/day) once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.

    Reporting group title
    Part 1: Talazoparib 50 mcg
    Reporting group description
    Subjects received talazoparib capsules at a dose of 50 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.

    Reporting group title
    Part 1: Talazoparib 100 mcg
    Reporting group description
    Subjects received talazoparib capsules at a dose of 100 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.

    Reporting group title
    Part 1: Talazoparib 200 mcg
    Reporting group description
    Subjects received talazoparib capsules at a dose of 200 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.

    Reporting group title
    Part 1: Talazoparib 400 mcg
    Reporting group description
    Subjects received talazoparib capsules at a dose of 400 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.

    Reporting group title
    Part 1: Talazoparib 600 mcg
    Reporting group description
    Subjects received talazoparib capsules at a dose of 600 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.

    Reporting group title
    Part 1: Talazoparib 900 mcg
    Reporting group description
    Subjects received talazoparib capsules at a dose of 900 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.

    Reporting group title
    Part 1: Talazoparib 1000 mcg
    Reporting group description
    Subjects received talazoparib capsules at a dose of 1000 microgram per day (mcg/day) once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.

    Reporting group title
    Part 1: Talazoparib 1100 mcg
    Reporting group description
    Subjects received talazoparib capsules at a dose of 1100 microgram per day (mcg/day) once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.

    Reporting group title
    Part 2: Talazoparib (Breast Cancer)
    Reporting group description
    Subjects with breast cancer, received talazoparib capsules at the MTD as determined in Part 1 (1000 mcg/day), orally once daily in each 28-day treatment cycle (up to a maximum of 40 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.

    Reporting group title
    Part 2: Talazoparib (Ovarian/ Peritoneal Cancer)
    Reporting group description
    Subjects with ovarian/ peritoneal cancer, received talazoparib capsules at the MTD as determined in Part 1 (1000 mcg/day), orally once daily in each 28-day treatment cycle (up to a maximum of 40 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.

    Reporting group title
    Part 2: Talazoparib (Pancreatic Cancer)
    Reporting group description
    Subjects with pancreatic cancer, received talazoparib capsules at the MTD as determined in Part 1 (1000 mcg/day), orally once daily in each 28-day treatment cycle (up to a maximum of 40 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.

    Reporting group title
    Part 2: Talazoparib (Ewing Cancer)
    Reporting group description
    Subjects with ewing cancer, received talazoparib capsules at the MTD as determined in Part 1 (1000 mcg/day), orally once daily in each 28-day treatment cycle (up to a maximum of 40 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.

    Reporting group title
    Part 2: Talazoparib (SCLC Cancer)
    Reporting group description
    Subjects with SCLC cancer, received talazoparib capsules at the MTD as determined in Part 1 (1000 mcg/day), orally once daily in each 28-day treatment cycle (up to a maximum of 40 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.

    Reporting group title
    Part 2: Talazoparib (Prostate Cancer)
    Reporting group description
    Subjects with prostate cancer, received talazoparib capsules at the MTD as determined in Part 1 (1000 mcg/day), orally once daily in each 28-day treatment cycle (up to a maximum of 40 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.
    Reporting group title
    Part 1: Talazoparib 25 mcg
    Reporting group description
    Subjects received talazoparib capsules at a dose of 25 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.

    Reporting group title
    Part 1: Talazoparib 50 mcg
    Reporting group description
    Subjects received talazoparib capsules at a dose of 50 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.

    Reporting group title
    Part 1: Talazoparib 100 mcg
    Reporting group description
    Subjects received talazoparib capsules at a dose of 100 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.

    Reporting group title
    Part 1: Talazoparib 200 mcg
    Reporting group description
    Subjects received talazoparib capsules at a dose of 200 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.

    Reporting group title
    Part 1: Talazoparib 400 mcg
    Reporting group description
    Subjects received talazoparib capsules at a dose of 400 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.

    Reporting group title
    Part 1: Talazoparib 600 mcg
    Reporting group description
    Subjects received talazoparib capsules at a dose of 600 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.

    Reporting group title
    Part 1: Talazoparib 900 mcg
    Reporting group description
    Subjects received talazoparib capsules at a dose of 900 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.

    Reporting group title
    Part 1: Talazoparib 1000 mcg
    Reporting group description
    Subjects received talazoparib capsules at a dose of 1000 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.

    Reporting group title
    Part 1: Talazoparib 1100 mcg
    Reporting group description
    Subjects received talazoparib capsules at a dose of 1100 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.
    Reporting group title
    Part 2: Talazoparib (Breast Cancer)
    Reporting group description
    Subjects with breast cancer, received talazoparib capsules at the MTD as determined in Part 1 (1000 mcg/day), orally once daily in each 28-day treatment cycle (up to a maximum of 40 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.

    Reporting group title
    Part 2: Talazoparib (Ovarian/ Peritoneal Cancer)
    Reporting group description
    Subjects with ovarian/ peritoneal cancer, received talazoparib capsules at the MTD as determined in Part 1 (1000 mcg/day), orally once daily in each 28-day treatment cycle (up to a maximum of 40 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.

    Reporting group title
    Part 2: Talazoparib (Pancreatic Cancer)
    Reporting group description
    Subjects with pancreatic cancer, received talazoparib capsules at the MTD as determined in Part 1 (1000 mcg/day), orally once daily in each 28-day treatment cycle (up to a maximum of 40 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.

    Reporting group title
    Part 2: Talazoparib (Ewing Cancer)
    Reporting group description
    Subjects with ewing cancer, received talazoparib capsules at the MTD as determined in Part 1 (1000 mcg/day), orally once daily in each 28-day treatment cycle (up to a maximum of 40 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.

    Reporting group title
    Part 2: Talazoparib (SCLC Cancer)
    Reporting group description
    Subjects with SCLC cancer, received talazoparib capsules at the MTD as determined in Part 1 (1000 mcg/day), orally once daily in each 28-day treatment cycle (up to a maximum of 40 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.

    Reporting group title
    Part 2: Talazoparib (Prostate Cancer)
    Reporting group description
    Subjects with prostate cancer, received talazoparib capsules at the MTD as determined in Part 1 (1000 mcg/day), orally once daily in each 28-day treatment cycle (up to a maximum of 40 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.

    Subject analysis set title
    Part 1 and Part 2: Talazoparib (Breast Cancer)
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Subjects with breast cancer who received talazoparib capsules in Part 1 and 2 at a dose of either 600 mcg/day, 900 mcg/day, 1000 mcg/day, 1100 mcg/day.

    Subject analysis set title
    Part 1 and Part 2: Talazoparib (Ovarian/ Peritoneal Cancer)
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Subjects with ovarian/ peritoneal cancer who received talazoparib capsules in Part 1 and 2 at a dose of either 25 mcg/day, 50 mcg/day, 100 mcg/day, 200 mcg/day, 400 mcg/day, 600 mcg/day, 900 mcg/day, 1000 mcg/day, 1100 mcg/day.

    Subject analysis set title
    Part 1 and Part 2: Talazoparib (Pancreatic Cancer)
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Subjects with pancreatic cancer who received talazoparib capsules in Part 1 and 2 at a dose of either 25 mcg/day, 50 mcg/day, 1000 mcg/day.

    Subject analysis set title
    Part 1 and Part 2: Talazoparib (Ewing Cancer)
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Subjects with ewing cancer who received talazoparib capsules in Part 1 and 2 at a dose of either 1000 mcg/day, 1100 mcg/day.

    Subject analysis set title
    Part 2: Talazoparib (SCLC Cancer)
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Subjects with small cell lung cancer (SCLC) cancer who received talazoparib capsules in Part 2 at a dose of 1000 mcg/day.

    Subject analysis set title
    Part 1 and Part 2: Talazoparib (Prostate Cancer)
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Subjects with prostate cancer who received talazoparib capsules in Part 1 and 2 at a dose of 600 mcg/day.

    Subject analysis set title
    Part 1: Talazoparib (Colorectal Cancer)
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Subjects with colorectal cancer who received talazoparib capsules in Part 1 at a dose of either 25 mcg/day or 100 mcg/day.

    Subject analysis set title
    Part 2: Talazoparib (SCLC Cancer)
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Subjects with SCLC cancer who received talazoparib capsules in Part 2 at a dose of 1000 mcg/day.

    Subject analysis set title
    Part 1 and Part 2: Talazoparib (Ovarian/ Peritoneal Cancer)
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Subjects with ovarian/ peritoneal cancer who received talazoparib capsules in Part 1 and 2 at a dose of either 25 mcg/day, 50 mcg/day, 100 mcg/day, 200 mcg/day, 400 mcg/day, 600 mcg/day, 900 mcg/day, 1000 mcg/day, 1100 mcg/day.

    Subject analysis set title
    Part 1 and Part 2: Talazoparib (Prostate Cancer)
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Subjects with prostate cancer who received talazoparib capsules in Part 1 and 2 at a dose of 600 mcg/day.

    Subject analysis set title
    Part 1 and Part 2: Talazoparib (Breast Cancer)
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Subjects with breast cancer who received talazoparib capsules in Part 1 and 2 at a dose of either 600 mcg/day,900 mcg/day,1000 mcg/day,1100 mcg/day.

    Subject analysis set title
    Part 1 and Part 2: Talazoparib (Ovarian/ Peritoneal Cancer)
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Subjects with ovarian/ peritoneal cancer who received talazoparib capsules in Part 1 and 2 at a dose of either 25 mcg/day, 50 mcg/day, 100 mcg/day, 200 mcg/day, 400 mcg/day, 600 mcg/day, 900 mcg/day, 1000 mcg/day, 1100 mcg/day.

    Subject analysis set title
    Part 1 and Part 2: Talazoparib (Ewing Cancer)
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Subjects with Ewing cancer who received talazoparib capsules in Part 1 and 2 at a dose of 1000 mcg/day.

    Subject analysis set title
    Part 1: Talazoparib: All Subjects
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    All subjects who received talazoparib capsules at a dose of either 25 mcg/day, 50 mcg/day, 100 mcg/day, 200 mcg/day, 400 mcg/day, 600 mcg/day, 900 mcg/day, 1000 mcg/day and 1100 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met in Part 1.

    Subject analysis set title
    Part 2: Talazoparib 1000 mcg
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    All subjects with either breast, ovarian/peritoneal, pancreatic, ewing, SCLC, or prostate cancer who received talazoparib capsules at a dose of 1000 mcg/day in Part 2.

    Subject analysis set title
    Part 1: Talazoparib 1100 mcg
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Subjects received talazoparib capsules at a dose of 1100 microgram per day (mcg/day) once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.

    Primary: Number of Subjects With Objective Response

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    End point title
    Number of Subjects With Objective Response [1]
    End point description
    Objective response: number of subjects with complete response (CR) or partial response (PR) after treatment with talazoparib and maintained for at least 4 weeks (28 days) as assessed by response evaluation criteria in solid tumors (RECIST) version 1.1. CR: disappearance of all non-nodal target lesions (where all target lesions were recorded with a length of 0 millimeter [mm] on the case report form [CRF]) and the reduction of the shortest diameter of all nodal lesions to less than [<] 10 mm. PR: 30% or more decrease in the sum of the longest diameters (SLD) + sum of shortest diameters (SSD) of target lesions, with reference to the baseline SLD+SSD. Response analysis population: all enrolled subjects who received at least 1 dose of talazoparib and had measurable disease at baseline. Data for this endpoint was planned to be analyzed combined for Part 1 and Part 2 on the basis of cancer type (pre-specified in protocol).
    End point type
    Primary
    End point timeframe
    From Baseline until disease progression or death due to any cause (maximum duration: 1071 days for Part 1; 834 days for Part 2)
    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 analysed for this endpoint.
    End point values
    Part 1 and Part 2: Talazoparib (Breast Cancer) Part 1 and Part 2: Talazoparib (Ovarian/ Peritoneal Cancer) Part 1 and Part 2: Talazoparib (Pancreatic Cancer) Part 1 and Part 2: Talazoparib (Ewing Cancer) Part 2: Talazoparib (SCLC Cancer) Part 1 and Part 2: Talazoparib (Prostate Cancer) Part 1: Talazoparib (Colorectal Cancer)
    Number of subjects analysed
    20
    31
    13
    14
    23
    1
    2
    Units: subjects
    8
    12
    2
    0
    2
    0
    0
    No statistical analyses for this end point

    Primary: Number of Subjects With Best Overall Response

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    End point title
    Number of Subjects With Best Overall Response [2]
    End point description
    Best overall response: best response (in the order of confirmed CR, confirmed PR, stable disease[SD] and progressive disease[PD]) among all overall response as RECIST 1.1, recorded from date of first dose of talazoparib until subject withdrew from study/data cut-off date. CR: disappearance of all non-nodal target lesions and the reduction of the shortest diameter of all nodal lesions to < 10 mm. PR: at least a 30% decrease in sum of the diameters of target lesions, reference to baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters on study. PD:at least a 20% increase in sum of diameters of target lesions, reference to the smallest sum on study. Response analysis population. Data for this endpoint was planned to be analyzed combined for Part 1 and Part 2 on the basis of cancer type and not planned to be analyzed for “Part 1: Colorectal Cancer” arm (pre-specified in protocol).
    End point type
    Primary
    End point timeframe
    From Baseline until disease progression or death due to any cause (maximum duration: 1071 days for Part 1; 834 days for Part 2)
    Notes
    [2] - 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 analysed for this endpoint.
    End point values
    Part 1 and Part 2: Talazoparib (Breast Cancer) Part 1 and Part 2: Talazoparib (Ovarian/ Peritoneal Cancer) Part 1 and Part 2: Talazoparib (Pancreatic Cancer) Part 1 and Part 2: Talazoparib (Ewing Cancer) Part 2: Talazoparib (SCLC Cancer) Part 1 and Part 2: Talazoparib (Prostate Cancer)
    Number of subjects analysed
    20
    31
    13
    14
    23
    1
    Units: subjects
        Complete Response (CR)|
    1
    1
    0
    0
    0
    0
        Partial Response (PR)|
    7
    11
    2
    0
    2
    0
        Stable Disease (SD)|
    7
    10
    2
    4
    4
    1
        Progressive Disease (PD)|
    5
    6
    6
    9
    14
    0
    No statistical analyses for this end point

    Primary: Progression-Free Survival (PFS)

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    End point title
    Progression-Free Survival (PFS) [3]
    End point description
    PFS was defined as the time (in weeks) from the date of first dose of study drug to the earlier date of the documented PD or death due to any cause. PD as per RECIST 1.1 defined as at least a 20% increase in the sum of diameters of target lesions, reference to the smallest sum on study (this includes the baseline sum if that was the smallest on study). Full analysis set (FAS) included all enrolled subjects who received at least 1 dose of talazoparib. Data for this endpoint was planned to be analyzed combined for Part 1 and Part 2 on the basis of cancer type and was not planned to be analyzed for “Part 1: Colorectal Cancer” arm, as pre-specified in protocol.
    End point type
    Primary
    End point timeframe
    Baseline, until PD or death due to any cause (maximum duration:1071 days for Part 1; 834 days for Part 2)
    Notes
    [3] - 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 analysed for this endpoint.
    End point values
    Part 1 and Part 2: Talazoparib (Breast Cancer) Part 1 and Part 2: Talazoparib (Pancreatic Cancer) Part 1 and Part 2: Talazoparib (Ewing Cancer) Part 2: Talazoparib (SCLC Cancer) Part 1 and Part 2: Talazoparib (Ovarian/ Peritoneal Cancer) Part 1 and Part 2: Talazoparib (Prostate Cancer)
    Number of subjects analysed
    20
    13
    14
    23
    34
    4
    Units: weeks
        median (confidence interval 95%)
    29.3 (12.1 to 43.4)
    5.3 (2.4 to 21.3)
    6.2 (3.1 to 14.0)
    11.1 (4.3 to 13.0)
    32.1 (18.9 to 38.6)
    12.1 (12.0 to 99999)
    No statistical analyses for this end point

    Primary: Duration of Response

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    End point title
    Duration of Response [4]
    End point description
    Duration of response was defined as the time (in weeks) from the date of the first documented objective response confirmed at least 28 days later to the date of the first documented PD or date of death, whichever occurred first. PD as per RECIST v1.1 defined as at least a 20% increase in the sum of diameters of target lesions, reference to the smallest sum on study (this includes the baseline sum if that was the smallest on study). Analysis was performed on the subset of response analysis population which included all subjects who had response. Data for this endpoint was planned to be analyzed combined for Part 1 and Part 2 on the basis of cancer type and was not planned to be analyzed for “Part 1: Colorectal Cancer” arm, as pre-specified in protocol.
    End point type
    Primary
    End point timeframe
    Baseline until PD or death due to any cause (maximum duration: 1071 days for Part 1; 834 days for Part 2)
    Notes
    [4] - 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 analysed for this endpoint.
    End point values
    Part 1 and Part 2: Talazoparib (Breast Cancer) Part 1 and Part 2: Talazoparib (Ovarian/ Peritoneal Cancer) Part 1 and Part 2: Talazoparib (Pancreatic Cancer) Part 1 and Part 2: Talazoparib (Ewing Cancer) Part 2: Talazoparib (SCLC Cancer) Part 1 and Part 2: Talazoparib (Prostate Cancer) Part 1: Talazoparib (Colorectal Cancer)
    Number of subjects analysed
    8
    12
    2
    0 [5]
    2
    0 [6]
    0 [7]
    Units: weeks
        median (confidence interval 95%)
    32.2 (20.1 to 64.1)
    26.9 (15.7 to 35.1)
    99999 (21.6 to 99999)
    ( to )
    13.6 (12.0 to 15.3)
    ( to )
    ( to )
    Notes
    [5] - None of the subjects had confirmed CR or PR, hence duration of response was not analyzed.
    [6] - None of the subjects had confirmed CR or PR, hence duration of response was not analyzed.
    [7] - None of the subjects had confirmed CR or PR, hence duration of response was not analyzed.
    No statistical analyses for this end point

    Primary: Number of Subjects With Stable Disease

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    End point title
    Number of Subjects With Stable Disease [8]
    End point description
    SD defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. PD defined as at least a 20% increase in sum of diameters of target lesions, reference to the smallest sum on study (this includes the baseline sum if that was the smallest on study). Response analysis population included all enrolled subjects who received at least 1 dose of talazoparib, and had measurable disease at baseline. Data for this endpoint was planned to be analyzed combined for Part 1 and Part 2 on the basis of cancer type and was not planned to be analyzed for “Part 1: Colorectal Cancer” arm, as pre-specified in protocol.
    End point type
    Primary
    End point timeframe
    Baseline, until PD or death due to any cause (maximum duration: 1071 days for Part 1; 834 days for Part 2)
    Notes
    [8] - 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 analysed for this endpoint.
    End point values
    Part 1 and Part 2: Talazoparib (Breast Cancer) Part 1 and Part 2: Talazoparib (Ovarian/ Peritoneal Cancer) Part 1 and Part 2: Talazoparib (Pancreatic Cancer) Part 1 and Part 2: Talazoparib (Ewing Cancer) Part 2: Talazoparib (SCLC Cancer) Part 1 and Part 2: Talazoparib (Prostate Cancer)
    Number of subjects analysed
    20
    31
    13
    14
    23
    1
    Units: subjects
    7
    10
    2
    4
    4
    1
    No statistical analyses for this end point

    Primary: Part 1: Maximum Tolerated Dose (MTD) 

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    End point title
    Part 1: Maximum Tolerated Dose (MTD)  [9]
    End point description
    MTD: the highest dose at which no more than 1 of 6 subjects experienced a Dose Limiting Toxicity (DLT). DLT: any of the following occurring during Cycle 1 of Part 1 of study, Hematologic toxicity: Any grade 4 or higher hematologic adverse event, Grade 3 thrombocytopenia associated with grade 2 or higher haemorrhage, Grade 3 thrombocytopenia or neutropenia that led to interruption of dosing for 5 or more days. Nonhematologic toxicity: grade 3 or higher laboratory AE which was asymptomatic and rapidly reversible AEs (returned to baseline or grade 1 within 7 days), Grade 3 nausea, vomiting, or diarrhea that could be medically managed to grade 2 or lower with anti-emetics and/or anti-diarrheals within 24 hours, Grade 3 fatigue improved to grade 2 or lower in 5 days or less, Alopecia. Grades based on National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03. Safety analysis set included all enrolled subjects who received at least 1 dose of talazoparib.
    End point type
    Primary
    End point timeframe
    Cycle 1 (Day 1 up to Day 42)
    Notes
    [9] - 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 analysed for this endpoint.
    End point values
    Part 1: Talazoparib: All Subjects
    Number of subjects analysed
    39
    Units: mcg/day
    1000
    No statistical analyses for this end point

    Primary: Part 1: Recommended Part 2 Dose of Talazoparib

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    End point title
    Part 1: Recommended Part 2 Dose of Talazoparib [10]
    End point description
    The Recommended dose of talazoparib for use in Part 2 was determined in Part 1 (dose escalation) on the basis of the totality of safety, pharmacokinetics (PK), pharmacodynamic and preliminary efficacy data observed in Cycles 1 and 2 and beyond. Safety analysis set included all enrolled subjects who received at least 1 dose of talazoparib.
    End point type
    Primary
    End point timeframe
    Baseline up to Cycle 50 (each Cycle 28 days)
    Notes
    [10] - 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 analysed for this endpoint.
    End point values
    Part 1: Talazoparib: All Subjects
    Number of subjects analysed
    39
    Units: mcg/day
    1000
    No statistical analyses for this end point

    Other pre-specified: Part 1 and 2: Number of Subjects With Treatment-Emergent Adverse events and Serious Adverse Events

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    End point title
    Part 1 and 2: Number of Subjects With Treatment-Emergent Adverse events and Serious Adverse Events
    End point description
    An AE was any untoward medical occurrence in a subject who received study drug without regard to possibility of causal relationship. An 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. Treatment-emergent were events between first dose of study drug and up to end of study (up to 1071 days for Part 1 and up to 834 days for Part 2) that were absent before treatment or that worsened relative to pre-treatment state. Safety analyses set included all enrolled subjects who received at least 1 dose of talazoparib.
    End point type
    Other pre-specified
    End point timeframe
    Part 1: Baseline up to 1071 days; Part 2: Baseline up to 834 days
    End point values
    Part 1: Talazoparib 25 mcg Part 2: Talazoparib (Breast Cancer) Part 1: Talazoparib 50 mcg Part 2: Talazoparib (Ovarian/ Peritoneal Cancer) Part 1: Talazoparib 100 mcg Part 2: Talazoparib (Pancreatic Cancer) Part 1: Talazoparib 200 mcg Part 2: Talazoparib (Ewing Cancer) Part 1: Talazoparib 400 mcg Part 2: Talazoparib (SCLC Cancer) Part 1: Talazoparib 600 mcg Part 2: Talazoparib (Prostate Cancer) Part 1: Talazoparib 900 mcg Part 1: Talazoparib 1000 mcg Part 1: Talazoparib 1100 mcg
    Number of subjects analysed
    3
    12
    3
    11
    3
    10
    3
    12
    3
    23
    6
    3
    6
    6
    6
    Units: subjects
        AEs
    2
    12
    3
    11
    2
    10
    3
    12
    3
    21
    6
    2
    6
    6
    6
        SAEs
    1
    2
    2
    5
    2
    6
    3
    4
    0
    8
    2
    0
    3
    1
    3
    No statistical analyses for this end point

    Other pre-specified: Part 1: Maximum Observed Plasma Concentration (Cmax) of Talazoparib

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    End point title
    Part 1: Maximum Observed Plasma Concentration (Cmax) of Talazoparib
    End point description
    The pharmacokinetic (PK) evaluable population included all subjects who received at least 1 dose of talazoparib with adequate PK results to perform PK calculations and was used for analysis of PK endpoints.
    End point type
    Other pre-specified
    End point timeframe
    Cycle 1: 0.25, 0.5, 0.75, 1, 2, 3, 4, 5, 6, 8, 10, 24, 48, 72 and 96 hours postdose on Day 1 and Day 35
    End point values
    Part 1: Talazoparib 25 mcg Part 1: Talazoparib 50 mcg Part 1: Talazoparib 100 mcg Part 1: Talazoparib 200 mcg Part 1: Talazoparib 400 mcg Part 1: Talazoparib 600 mcg Part 1: Talazoparib 900 mcg Part 1: Talazoparib 1000 mcg Part 1: Talazoparib 1100 mcg
    Number of subjects analysed
    3
    3
    3
    3
    3
    6
    6
    6
    6
    Units: picograms per milliliter (pg/mL)
    arithmetic mean (standard deviation)
        Cycle 1 Day 1|
    60.0 ( 15.9 )
    79.7 ( 7.50 )
    214 ( 50.9 )
    788 ( 369 )
    1830 ( 699 )
    4100 ( 1400 )
    6100 ( 3060 )
    10600 ( 4220 )
    13200 ( 3220 )
        Cycle 1 Day 35|
    300 ( 78.8 )
    615 ( 74.2 )
    1880 ( 332 )
    5620 ( 3530 )
    6560 ( 1500 )
    11300 ( 3230 )
    15400 ( 1540 )
    21000 ( 7990 )
    23400 ( 4810 )
    No statistical analyses for this end point

    Other pre-specified: Part 2: Maximum Observed Plasma Concentration (Cmax) of Talazoparib

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    End point title
    Part 2: Maximum Observed Plasma Concentration (Cmax) of Talazoparib
    End point description
    The PK evaluable population included all subjects who received at least 1 dose of talazoparib with adequate PK results to perform PK calculations and was used for analysis of PK endpoints. PK data was planned to be reported for the overall subjects in Part 2, as pre-specified in protocol.
    End point type
    Other pre-specified
    End point timeframe
    Cycle 1 and 2: Predose, 0.5, 1, 2, 3 and 4 hours postdose on Day 1
    End point values
    Part 2: Talazoparib 1000 mcg
    Number of subjects analysed
    70
    Units: pg/mL
    arithmetic mean (standard deviation)
        Cycle 1 Day 1|
    8480 ( 3890 )
        Cycle 2 Day 1|
    17700 ( 5790 )
    No statistical analyses for this end point

    Other pre-specified: Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Talazoparib

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    End point title
    Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Talazoparib
    End point description
    The PK evaluable population included all subjects who received at least 1 dose of talazoparib with adequate PK results to perform PK calculations and was used for analysis of PK endpoints.
    End point type
    Other pre-specified
    End point timeframe
    Cycle 1: 0.25, 0.5, 0.75, 1, 2, 3, 4, 5, 6, 8, 10, 24, 48, 72 and 96 hours postdose on Day 1 and Day 35
    End point values
    Part 1: Talazoparib 25 mcg Part 1: Talazoparib 50 mcg Part 1: Talazoparib 100 mcg Part 1: Talazoparib 200 mcg Part 1: Talazoparib 400 mcg Part 1: Talazoparib 600 mcg Part 1: Talazoparib 900 mcg Part 1: Talazoparib 1000 mcg Part 1: Talazoparib 1100 mcg
    Number of subjects analysed
    3
    3
    3
    3
    3
    6
    6
    6
    6
    Units: hours
    median (full range (min-max))
        Cycle 1 Day 1|
    7.92 (1.95 to 9.95)
    1.00 (0.800 to 1.02)
    1.02 (1.00 to 3.98)
    1.03 (1.00 to 2.32)
    2.03 (0.750 to 2.95)
    0.835 (0.750 to 1.95)
    2.00 (1.02 to 9.98)
    1.03 (0.730 to 2.07)
    1.00 (0.730 to 2.05)
        Cycle 1 Day 35|
    1.02 (0.580 to 3.98)
    5.43 (0.770 to 10.1)
    0.785 (0.750 to 0.820)
    1.97 (1.00 to 3.02)
    0.980 (0.750 to 2.00)
    1.04 (0.730 to 5.98)
    1.02 (0.970 to 2.07)
    1.02 (0.750 to 2.00)
    1.48 (0.980 to 2.00)
    No statistical analyses for this end point

    Other pre-specified: Part 2: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Talazoparib

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    End point title
    Part 2: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Talazoparib
    End point description
    The PK evaluable population included all subjects who received at least 1 dose of talazoparib with adequate PK results to perform PK calculations and was used for analysis of PK endpoints. PK data was planned to be reported for the overall subjects in Part 2, as pre-specified in protocol.
    End point type
    Other pre-specified
    End point timeframe
    Cycle 1 and 2: Predose, 0.5, 1, 2, 3 and 4 hours postdose on Day 1
    End point values
    Part 2: Talazoparib 1000 mcg
    Number of subjects analysed
    70
    Units: hours
    median (full range (min-max))
        Cycle 1 Day 1|
    1.00 (0.500 to 4.07)
        Cycle 2 Day 1|
    1.07 (0.500 to 6.05)
    No statistical analyses for this end point

    Other pre-specified: Part 1: Area Under the Plasma Concentration-Time Curve (AUC) From Time 0 to the Time of the Last Measurable Concentration (AUC0-last) of Talazoparib

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    End point title
    Part 1: Area Under the Plasma Concentration-Time Curve (AUC) From Time 0 to the Time of the Last Measurable Concentration (AUC0-last) of Talazoparib
    End point description
    Area under the plasma concentration time-curve from zero to the time of last measured concentration (AUC0-last). The PK evaluable population included all subjects who received at least 1 dose of talazoparib with adequate PK results to perform PK calculations and was used for analysis of PK endpoints. Data for this endpoint was analyzed on Cycle 1 Day 1.
    End point type
    Other pre-specified
    End point timeframe
    Cycle 1: 0.25, 0.5, 0.75, 1, 2, 3, 4, 5, 6, 8, 10, 24, 48, 72 and 96 hours postdose on Day 1
    End point values
    Part 1: Talazoparib 25 mcg Part 1: Talazoparib 50 mcg Part 1: Talazoparib 100 mcg Part 1: Talazoparib 200 mcg Part 1: Talazoparib 400 mcg Part 1: Talazoparib 600 mcg Part 1: Talazoparib 900 mcg Part 1: Talazoparib 1000 mcg Part 1: Talazoparib 1100 mcg
    Number of subjects analysed
    3
    3
    3
    3
    3
    6
    6
    6
    6
    Units: pg*hr/mL
        arithmetic mean (standard deviation)
    3600 ( 1360 )
    5340 ( 1960 )
    16600 ( 5320 )
    39300 ( 11700 )
    43700 ( 15000 )
    97900 ( 30000 )
    160000 ( 66100 )
    182000 ( 62400 )
    201000 ( 93400 )
    No statistical analyses for this end point

    Other pre-specified: Part 2: Area Under the Plasma Concentration-Time Curve (AUC) From Time 0 to the Time of the Last Measurable Concentration (AUC0-last) of Talazoparib

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    End point title
    Part 2: Area Under the Plasma Concentration-Time Curve (AUC) From Time 0 to the Time of the Last Measurable Concentration (AUC0-last) of Talazoparib
    End point description
    Area under the plasma concentration time-curve from zero to the time of last measured concentration (AUC0-last). The PK evaluable population included all subjects who received at least 1 dose of talazoparib with adequate PK results to perform PK calculations and was used for analysis of PK endpoints. PK data was planned to be reported for the overall subjects in Part 2, as pre-specified in protocol.
    End point type
    Other pre-specified
    End point timeframe
    Cycle 1 and 2: Predose, 0.5, 1, 2, 3 and 4 hours postdose on Day 1
    End point values
    Part 2: Talazoparib 1000 mcg
    Number of subjects analysed
    70
    Units: pg*hr/mL
    arithmetic mean (standard deviation)
        Cycle 1 Day 1|
    19100 ( 8850 )
        Cycle 2 Day 1|
    50200 ( 16300 )
    No statistical analyses for this end point

    Other pre-specified: Part 1: Minimum Observed Plasma Concentration (Cmin) of Talazoparib

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    End point title
    Part 1: Minimum Observed Plasma Concentration (Cmin) of Talazoparib
    End point description
    The PK evaluable population included all subjects who received at least 1 dose of talazoparib with adequate PK results to perform PK calculations and was used for analysis of PK endpoints. Data for this endpoint was not planned to be analyzed for Part 2, as pre-specified in protocol.
    End point type
    Other pre-specified
    End point timeframe
    Cycle 1: 0.25, 0.5, 0.75, 1, 2, 3, 4, 5, 6, 8, 10, 24, 48, 72 and 96 hours postdose on Day 35
    End point values
    Part 1: Talazoparib 25 mcg Part 1: Talazoparib 50 mcg Part 1: Talazoparib 100 mcg Part 1: Talazoparib 200 mcg Part 1: Talazoparib 400 mcg Part 1: Talazoparib 600 mcg Part 1: Talazoparib 900 mcg Part 1: Talazoparib 1000 mcg Part 1: Talazoparib 1100 mcg
    Number of subjects analysed
    3
    3
    3
    3
    3
    6
    6
    6
    4
    Units: pg/mL
        arithmetic mean (standard deviation)
    169 ( 58.0 )
    299 ( 133 )
    1020 ( 107 )
    2880 ( 1710 )
    2230 ( 957 )
    3470 ( 1050 )
    3180 ( 802 )
    3720 ( 1590 )
    2910 ( 803 )
    No statistical analyses for this end point

    Other pre-specified: Part 1: Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0-inf)] of Talazoparib

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    End point title
    Part 1: Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0-inf)] of Talazoparib
    End point description
    AUC (0-inf) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time. The PK evaluable population included all subjects who received at least 1 dose of talazoparib with adequate PK results to perform PK calculations and was used for analysis of PK endpoints. Data for this endpoint was not planned to be analyzed for Part 2, as pre-specified in protocol.
    End point type
    Other pre-specified
    End point timeframe
    Cycle 1: 0.25, 0.5, 0.75, 1, 2, 3, 4, 5, 6, 8, 10, 24, 48, 72 and 96 hours postdose on Day 1
    End point values
    Part 1: Talazoparib 25 mcg Part 1: Talazoparib 50 mcg Part 1: Talazoparib 100 mcg Part 1: Talazoparib 200 mcg Part 1: Talazoparib 400 mcg Part 1: Talazoparib 600 mcg Part 1: Talazoparib 900 mcg Part 1: Talazoparib 1000 mcg Part 1: Talazoparib 1100 mcg
    Number of subjects analysed
    3
    3
    3
    3
    3
    6
    6
    6
    6
    Units: pg*hr/mL
        arithmetic mean (standard deviation)
    5330 ( 1840 )
    8320 ( 1960 )
    37600 ( 6620 )
    92700 ( 48500 )
    60100 ( 15900 )
    120000 ( 26000 )
    188000 ( 85700 )
    200000 ( 64000 )
    235000 ( 111000 )
    No statistical analyses for this end point

    Other pre-specified: Part 1: Terminal Half-Life (t1/2) of Talazoparib

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    End point title
    Part 1: Terminal Half-Life (t1/2) of Talazoparib
    End point description
    T1/2 is the time measured for the plasma concentration of talazoparib to decrease by one half. The PK evaluable population included all subjects who received at least 1 dose of talazoparib with adequate PK results to perform PK calculations and was used for analysis of PK endpoints. Data for this endpoint was not planned to be analyzed for Part 2, as pre-specified in protocol.
    End point type
    Other pre-specified
    End point timeframe
    Cycle 1: 0.25, 0.5, 0.75, 1, 2, 3, 4, 5, 6, 8, 10, 24, 48, 72 and 96 hours postdose on Day 1 and Day 35
    End point values
    Part 1: Talazoparib 25 mcg Part 1: Talazoparib 50 mcg Part 1: Talazoparib 100 mcg Part 1: Talazoparib 200 mcg Part 1: Talazoparib 400 mcg Part 1: Talazoparib 600 mcg Part 1: Talazoparib 900 mcg Part 1: Talazoparib 1000 mcg Part 1: Talazoparib 1100 mcg
    Number of subjects analysed
    3
    3
    3
    3
    3
    6
    6
    6
    6
    Units: Hours
    arithmetic mean (standard deviation)
        Cycle 1 Day 1|
    100 ( 11.9 )
    129 ( 42.6 )
    229 ( 158 )
    212 ( 126 )
    102 ( 27.2 )
    58.6 ( 17.3 )
    60.4 ( 10.9 )
    52.9 ( 13.4 )
    71.0 ( 20.6 )
        Cycle 1 Day 35|
    107 ( 84.2 )
    132 ( 12.3 )
    98.2 ( 4.83 )
    50.9 ( 19.1 )
    90.7 ( 32.7 )
    63.7 ( 12.7 )
    71.0 ( 14.5 )
    50.0 ( 16.6 )
    52.8 ( 23.2 )
    No statistical analyses for this end point

    Other pre-specified: Part 1: Apparent Oral Clearance (CL/F) of Talazoparib

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    End point title
    Part 1: Apparent Oral Clearance (CL/F) of Talazoparib
    End point description
    Clearance of a drug was a measure of the rate at which a drug was metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) was influenced by the fraction of the dose absorbed. The PK evaluable population included all subjects who received at least 1 dose of talazoparib with adequate PK results to perform PK calculations and was used for analysis of PK endpoints. Data for this endpoint was not planned to be analyzed for Part 2, as pre-specified in protocol.
    End point type
    Other pre-specified
    End point timeframe
    Cycle 1: 0.25, 0.5, 0.75, 1, 2, 3, 4, 5, 6, 8, 10, 24, 48, 72 and 96 hours postdose on Day 1
    End point values
    Part 1: Talazoparib 25 mcg Part 1: Talazoparib 50 mcg Part 1: Talazoparib 100 mcg Part 1: Talazoparib 200 mcg Part 1: Talazoparib 400 mcg Part 1: Talazoparib 600 mcg Part 1: Talazoparib 900 mcg Part 1: Talazoparib 1000 mcg Part 1: Talazoparib 1100 mcg
    Number of subjects analysed
    3
    3
    3
    3
    3
    6
    6
    6
    6
    Units: liter/hour
        arithmetic mean (standard deviation)
    5.17 ( 2.10 )
    6.27 ( 1.66 )
    2.72 ( 0.532 )
    2.61 ( 1.35 )
    6.95 ( 1.71 )
    5.19 ( 0.990 )
    5.49 ( 2.08 )
    5.39 ( 1.59 )
    5.32 ( 1.64 )
    No statistical analyses for this end point

    Other pre-specified: Part 1: Apparent Volume of Distribution (Vz/F) of Talazoparib

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    End point title
    Part 1: Apparent Volume of Distribution (Vz/F) of Talazoparib
    End point description
    Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Vz/F was influenced by the fraction absorbed. The PK evaluable population included all subjects who received at least 1 dose of talazoparib with adequate PK results to perform PK calculations and was used for analysis of PK endpoints. Data for this endpoint was not planned to be analyzed for Part 2, as pre-specified in protocol.
    End point type
    Other pre-specified
    End point timeframe
    Cycle 1: 0.25, 0.5, 0.75, 1, 2, 3, 4, 5, 6, 8, 10, 24, 48, 72 and 96 hours postdose on Day 1 and Day 35
    End point values
    Part 1: Talazoparib 25 mcg Part 1: Talazoparib 50 mcg Part 1: Talazoparib 100 mcg Part 1: Talazoparib 200 mcg Part 1: Talazoparib 400 mcg Part 1: Talazoparib 600 mcg Part 1: Talazoparib 900 mcg Part 1: Talazoparib 1000 mcg Part 1: Talazoparib 1100 mcg
    Number of subjects analysed
    3
    3
    3
    3
    3
    6
    6
    6
    6
    Units: liter
    arithmetic mean (standard deviation)
        Cycle 1 Day 1|
    756 ( 351 )
    1240 ( 742 )
    839 ( 487 )
    678 ( 217 )
    1050 ( 431 )
    441 ( 143 )
    468 ( 169 )
    415 ( 170 )
    549 ( 232 )
        Cycle 1 Day 35|
    1070 ( 971 )
    1020 ( 345 )
    475 ( 47.8 )
    264 ( 249 )
    818 ( 326 )
    477 ( 136 )
    604 ( 169 )
    373 ( 144 )
    472 ( 254 )
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Baseline up to end of study (maximum duration: 1071 days for Part 1; 834 days for Part 2)
    Adverse event reporting additional description
    The 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.
    Assessment type
    Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    20.0
    Reporting groups
    Reporting group title
    Part 1: Talazoparib 25 mcg
    Reporting group description
    Subjects received talazoparib capsules at a dose of 25 microgram per day (mcg/day) once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.

    Reporting group title
    Part 1: Talazoparib 50 mcg
    Reporting group description
    Subjects received talazoparib capsules at a dose of 50 microgram per day (mcg/day) once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.

    Reporting group title
    Part 1: Talazoparib 100 mcg
    Reporting group description
    Subjects received talazoparib capsules at a dose of 100 microgram per day (mcg/day) once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.

    Reporting group title
    Part 1: Talazoparib 200 mcg
    Reporting group description
    Subjects received talazoparib capsules at a dose of 200 microgram per day (mcg/day) once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.

    Reporting group title
    Part 1: Talazoparib 400 mcg
    Reporting group description
    Subjects received talazoparib capsules at a dose of 400 microgram per day (mcg/day) once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.

    Reporting group title
    Part 1: Talazoparib 900 mcg
    Reporting group description
    Subjects received talazoparib capsules at a dose of 900 microgram per day (mcg/day) once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.

    Reporting group title
    Part 1: Talazoparib 600 mcg
    Reporting group description
    Subjects received talazoparib capsules at a dose of 600 microgram per day (mcg/day) once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.

    Reporting group title
    Part 1: Talazoparib 1000 mcg
    Reporting group description
    Subjects received talazoparib capsules at a dose of 1000 microgram per day (mcg/day) once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.

    Reporting group title
    Part 1: Talazoparib 1100 mcg
    Reporting group description
    Subjects received talazoparib capsules at a dose of 1100 microgram per day (mcg/day) once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.

    Reporting group title
    Part 2: Talazoparib (Breast Cancer)
    Reporting group description
    Subjects with breast cancer, received talazoparib capsules at the MTD as determined in Part 1 (1000 mcg/day), orally once daily in each 28-day treatment cycle (up to a maximum of 40 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.

    Reporting group title
    Part 2: Talazoparib (Ovarian/ Peritoneal Cancer)
    Reporting group description
    Subjects with ovarian/ peritoneal cancer, received talazoparib capsules at the MTD as determined in Part 1 (1000 mcg/day), orally once daily in each 28-day treatment cycle (up to a maximum of 40 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.

    Reporting group title
    Part 2: Talazoparib (Pancreatic Cancer)
    Reporting group description
    Subjects with pancreatic cancer, received talazoparib capsules at the MTD as determined in Part 1 (1000 mcg/day), orally once daily in each 28-day treatment cycle (up to a maximum of 40 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.

    Reporting group title
    Part 2: Talazoparib (Ewing Cancer)
    Reporting group description
    Subjects with ewing cancer, received talazoparib capsules at the MTD as determined in Part 1 (1000 mcg/day), orally once daily in each 28-day treatment cycle (up to a maximum of 40 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.

    Reporting group title
    Part 2: Talazoparib (SCLC Cancer)
    Reporting group description
    Subjects with SCLC cancer, received talazoparib capsules at the MTD as determined in Part 1 (1000 mcg/day), orally once daily in each 28-day treatment cycle (up to a maximum of 40 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.

    Reporting group title
    Part 2: Talazoparib (Prostate Cancer)
    Reporting group description
    Subjects with prostate cancer, received talazoparib capsules at the MTD as determined in Part 1 (1000 mcg/day), orally once daily in each 28-day treatment cycle (up to a maximum of 40 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met.

    Serious adverse events
    Part 1: Talazoparib 25 mcg Part 1: Talazoparib 50 mcg Part 1: Talazoparib 100 mcg Part 1: Talazoparib 200 mcg Part 1: Talazoparib 400 mcg Part 1: Talazoparib 900 mcg Part 1: Talazoparib 600 mcg Part 1: Talazoparib 1000 mcg Part 1: Talazoparib 1100 mcg Part 2: Talazoparib (Breast Cancer) Part 2: Talazoparib (Ovarian/ Peritoneal Cancer) Part 2: Talazoparib (Pancreatic Cancer) Part 2: Talazoparib (Ewing Cancer) Part 2: Talazoparib (SCLC Cancer) Part 2: Talazoparib (Prostate Cancer)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    1 / 3 (33.33%)
    2 / 3 (66.67%)
    2 / 3 (66.67%)
    3 / 3 (100.00%)
    0 / 3 (0.00%)
    3 / 6 (50.00%)
    2 / 6 (33.33%)
    2 / 6 (33.33%)
    3 / 6 (50.00%)
    2 / 12 (16.67%)
    5 / 11 (45.45%)
    6 / 10 (60.00%)
    4 / 12 (33.33%)
    8 / 23 (34.78%)
    0 / 3 (0.00%)
         number of deaths (all causes)
    0
    0
    0
    0
    0
    0
    0
    0
    2
    0
    0
    2
    2
    2
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    0
    0
    0
    0
    2
    0
    0
    2
    2
    2
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Invasive ductal breast carcinoma
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metastases to central nervous system
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 12 (0.00%)
    1 / 11 (9.09%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    1 / 23 (4.35%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancreatic carcinoma
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    1 / 10 (10.00%)
    0 / 12 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Tumour associated fever
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    1 / 10 (10.00%)
    0 / 12 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metastases to lung
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    1 / 23 (4.35%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Ovarian neoplasm
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    1 / 10 (10.00%)
    0 / 12 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cancer pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    1 / 12 (8.33%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Hypotension
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    1 / 23 (4.35%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Disease progression
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    1 / 10 (10.00%)
    0 / 12 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Pleural effusion
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 12 (8.33%)
    1 / 11 (9.09%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    2 / 12 (16.67%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Haemothorax
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    1 / 11 (9.09%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    1 / 12 (8.33%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Investigations
    Transaminases increased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    1 / 23 (4.35%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood sodium decreased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    1 / 23 (4.35%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Anastomotic stenosis
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Transfusion reaction
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    1 / 11 (9.09%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pubis fracture
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Supraventricular tachycardia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    1 / 23 (4.35%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ventricular tachycardia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 12 (8.33%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Neuralgia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    1 / 23 (4.35%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    1 / 12 (8.33%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Ascites
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 4
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abdominal pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    1 / 11 (9.09%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dyspepsia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intestinal obstruction
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 12 (8.33%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rectal haemorrhage
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    1 / 23 (4.35%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    2 / 11 (18.18%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Food poisoning
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    1 / 11 (9.09%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Bile duct obstruction
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyperbilirubinaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    1 / 10 (10.00%)
    0 / 12 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    1 / 23 (4.35%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haematuria
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Endocrine disorders
    Inappropriate antidiuretic hormone secretion
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    1 / 11 (9.09%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Bone pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Bacteraemia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    1 / 10 (10.00%)
    0 / 12 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Community acquired infection
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Device related infection
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    2 / 11 (18.18%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lung infection
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    1 / 23 (4.35%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Otitis media
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    1 / 12 (8.33%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    1 / 10 (10.00%)
    0 / 12 (0.00%)
    1 / 23 (4.35%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Hyponatraemia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    1 / 11 (9.09%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    1 / 23 (4.35%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypokalaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    1 / 11 (9.09%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    Part 1: Talazoparib 25 mcg Part 1: Talazoparib 50 mcg Part 1: Talazoparib 100 mcg Part 1: Talazoparib 200 mcg Part 1: Talazoparib 400 mcg Part 1: Talazoparib 900 mcg Part 1: Talazoparib 600 mcg Part 1: Talazoparib 1000 mcg Part 1: Talazoparib 1100 mcg Part 2: Talazoparib (Breast Cancer) Part 2: Talazoparib (Ovarian/ Peritoneal Cancer) Part 2: Talazoparib (Pancreatic Cancer) Part 2: Talazoparib (Ewing Cancer) Part 2: Talazoparib (SCLC Cancer) Part 2: Talazoparib (Prostate Cancer)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    3 / 3 (100.00%)
    3 / 3 (100.00%)
    3 / 3 (100.00%)
    3 / 3 (100.00%)
    3 / 3 (100.00%)
    6 / 6 (100.00%)
    6 / 6 (100.00%)
    6 / 6 (100.00%)
    6 / 6 (100.00%)
    12 / 12 (100.00%)
    11 / 11 (100.00%)
    10 / 10 (100.00%)
    12 / 12 (100.00%)
    20 / 23 (86.96%)
    3 / 3 (100.00%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Neoplasm skin
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Squamous cell carcinoma of skin
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    1 / 10 (10.00%)
    0 / 12 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    Vascular disorders
    Deep vein thrombosis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    1 / 11 (9.09%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    1
    0
    0
    0
    1
    0
    0
    0
    0
    Lymphostasis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Thrombosis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    0
    0
    0
    0
    0
    0
    0
    0
    Hot flush
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    1 / 12 (8.33%)
    1 / 11 (9.09%)
    1 / 10 (10.00%)
    0 / 12 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    1
    1
    1
    1
    0
    0
    0
    Lymphoedema
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    2 / 12 (16.67%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    2
    0
    0
    0
    0
    0
    Hypotension
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 12 (8.33%)
    1 / 11 (9.09%)
    1 / 10 (10.00%)
    0 / 12 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    1
    1
    0
    0
    0
    Haematoma
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    1 / 10 (10.00%)
    0 / 12 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    Superior vena cava syndrome
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    1 / 12 (8.33%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Surgical and medical procedures
    Tooth extraction
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Breast reconstruction
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Frontal sinus operation
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    1 / 23 (4.35%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    1
    0
    General disorders and administration site conditions
    Early satiety
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Fatigue
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    2 / 3 (66.67%)
    2 / 3 (66.67%)
    3 / 3 (100.00%)
    3 / 6 (50.00%)
    3 / 6 (50.00%)
    5 / 6 (83.33%)
    1 / 6 (16.67%)
    6 / 12 (50.00%)
    9 / 11 (81.82%)
    4 / 10 (40.00%)
    3 / 12 (25.00%)
    12 / 23 (52.17%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    3
    3
    3
    8
    6
    8
    1
    16
    22
    7
    5
    17
    0
    Chest pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 12 (8.33%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    1
    0
    0
    0
    0
    0
    Influenza like illness
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    1 / 12 (8.33%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    1
    0
    1
    0
    0
    0
    0
    0
    Mucosal inflammation
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    1 / 6 (16.67%)
    1 / 6 (16.67%)
    1 / 6 (16.67%)
    3 / 12 (25.00%)
    1 / 11 (9.09%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    1
    4
    1
    3
    1
    0
    0
    0
    0
    Pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    2 / 6 (33.33%)
    1 / 6 (16.67%)
    1 / 6 (16.67%)
    2 / 12 (16.67%)
    1 / 11 (9.09%)
    1 / 10 (10.00%)
    0 / 12 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    1
    1
    2
    1
    1
    0
    0
    0
    Peripheral swelling
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    1 / 10 (10.00%)
    0 / 12 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    2
    0
    0
    0
    Asthenia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    1 / 12 (8.33%)
    1 / 23 (4.35%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    1
    0
    0
    0
    1
    2
    0
    Axillary pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    1 / 12 (8.33%)
    1 / 11 (9.09%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    2
    0
    1
    1
    0
    0
    0
    0
    Catheter site pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    2 / 11 (18.18%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    4
    0
    0
    0
    0
    Chest discomfort
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    1 / 11 (9.09%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    1 / 23 (4.35%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    1
    0
    0
    1
    0
    Chills
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    1 / 10 (10.00%)
    0 / 12 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    1
    0
    0
    0
    Local swelling
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    2
    0
    0
    0
    0
    0
    0
    Medical device site reaction
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Oedema peripheral
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    4 / 11 (36.36%)
    0 / 10 (0.00%)
    2 / 12 (16.67%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    4
    0
    2
    0
    0
    Pyrexia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    3 / 6 (50.00%)
    0 / 6 (0.00%)
    3 / 6 (50.00%)
    1 / 6 (16.67%)
    2 / 12 (16.67%)
    2 / 11 (18.18%)
    2 / 10 (20.00%)
    1 / 12 (8.33%)
    1 / 23 (4.35%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    3
    0
    3
    4
    2
    2
    5
    1
    1
    0
    Discomfort
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    1 / 11 (9.09%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Feeling hot
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    3 / 11 (27.27%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    3
    0
    0
    0
    0
    Sensation of foreign body
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 12 (8.33%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Temperature intolerance
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    1 / 11 (9.09%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Feeling abnormal
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    1 / 23 (4.35%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Feeling cold
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    1 / 23 (4.35%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Localised oedema
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    1 / 23 (4.35%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Nodule
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    1 / 10 (10.00%)
    1 / 12 (8.33%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    1
    0
    0
    Oedema
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    1 / 23 (4.35%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Thirst
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    1 / 12 (8.33%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Immune system disorders
    Seasonal allergy
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Autoimmune disorder
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Reproductive system and breast disorders
    Genital discomfort
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Penile pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    0
    0
    0
    0
    0
    0
    0
    0
    Vaginal haemorrhage
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    2 / 11 (18.18%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    1 / 23 (4.35%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    2
    0
    0
    0
    3
    0
    0
    1
    0
    Breast pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    2
    0
    0
    0
    0
    0
    0
    0
    Nipple pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Adnexa uteri pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 12 (8.33%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Pelvic pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    1 / 11 (9.09%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 23 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    1
    Prostatic pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 23 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Vulvovaginal dryness
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 12 (8.33%)
    1 / 11 (9.09%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    1
    0
    0
    0
    0
    Vulvovaginal pruritus
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    1 / 11 (9.09%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Breast tenderness
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    1 / 12 (8.33%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Vulvovaginal discomfort
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    1 / 23 (4.35%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    2 / 6 (33.33%)
    3 / 6 (50.00%)
    1 / 6 (16.67%)
    3 / 6 (50.00%)
    2 / 12 (16.67%)
    4 / 11 (36.36%)
    0 / 10 (0.00%)
    3 / 12 (25.00%)
    4 / 23 (17.39%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0