Flag of the European Union EU Clinical Trials Register Help

Clinical trials

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

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

    The EU Clinical Trials Register currently displays   43861   clinical trials with a EudraCT protocol, of which   7284   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

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

    < Back to search results

    Download PDF

    Clinical Trial Results:
    ARIEL4 (Assessment of Rucaparib In Ovarian CancEr TriaL): A Phase 3 Multicenter, Randomized Study of Rucaparib versus Chemotherapy in Patients with Relapsed, BRCA-Mutant, High-Grade Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

    Summary
    EudraCT number
    		 2016-000816-14
    Trial protocol
    		 GB   HU   CZ   ES   PL   IT  
    Global end of trial date

    Results information
    Results version number
    		 v1(current)
    This version publication date
    29 Mar 2022
    First version publication date
    29 Mar 2022
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    CO-338-043
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02855944
    WHO universal trial number (UTN)
    		 -
    Other trial identifiers
    		 IND number: 106289
    Sponsors
    Sponsor organisation name
    Clovis Oncology, Inc.
    Sponsor organisation address
    5500 Flatiron Parkway, Suite 100, Boulder, CO, United States, 80301
    Public contact
    Dr Lindsey Rolfe, Clovis Oncology, Inc., +44 12233 645500, lrolfe@clovisoncology.com
    Scientific contact
    Dr Lindsey Rolfe, Clovis Oncology, Inc., +44 12233 645500, lrolfe@clovisoncology.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
    30 Sep 2020
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    30 Sep 2020
    Global end of trial reached?
    No
    General information about the trial
    Main objective of the trial
    To determine investigator-assessed progression-free survival (invPFS) by RECIST Version 1.1 for rucaparib versus chemotherapy.
    Protection of trial subjects
    The following safety assessments were performed: adverse events, physical examinations, clinical laboratory evaluations (hematology, serum chemistry), vital signs, 12-lead ECGs, ECOG performance status. Patients were assessed for disease status per RECIST v1.1 every 8 calendar weeks following initiation of study treatment on Day 1 of Cycle 1. Patients experiencing disease progression by RECIST v1.1, as assessed by the investigator, were discontinued from treatment and entered follow-up.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    01 Mar 2017
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Safety, Efficacy
    Long term follow-up duration
    		 6 Years
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Brazil: 43
    Country: Number of subjects enrolled
    Canada: 7
    Country: Number of subjects enrolled
    Israel: 8
    Country: Number of subjects enrolled
    Russian Federation: 113
    Country: Number of subjects enrolled
    Ukraine: 41
    Country: Number of subjects enrolled
    United States: 3
    Country: Number of subjects enrolled
    Poland: 11
    Country: Number of subjects enrolled
    Spain: 10
    Country: Number of subjects enrolled
    United Kingdom: 32
    Country: Number of subjects enrolled
    Czechia: 25
    Country: Number of subjects enrolled
    Hungary: 12
    Country: Number of subjects enrolled
    Italy: 44
    Worldwide total number of subjects
    349
    EEA total number of subjects
    102
    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)
    277
    From 65 to 84 years
    71
    85 years and over
    1

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 A total of 349 patients from 64 sites across 12 countries were enrolled in the initial Treatment Part of the study and randomized to receive rucaparib or chemotherapy. Patients randomized to chemotherapy had the option to cross over to receive rucaparib in the Crossover Part of the study upon progression of disease.

    Pre-assignment
    Screening details
    		 The study enrolled patients with a deleterious BRCA1/2 mutation and who had received at least 2 prior chemotherapy regimens, with at least 1 regimen including a platinum. Patients with confirmation of all other eligibility criteria in the screening phase were randomized 2:1 to receive rucaparib or chemotherapy.

    Period 1
    Period 1 title
    Period 1 - Treatment
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Rucaparib
    Arm description
    		 Patients randomized to the rucaparib arm received oral rucaparib 600 mg twice a day (BID) in continuous 28- day cycles.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Rucaparib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Patients randomized to the rucaparib arm received oral rucaparib 600 mg BID in continuous 28-day cycles. Patients were to take rucaparib with or without food.

    Arm title
    		 Chemotherapy
    Arm description
    		 Patients randomized to the chemotherapy arm received either weekly intravenous (IV) paclitaxel or IV platinum-based chemotherapy per investigator choice and per standard of care. Patients with platinum-resistant or partially platinum-sensitive disease received weekly paclitaxel. The starting dose of weekly paclitaxel was 60 to 80 mg/m2 administered via IV infusion (ie, on Days 1, 8, and 15) in each 28-day cycle (with a week break from dosing on Day 22 in each cycle). The dosage and administration of single-agent cisplatin or carboplatin or doublet carboplatin/paclitaxel, carboplatin/gemcitabine, or cisplatin/gemcitabine IV infusion followed institutional guidelines for each agent. Upon progression of disease, patients had the option to cross over to rucaparib and receive oral rucaparib 600 mg BID in continuous 28-day cycles.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Paclitaxel
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection/infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    The starting dose of weekly paclitaxel was 60 to 80 mg/m2 administered via IV infusion (ie, on Days 1, 8, and 15) in each 28-day cycle (with a week break from dosing on Day 22 in each cycle).

    Investigational medicinal product name
    Cisplatin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection/infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    The dosage, dosing schedule, and administration of single-agent cisplatin or carboplatin, or doublet carboplatin/paclitaxel, carboplatin/gemcitabine, or cisplatin/gemcitabine IV infusion followed institutional guidelines for each agent. No more than 8 cycles of platinum monotherapy or doublet therapy were to be administered in this study. Patients received the same chemotherapy in 21-day or 28-day cycles, as appropriate, throughout the study.

    Investigational medicinal product name
    Carboplatin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection/infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    The dosage, dosing schedule, and administration of single-agent cisplatin or carboplatin, or doublet carboplatin/paclitaxel, carboplatin/gemcitabine, or cisplatin/gemcitabine IV infusion followed institutional guidelines for each agent. No more than 8 cycles of platinum monotherapy or doublet therapy were to be administered in this study. Patients received the same chemotherapy in 21-day or 28-day cycles, as appropriate, throughout the study.

    Investigational medicinal product name
    Gemcitabine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection/infusion
    Routes of administration
    Infusion
    Dosage and administration details
    The dosage, dosing schedule, and administration of single-agent cisplatin or carboplatin, or doublet carboplatin/paclitaxel, carboplatin/gemcitabine, or cisplatin/gemcitabine IV infusion followed institutional guidelines for each agent. No more than 8 cycles of platinum monotherapy or doublet therapy were to be administered in this study. Patients received the same chemotherapy in 21-day or 28-day cycles, as appropriate, throughout the study.

    Number of subjects in period 1
    		Rucaparib Chemotherapy
    Started
    233
    116
    Completed
    188
    108
    Not completed
    45
    8
         Ongoing
    44
    5
         Discontinued prior to starting study drug
    1
    3
    Period 2
    Period 2 title
    Period 2 - Crossover to Rucaparib
    Is this the baseline period?
    		 No
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Arm title
    		 Rucaparib
    Arm description
    		 Upon progression of disease, patients initially randomized to the chemotherapy arm had the option to cross over to rucaparib and receive oral rucaparib 600 mg BID in continuous 28-day cycles.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Rucaparib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Patients who crossed over to rucaparib received oral rucaparib 600 mg BID in continuous 28-day cycles. Patients were to take rucaparib with or without food.

    Number of subjects in period 2 [1]
    		Rucaparib
    Started
    74
    Completed
    47
    Not completed
    27
         Ongoing
    27
    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: Upon progression of disease in Period 1, patients had the option to cross over to rucaparib.

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Rucaparib
    Reporting group description
    		 Patients randomized to the rucaparib arm received oral rucaparib 600 mg twice a day (BID) in continuous 28- day cycles.

    Reporting group title
    Chemotherapy
    Reporting group description
    		 Patients randomized to the chemotherapy arm received either weekly intravenous (IV) paclitaxel or IV platinum-based chemotherapy per investigator choice and per standard of care. Patients with platinum-resistant or partially platinum-sensitive disease received weekly paclitaxel. The starting dose of weekly paclitaxel was 60 to 80 mg/m2 administered via IV infusion (ie, on Days 1, 8, and 15) in each 28-day cycle (with a week break from dosing on Day 22 in each cycle). The dosage and administration of single-agent cisplatin or carboplatin or doublet carboplatin/paclitaxel, carboplatin/gemcitabine, or cisplatin/gemcitabine IV infusion followed institutional guidelines for each agent. Upon progression of disease, patients had the option to cross over to rucaparib and receive oral rucaparib 600 mg BID in continuous 28-day cycles.

    Reporting group values
    		 Rucaparib Chemotherapy Total
    Number of subjects
    		 233 116 349
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    		 0
        From 65-84 years
    		 0
        85 years and over
    		 0
    Age continuous
    Units: years
        median (full range (min-max))
    		 58.0 (38 to 81) 58.5 (38 to 85) -
    Gender categorical
    Units: Subjects
        Female
    		 233 116 349
        Male
    		 0 0 0
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    		 1 0 1
        Asian
    		 3 0 3
        Native Hawaiian or Other Pacific Islander
    		 0 0 0
        Black or African American
    		 4 2 6
        White
    		 219 113 332
        More than one race
    		 1 0 1
        Unknown or Not Reported
    		 5 1 6
    ECOG at Baseline
    Measure Description: Eastern Cooperative Oncology Group (ECOG) Performance Status Scale. ECOG 0 = Fully active, able to carry on all pre-disease performance without restriction. ECOG 1 = Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature (eg, light house work or office work).
    Units: Subjects
        ECOG 0
    		 125 72 197
        ECOG 1
    		 108 44 152
    Number of Prior Chemotherapy Regimens
    Units: Subjects
        =2
    		 134 68 202
        =3
    		 58 28 86
        =4
    		 23 11 34
        =5
    		 7 5 12
        >5
    		 11 4 15
    Number of Prior Platinum Regimens
    Units: Subjects
        =1
    		 12 6 18
        =2
    		 156 74 230
        =3
    		 48 28 76
        =4
    		 11 7 18
        =5
    		 2 1 3
        >5
    		 4 0 4
    Randomization Stratification: Platinum Status
    Platinum resistant: patients who progressed ≥ 1 to < 6 months after the last dose of platinum-based chemotherapy; Partially platinum sensitive: patients who progressed ≥ 6 to < 12 months after last dose of platinum-based chemotherapy; Platinum sensitive: patients who progressed ≥ 12 months after last dose of platinum-based chemotherapy
    Units: Subjects
        Platinum resistant
    		 120 59 179
        Partially platinum sensitive
    		 65 31 96
        Platinum sensitive
    		 48 26 74
    Combined Local and Central Lab BRCA Mutation Results
    BRCA1: patients with a deleterious breast cancer susceptibility gene 1 (BRCA1) mutation in their tumor; BRCA2: patients with a deleterious breast cancer susceptibility gene 2 (BRCA2) mutation in their tumor; Non-BRCA: patients without a BRCA mutation in their tumor
    Units: Subjects
        BRCA1
    		 181 79 260
        BRCA2
    		 52 36 88
        Non-BRCA
    		 0 1 1
    Mutation Type
    Units: Subjects
        Germline
    		 198 95 293
        Somatic
    		 35 19 54
        Not Available
    		 0 2 2
    Patients with a BRCA Reversion Mutation
    Units: Subjects
        With reversion
    		 13 10 23
        Without reversion
    		 220 106 326

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Rucaparib
    Reporting group description
    		 Patients randomized to the rucaparib arm received oral rucaparib 600 mg twice a day (BID) in continuous 28- day cycles.

    Reporting group title
    Chemotherapy
    Reporting group description
    		 Patients randomized to the chemotherapy arm received either weekly intravenous (IV) paclitaxel or IV platinum-based chemotherapy per investigator choice and per standard of care. Patients with platinum-resistant or partially platinum-sensitive disease received weekly paclitaxel. The starting dose of weekly paclitaxel was 60 to 80 mg/m2 administered via IV infusion (ie, on Days 1, 8, and 15) in each 28-day cycle (with a week break from dosing on Day 22 in each cycle). The dosage and administration of single-agent cisplatin or carboplatin or doublet carboplatin/paclitaxel, carboplatin/gemcitabine, or cisplatin/gemcitabine IV infusion followed institutional guidelines for each agent. Upon progression of disease, patients had the option to cross over to rucaparib and receive oral rucaparib 600 mg BID in continuous 28-day cycles.
    Reporting group title
    Rucaparib
    Reporting group description
    		 Upon progression of disease, patients initially randomized to the chemotherapy arm had the option to cross over to rucaparib and receive oral rucaparib 600 mg BID in continuous 28-day cycles.

    Primary: Investigator Assessed Progression-Free Survival (invPFS) by RECIST Version 1.1 for Rucaparib Versus Chemotherapy (Efficacy Population)

    		 Close Top of page
    End point title
    		 Investigator Assessed Progression-Free Survival (invPFS) by RECIST Version 1.1 for Rucaparib Versus Chemotherapy (Efficacy Population)
    End point description
    The primary efficacy endpoint is invPFS for the Treatment Part of the study. The time to invPFS is calculated in months as the time from randomization to disease progression +1 day, as determined by RECIST v1.1 (Response Evaluation Criteria in Solid Tumors) criteria or death due to any cause, whichever occurs first. Progression is defined using RECIST v1.1, as at least a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Efficacy Population - All randomized patients in the treatment part of study with a deleterious BRCA mutation, excluding those identified to have a BRCA reversion mutation.
    End point type
    Primary
    End point timeframe
    Assessments every 8 weeks from Cycle 1 Day 1 (C1D1) until disease progression, death, or initiation of subsequent treatment. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3.5 years.
    End point values
    		 Rucaparib Chemotherapy
    Number of subjects analysed
    220
    105
    Units: Months
        median (confidence interval 95%)
    7.4 (7.3 to 9.1)
    5.7 (5.5 to 7.3)
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Rucaparib v Chemotherapy
    Number of subjects included in analysis
    325
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.001
    Method
    		 Regression, Cox
    Parameter type
    		 Cox proportional hazard
    Point estimate
    0.639
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.489
         upper limit
    		 0.835

    Primary: Investigator Assessed Progression-Free Survival (invPFS) by RECIST Version 1.1 for Rucaparib Versus Chemotherapy (ITT Population)

    		 Close Top of page
    End point title
    		 Investigator Assessed Progression-Free Survival (invPFS) by RECIST Version 1.1 for Rucaparib Versus Chemotherapy (ITT Population)
    End point description
    The primary efficacy endpoint is invPFS for the Treatment Part of the study. The time to invPFS is calculated in months as the time from randomization to disease progression +1 day, as determined by RECIST v1.1 (Response Evaluation Criteria in Solid Tumors) criteria or death due to any cause, whichever occurs first. Progression is defined using RECIST v1.1, as at least a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Intent-to-treat (ITT) Population - All randomized patients in the treatment part of study.
    End point type
    Primary
    End point timeframe
    Assessments every 8 weeks from C1D1 until disease progression, death, or initiation of subsequent treatment. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3.5 years.
    End point values
    		 Rucaparib Chemotherapy
    Number of subjects analysed
    233
    116
    Units: Months
        median (confidence interval 95%)
    7.4 (6.7 to 7.9)
    5.7 (5.5 to 6.7)
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Rucaparib v Chemotherapy
    Number of subjects included in analysis
    349
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0017
    Method
    		 Regression, Cox
    Parameter type
    		 Cox proportional hazard
    Point estimate
    0.665
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.516
         upper limit
    		 0.858

    Secondary: Investigator Assessed Overall Response Rate (ORR) by RECIST v1.1 (Efficacy Population)

    		 Close Top of page
    End point title
    		 Investigator Assessed Overall Response Rate (ORR) by RECIST v1.1 (Efficacy Population)
    End point description
    A secondary endpoint is the ORR for the Treatment Part of the study. ORR is defined as the percentage of patients with a confirmed CR (complete response) or PR (partial response) by RECIST v1.1. The confirmed response is defined as a CR or PR on subsequent tumor assessment at least 28 days after first response documentation. CR is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR is at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameter. Efficacy population with measurable disease at baseline. Efficacy population defined as all randomized patients with a deleterious BRCA mutation, excluding those identified to have a BRCA reversion mutation.
    End point type
    Secondary
    End point timeframe
    Assessments every 8 weeks from C1D1 until disease progression, death, or initiation of subsequent treatment. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3.5 years
    End point values
    		 Rucaparib Chemotherapy
    Number of subjects analysed
    211
    96
    Units: Percentage of patients
        number (confidence interval 95%)
    40.3 (33.6 to 47.2)
    32.3 (23.1 to 42.6)
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    The stratified Cochran-Mantzel-Haenszel (CMH) test was used to test the difference in proportions between treatment adjusting for the randomization strata for the PFI after most recent platinum-containing therapy (ie, platinum resistant, partially platinum-sensitive, or platinum sensitive).
    Comparison groups
    Rucaparib v Chemotherapy
    Number of subjects included in analysis
    307
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1287
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval

    Secondary: Investigator Assessed Overall Response Rate (ORR) by RECIST v1.1 (ITT Population)

    		 Close Top of page
    End point title
    		 Investigator Assessed Overall Response Rate (ORR) by RECIST v1.1 (ITT Population)
    End point description
    A secondary endpoint is the ORR for the Treatment Part of the study. ORR is defined as the percentage of patients with a confirmed CR (complete response) or PR (partial response) by RECIST v1.1. The confirmed response is defined as a CR or PR on subsequent tumor assessment at least 28 days after first response documentation. CR is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR is at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameter. Intent-to-treat (ITT) population with measurable disease at baseline. ITT population defined as all randomized patients.
    End point type
    Secondary
    End point timeframe
    Assessments every 8 weeks from C1D1 until disease progression, death, or initiation of subsequent treatment. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3.5 years.
    End point values
    		 Rucaparib Chemotherapy
    Number of subjects analysed
    224
    106
    Units: Percentage of patients
        number (confidence interval 95%)
    37.9 (31.6 to 44.7)
    30.2 (21.7 to 39.9)
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    The stratified CMH test was used to test the difference in proportions between treatment adjusting for the randomization strata for the progression-free interval after most recent platinum-containing therapy (ie, platinum resistant, partially platinum-sensitive, or platinum sensitive).
    Comparison groups
    Rucaparib v Chemotherapy
    Number of subjects included in analysis
    330
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.125
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval

    Secondary: Investigator Assessed Duration of Response (DOR) by RECIST v1.1 (Efficacy Population)

    		 Close Top of page
    End point title
    		 Investigator Assessed Duration of Response (DOR) by RECIST v1.1 (Efficacy Population)
    End point description
    A secondary endpoint is the DOR for the Treatment Part of the study. The DOR as assessed by investigator is analyzed in the subgroup of patients who had a confirmed response by RECIST v1.1. DOR for any confirmed RECIST CR or PR will be measured from the date of the first response until the first date that progressive disease (PD) is documented. DOR is calculated in months as the time from the first date of the scan showing a response to the first scan with disease progression +1 day. Any patients with an ongoing response are censored at the date of the last post-baseline scan. Only tumor scans up to and within 6 weeks of start of any subsequent anti-cancer treatment are included. Progressive disease (PD) is defined using RECIST v1.1, as at least a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a nontarget lesion, or the appearance of new lesions. Efficacy population with measurable disease at baseline and a confirmed response.
    End point type
    Secondary
    End point timeframe
    Assessments every 8 weeks from C1D1 until disease progression, death, or initiation of subsequent treatment. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3.5 years.
    End point values
    		 Rucaparib Chemotherapy
    Number of subjects analysed
    85
    31
    Units: Months
        median (confidence interval 95%)
    9.4 (7.5 to 11.1)
    7.2 (4.0 to 11.4)
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Rucaparib v Chemotherapy
    Number of subjects included in analysis
    116
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0401
    Method
    		 Regression, Cox
    Parameter type
    		 Cox proportional hazard
    Point estimate
    0.589
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.356
         upper limit
    		 0.976

    Secondary: Investigator Assessed Duration of Response (DOR) by RECIST v1.1 (ITT Population)

    		 Close Top of page
    End point title
    		 Investigator Assessed Duration of Response (DOR) by RECIST v1.1 (ITT Population)
    End point description
    A secondary endpoint is the DOR for the Treatment Part of the study. The DOR as assessed by investigator is analyzed in the subgroup of patients who had a confirmed response by RECIST v1.1. DOR for any confirmed RECIST CR or PR will be measured from the date of the first response until the first date that progressive disease (PD) is documented. DOR is calculated in months as the time from the first date of the scan showing a response to the first scan with disease progression +1 day. Any patients with an ongoing response are censored at the date of the last post-baseline scan. Only tumor scans up to and within 6 weeks of start of any subsequent anti-cancer treatment are included. Progressive disease (PD) is defined using RECIST v1.1, as at least a 20% increase in the sum of the longest diameter of target lesions, or measurable increase in a nontarget lesion, or the appearance of new lesions. Intent-to-treat (ITT) population with measurable disease at baseline and confirmed response.
    End point type
    Secondary
    End point timeframe
    Assessments every 8 weeks from C1D1 until disease progression, death, or initiation of subsequent treatment. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3.5 years.
    End point values
    		 Rucaparib Chemotherapy
    Number of subjects analysed
    85
    32
    Units: Months
        median (confidence interval 95%)
    9.4 (7.5 to 11.1)
    7.2 (3.9 to 9.4)
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Rucaparib v Chemotherapy
    Number of subjects included in analysis
    117
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.024
    Method
    		 Regression, Cox
    Parameter type
    		 Cox proportional hazard
    Point estimate
    0.564
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.343
         upper limit
    		 0.927

    Secondary: Investigator Assessed Overall Response Rate (ORR) by RECIST v1.1 and/or CA-125 Response (Efficacy Population)

    		 Close Top of page
    End point title
    		 Investigator Assessed Overall Response Rate (ORR) by RECIST v1.1 and/or CA-125 Response (Efficacy Population)
    End point description
    A secondary endpoint is ORR for the Treatment Part of the study defined as the percentage of patients with best response of CR or PR using RECIST v1.1 or response per Gynecologic Cancer InterGroup Cancer Antigen 125 (GCIG CA-125) criteria. CR is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR is at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameter. Response to CA-125 has occurred if there is at least a 50% decrease from baseline: 1. in a sample collected after initiation of study treatment AND 2. that is confirmed in a subsequent sample collected ≥21 days after the prior sample. The absolute value of this confirmatory sample must be ≤110% of the prior sample. The date when the first sample with a 50% decrease from baseline is observed is the date of the CA-125 response.
    End point type
    Secondary
    End point timeframe
    Assessments every 8 weeks from C1D1 until disease progression, death, or initiation of subsequent treatment. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3.5 years.
    End point values
    		 Rucaparib Chemotherapy
    Number of subjects analysed
    217
    101
    Units: Percentage of patients
        number (confidence interval 95%)
    50.7 (43.8 to 57.5)
    43.6 (33.7 to 53.8)
    No statistical analyses for this end point

    Secondary: Investigator Assessed Overall Response Rate (ORR) by RECIST v1.1 and/or CA-125 Response (ITT Population)

    		 Close Top of page
    End point title
    		 Investigator Assessed Overall Response Rate (ORR) by RECIST v1.1 and/or CA-125 Response (ITT Population)
    End point description
    A secondary endpoint is ORR for the Treatment Part of the study defined as the percentage of patients with best response of CR or PR using RECIST v1.1 or response per Gynecologic Cancer InterGroup Cancer Antigen 125 (GCIG CA-125) criteria. CR is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR is at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameter. Response to CA-125 has occurred if there is at least a 50% decrease from baseline: 1. in a sample collected after initiation of study treatment AND 2. that is confirmed in a subsequent sample collected ≥21 days after the prior sample. The absolute value of this confirmatory sample must be ≤110% of the prior sample. The date when the first sample with a 50% decrease from baseline is observed is the date of the CA-125 response.
    End point type
    Secondary
    End point timeframe
    Assessments every 8 weeks from C1D1 until disease progression, death, or initiation of subsequent treatment. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3.5 years.
    End point values
    		 Rucaparib Chemotherapy
    Number of subjects analysed
    230
    111
    Units: Percentage of patients
        number (confidence interval 95%)
    47.8 (41.2 to 54.5)
    40.5 (31.3 to 50.3)
    No statistical analyses for this end point

    Secondary: Least Squares Mean Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Global Health Status Score for the First 6 Cycles (Efficacy Population)

    		 Close Top of page
    End point title
    		 Least Squares Mean Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Global Health Status Score for the First 6 Cycles (Efficacy Population)
    End point description
    EORTC QLQ-C30 is a questionnaire that rates the overall quality of life in cancer patients. The first 28 questions use a 4-point scale (1=not at all to 4=very much) for evaluating function (physical, role, social, cognitive, emotional), symptoms (diarrhea, fatigue, dyspnea, appetite loss, insomnia, nausea/vomiting, constipation, and pain) and financial difficulties. The last 2 questions use a 7-point scale (1=very poor to 7=excellent) to evaluate overall health and quality of life. Global scores are converted to a score of 0 to 100, with a higher score indicating improved health status. Mean changes from baseline global score over the first 6 cycles in the Treatment Part of the study were analyzed. Efficacy population - All randomized patients with a deleterious BRCA mutation, excluding those identified to have a BRCA reversion mutation, and with a baseline value and at least one post-baseline value for the EORTC QLQ-C30 Global Health Status score during the first 6 cycles.
    End point type
    Secondary
    End point timeframe
    Baseline to the end of Cycle 6, or up to approximately 6 months
    End point values
    		 Rucaparib Chemotherapy
    Number of subjects analysed
    197
    91
    Units: Score on a scale
        least squares mean (standard error)
    0.5 ( 0.55 )
    0.3 ( 0.86 )
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Chemotherapy v Rucaparib
    Number of subjects included in analysis
    288
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.8528
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.8
         upper limit
    		 2.2

    Secondary: Least Squares Mean Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Global Health Status Score for the First 6 Cycles (ITT Population)

    		 Close Top of page
    End point title
    		 Least Squares Mean Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Global Health Status Score for the First 6 Cycles (ITT Population)
    End point description
    EORTC QLQ-C30 is a questionnaire that rates the overall quality of life in cancer patients. The first 28 questions use a 4-point scale (1=not at all to 4=very much) for evaluating function (physical, role, social, cognitive, emotional), symptoms (diarrhea, fatigue, dyspnea, appetite loss, insomnia, nausea/vomiting, constipation, and pain) and financial difficulties. The last 2 questions use a 7-point scale (1=very poor to 7=excellent) to evaluate overall health and quality of life. Global scores are converted to a score of 0 to 100, with a higher score indicating improved health status. Mean changes from baseline global score over the first 6 cycles in the Treatment Part of the study were analyzed. Intent-to-treat (ITT) population - All randomized patients with a baseline value and at least one post-baseline value for the EORTC QLQ-C30 Global Health Status score during the first 6 cycles.
    End point type
    Secondary
    End point timeframe
    Baseline to the end of Cycle 6, or up to approximately 6 months
    End point values
    		 Rucaparib Chemotherapy
    Number of subjects analysed
    207
    101
    Units: Score on a scale
        least squares mean (standard error)
    0.6 ( 0.54 )
    0.4 ( 0.82 )
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Rucaparib v Chemotherapy
    Number of subjects included in analysis
    308
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.7742
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.6
         upper limit
    		 2.2

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years.
    Adverse event reporting additional description
    Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    23.0
    Reporting groups
    Reporting group title
    Rucaparib (Treatment Part)
    Reporting group description
    		 Patients randomized to the rucaparib arm in the Treatment Part of the study.

    Reporting group title
    Chemotherapy (Treatment Part)
    Reporting group description
    		 Patients randomized to the chemotherapy arm in the Treatment Part of the study.

    Reporting group title
    Rucaparib (Crossover Part)
    Reporting group description
    		 Patients randomized to chemotherapy who then crossed over upon disease progression and were treated with rucaparib.

    Serious adverse events
    		 Rucaparib (Treatment Part) Chemotherapy (Treatment Part) Rucaparib (Crossover Part)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    62 / 232 (26.72%)
    13 / 113 (11.50%)
    17 / 74 (22.97%)
         number of deaths (all causes)
    15
    3
    2
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Intraductal proliferative breast lesion
         subjects affected / exposed
    1 / 232 (0.43%)
    0 / 113 (0.00%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Malignant neoplasm progression
         subjects affected / exposed
    5 / 232 (2.16%)
    2 / 113 (1.77%)
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 5
    0 / 2
    0 / 1
    Myelodysplastic syndrome
         subjects affected / exposed
    1 / 232 (0.43%)
    0 / 113 (0.00%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Vascular disorders
    Deep vein thrombosis
         subjects affected / exposed
    3 / 232 (1.29%)
    1 / 113 (0.88%)
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Death
         subjects affected / exposed
    3 / 232 (1.29%)
    0 / 113 (0.00%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 3
    0 / 0
    0 / 0
    General physical health deterioration
         subjects affected / exposed
    2 / 232 (0.86%)
    0 / 113 (0.00%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Incarcerated hernia
         subjects affected / exposed
    0 / 232 (0.00%)
    0 / 113 (0.00%)
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    1 / 232 (0.43%)
    0 / 113 (0.00%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Immune system disorders
    Drug hypersensitivity
         subjects affected / exposed
    0 / 232 (0.00%)
    1 / 113 (0.88%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Fibrocystic breast disease
         subjects affected / exposed
    1 / 232 (0.43%)
    0 / 113 (0.00%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory failure
         subjects affected / exposed
    1 / 232 (0.43%)
    0 / 113 (0.00%)
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Pleural effusion
         subjects affected / exposed
    1 / 232 (0.43%)
    0 / 113 (0.00%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia aspiration
         subjects affected / exposed
    1 / 232 (0.43%)
    0 / 113 (0.00%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    1 / 232 (0.43%)
    1 / 113 (0.88%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    Pulmonary oedema
         subjects affected / exposed
    1 / 232 (0.43%)
    0 / 113 (0.00%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    1 / 232 (0.43%)
    0 / 113 (0.00%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood alkaline phosphatase increased
         subjects affected / exposed
    1 / 232 (0.43%)
    0 / 113 (0.00%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood creatinine increased
         subjects affected / exposed
    1 / 232 (0.43%)
    0 / 113 (0.00%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Platelet count decreased
         subjects affected / exposed
    2 / 232 (0.86%)
    0 / 113 (0.00%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Femur fracture
         subjects affected / exposed
    0 / 232 (0.00%)
    0 / 113 (0.00%)
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infusion related reaction
         subjects affected / exposed
    0 / 232 (0.00%)
    1 / 113 (0.88%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Post procedural fever
         subjects affected / exposed
    1 / 232 (0.43%)
    0 / 113 (0.00%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Radius fracture
         subjects affected / exposed
    1 / 232 (0.43%)
    0 / 113 (0.00%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Seroma
         subjects affected / exposed
    1 / 232 (0.43%)
    0 / 113 (0.00%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tibia fracture
         subjects affected / exposed
    1 / 232 (0.43%)
    0 / 113 (0.00%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Cardiac disorder
         subjects affected / exposed
    1 / 232 (0.43%)
    0 / 113 (0.00%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Pericardial effusion
         subjects affected / exposed
    1 / 232 (0.43%)
    0 / 113 (0.00%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Cerebrovascular accident
         subjects affected / exposed
    1 / 232 (0.43%)
    0 / 113 (0.00%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Depressed level of consciousness
         subjects affected / exposed
    1 / 232 (0.43%)
    0 / 113 (0.00%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    1 / 232 (0.43%)
    0 / 113 (0.00%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sciatica
         subjects affected / exposed
    0 / 232 (0.00%)
    0 / 113 (0.00%)
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    0 / 232 (0.00%)
    1 / 113 (0.88%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    0 / 232 (0.00%)
    1 / 113 (0.88%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anemia
         subjects affected / exposed
    19 / 232 (8.19%)
    2 / 113 (1.77%)
    4 / 74 (5.41%)
         occurrences causally related to treatment / all
    0 / 29
    0 / 3
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Febrile neutropenia
         subjects affected / exposed
    1 / 232 (0.43%)
    0 / 113 (0.00%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Leukopenia
         subjects affected / exposed
    1 / 232 (0.43%)
    0 / 113 (0.00%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Neutropenia
         subjects affected / exposed
    4 / 232 (1.72%)
    0 / 113 (0.00%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Pancytopenia
         subjects affected / exposed
    0 / 232 (0.00%)
    0 / 113 (0.00%)
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    5 / 232 (2.16%)
    1 / 113 (0.88%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal distension
         subjects affected / exposed
    1 / 232 (0.43%)
    0 / 113 (0.00%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Abdominal pain
         subjects affected / exposed
    1 / 232 (0.43%)
    0 / 113 (0.00%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ascites
         subjects affected / exposed
    2 / 232 (0.86%)
    0 / 113 (0.00%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    1 / 232 (0.43%)
    0 / 113 (0.00%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    1 / 232 (0.43%)
    0 / 113 (0.00%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dolichocolon acquired
         subjects affected / exposed
    1 / 232 (0.43%)
    0 / 113 (0.00%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 232 (0.00%)
    1 / 113 (0.88%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haematemesis
         subjects affected / exposed
    1 / 232 (0.43%)
    0 / 113 (0.00%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ileus
         subjects affected / exposed
    1 / 232 (0.43%)
    0 / 113 (0.00%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Intestinal obstruction
         subjects affected / exposed
    5 / 232 (2.16%)
    0 / 113 (0.00%)
    4 / 74 (5.41%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Large intestinal obstruction
         subjects affected / exposed
    0 / 232 (0.00%)
    1 / 113 (0.88%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Large intestine perforation
         subjects affected / exposed
    1 / 232 (0.43%)
    0 / 113 (0.00%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Megacolon
         subjects affected / exposed
    1 / 232 (0.43%)
    0 / 113 (0.00%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    0 / 232 (0.00%)
    0 / 113 (0.00%)
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis
         subjects affected / exposed
    1 / 232 (0.43%)
    0 / 113 (0.00%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Peritoneal adhesions
         subjects affected / exposed
    1 / 232 (0.43%)
    0 / 113 (0.00%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    1 / 232 (0.43%)
    0 / 113 (0.00%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Subileus
         subjects affected / exposed
    1 / 232 (0.43%)
    1 / 113 (0.88%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    3 / 232 (1.29%)
    1 / 113 (0.88%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    0 / 232 (0.00%)
    1 / 113 (0.88%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    1 / 232 (0.43%)
    0 / 113 (0.00%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal failure
         subjects affected / exposed
    1 / 232 (0.43%)
    0 / 113 (0.00%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Abdominal infection
         subjects affected / exposed
    1 / 232 (0.43%)
    0 / 113 (0.00%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    0 / 232 (0.00%)
    0 / 113 (0.00%)
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Colonic abscess
         subjects affected / exposed
    1 / 232 (0.43%)
    0 / 113 (0.00%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cytomegalovirus colitis
         subjects affected / exposed
    1 / 232 (0.43%)
    0 / 113 (0.00%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Device related infection
         subjects affected / exposed
    0 / 232 (0.00%)
    1 / 113 (0.88%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lower respiratory tract infection
         subjects affected / exposed
    1 / 232 (0.43%)
    0 / 113 (0.00%)
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Neutropenic sepsis
         subjects affected / exposed
    1 / 232 (0.43%)
    0 / 113 (0.00%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Osteomyelitis
         subjects affected / exposed
    0 / 232 (0.00%)
    1 / 113 (0.88%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    4 / 232 (1.72%)
    0 / 113 (0.00%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    1 / 232 (0.43%)
    0 / 113 (0.00%)
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    1 / 232 (0.43%)
    0 / 113 (0.00%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    2 / 232 (0.86%)
    1 / 113 (0.88%)
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Cachexia
         subjects affected / exposed
    1 / 232 (0.43%)
    0 / 113 (0.00%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dehydration
         subjects affected / exposed
    2 / 232 (0.86%)
    0 / 113 (0.00%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypoalbuminaemia
         subjects affected / exposed
    0 / 232 (0.00%)
    1 / 113 (0.88%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypomagnesaemia
         subjects affected / exposed
    1 / 232 (0.43%)
    0 / 113 (0.00%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    1 / 232 (0.43%)
    1 / 113 (0.88%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Rucaparib (Treatment Part) Chemotherapy (Treatment Part) Rucaparib (Crossover Part)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    220 / 232 (94.83%)
    105 / 113 (92.92%)
    63 / 74 (85.14%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    8 / 232 (3.45%)
    7 / 113 (6.19%)
    4 / 74 (5.41%)
         occurrences all number
    8
    9
    8
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    64 / 232 (27.59%)
    24 / 113 (21.24%)
    12 / 74 (16.22%)
         occurrences all number
    116
    48
    29
    Fatigue
         subjects affected / exposed
    55 / 232 (23.71%)
    28 / 113 (24.78%)
    15 / 74 (20.27%)
         occurrences all number
    91
    65
    38
    Oedema peripheral
         subjects affected / exposed
    12 / 232 (5.17%)
    8 / 113 (7.08%)
    0 / 74 (0.00%)
         occurrences all number
    14
    15
    0
    Pyrexia
         subjects affected / exposed
    23 / 232 (9.91%)
    7 / 113 (6.19%)
    2 / 74 (2.70%)
         occurrences all number
    26
    9
    2
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    19 / 232 (8.19%)
    9 / 113 (7.96%)
    7 / 74 (9.46%)
         occurrences all number
    24
    10
    11
    Dyspnoea
         subjects affected / exposed
    25 / 232 (10.78%)
    9 / 113 (7.96%)
    6 / 74 (8.11%)
         occurrences all number
    29
    16
    11
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    19 / 232 (8.19%)
    7 / 113 (6.19%)
    3 / 74 (4.05%)
         occurrences all number
    21
    11
    3
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    74 / 232 (31.90%)
    12 / 113 (10.62%)
    29 / 74 (39.19%)
         occurrences all number
    185
    21
    99
    Aspartate aminotransferase increased
         subjects affected / exposed
    72 / 232 (31.03%)
    8 / 113 (7.08%)
    26 / 74 (35.14%)
         occurrences all number
    139
    11
    80
    Blood alkaline phosphatase increased
         subjects affected / exposed
    16 / 232 (6.90%)
    3 / 113 (2.65%)
    9 / 74 (12.16%)
         occurrences all number
    24
    3
    13
    Blood bilirubin increased
         subjects affected / exposed
    20 / 232 (8.62%)
    0 / 113 (0.00%)
    6 / 74 (8.11%)
         occurrences all number
    35
    0
    15
    Blood cholesterol increased
         subjects affected / exposed
    6 / 232 (2.59%)
    6 / 113 (5.31%)
    6 / 74 (8.11%)
         occurrences all number
    12
    15
    9
    Blood creatinine increased
         subjects affected / exposed
    33 / 232 (14.22%)
    9 / 113 (7.96%)
    15 / 74 (20.27%)
         occurrences all number
    76
    20
    27
    Blood urea increased
         subjects affected / exposed
    9 / 232 (3.88%)
    4 / 113 (3.54%)
    5 / 74 (6.76%)
         occurrences all number
    25
    8
    6
    Electrocardiogram QT prolonged
         subjects affected / exposed
    5 / 232 (2.16%)
    6 / 113 (5.31%)
    4 / 74 (5.41%)
         occurrences all number
    14
    21
    12
    Electrocardiogram repolarisation abnormality
         subjects affected / exposed
    3 / 232 (1.29%)
    4 / 113 (3.54%)
    4 / 74 (5.41%)
         occurrences all number
    6
    6
    5
    Neutrophil count decreased
         subjects affected / exposed
    5 / 232 (2.16%)
    7 / 113 (6.19%)
    2 / 74 (2.70%)
         occurrences all number
    8
    17
    2
    Weight decreased
         subjects affected / exposed
    25 / 232 (10.78%)
    3 / 113 (2.65%)
    6 / 74 (8.11%)
         occurrences all number
    36
    3
    6
    Cardiac disorders
    Sinus tachycardia
         subjects affected / exposed
    7 / 232 (3.02%)
    6 / 113 (5.31%)
    3 / 74 (4.05%)
         occurrences all number
    12
    19
    3
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    12 / 232 (5.17%)
    9 / 113 (7.96%)
    2 / 74 (2.70%)
         occurrences all number
    15
    12
    2
    Dysgeusia
         subjects affected / exposed
    39 / 232 (16.81%)
    8 / 113 (7.08%)
    10 / 74 (13.51%)
         occurrences all number
    44
    8
    11
    Headache
         subjects affected / exposed
    17 / 232 (7.33%)
    6 / 113 (5.31%)
    2 / 74 (2.70%)
         occurrences all number
    26
    6
    3
    Neuropathy peripheral
         subjects affected / exposed
    2 / 232 (0.86%)
    16 / 113 (14.16%)
    2 / 74 (2.70%)
         occurrences all number
    2
    19
    2
    Neurotoxicity
         subjects affected / exposed
    1 / 232 (0.43%)
    7 / 113 (6.19%)
    2 / 74 (2.70%)
         occurrences all number
    1
    11
    7
    Paraesthesia
         subjects affected / exposed
    4 / 232 (1.72%)
    11 / 113 (9.73%)
    1 / 74 (1.35%)
         occurrences all number
    5
    26
    1
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    123 / 232 (53.02%)
    35 / 113 (30.97%)
    30 / 74 (40.54%)
         occurrences all number
    359
    103
    122
    Leukopenia
         subjects affected / exposed
    21 / 232 (9.05%)
    18 / 113 (15.93%)
    30 / 74 (40.54%)
         occurrences all number
    48
    65
    122
    Lymphopenia
         subjects affected / exposed
    7 / 232 (3.02%)
    7 / 113 (6.19%)
    3 / 74 (4.05%)
         occurrences all number
    20
    18
    8
    Neutropenia
         subjects affected / exposed
    47 / 232 (20.26%)
    28 / 113 (24.78%)
    7 / 74 (9.46%)
         occurrences all number
    112
    129
    24
    Thrombocytopenia
         subjects affected / exposed
    46 / 232 (19.83%)
    13 / 113 (11.50%)
    10 / 74 (13.51%)
         occurrences all number
    116
    30
    27
    Gastrointestinal disorders
    Abdominal distension
         subjects affected / exposed
    14 / 232 (6.03%)
    4 / 113 (3.54%)
    4 / 74 (5.41%)
         occurrences all number
    17
    4
    4
    Abdominal pain
         subjects affected / exposed
    54 / 232 (23.28%)
    18 / 113 (15.93%)
    13 / 74 (17.57%)
         occurrences all number
    95
    24
    26
    Abdominal pain lower
         subjects affected / exposed
    12 / 232 (5.17%)
    2 / 113 (1.77%)
    3 / 74 (4.05%)
         occurrences all number
    17
    2
    4
    Abdominal pain upper
         subjects affected / exposed
    20 / 232 (8.62%)
    5 / 113 (4.42%)
    8 / 74 (10.81%)
         occurrences all number
    23
    7
    10
    Ascites
         subjects affected / exposed
    13 / 232 (5.60%)
    2 / 113 (1.77%)
    2 / 74 (2.70%)
         occurrences all number
    27
    4
    2
    Constipation
         subjects affected / exposed
    37 / 232 (15.95%)
    19 / 113 (16.81%)
    14 / 74 (18.92%)
         occurrences all number
    58
    28
    20
    Diarrhoea
         subjects affected / exposed
    47 / 232 (20.26%)
    24 / 113 (21.24%)
    12 / 74 (16.22%)
         occurrences all number
    66
    35
    19
    Dyspepsia
         subjects affected / exposed
    19 / 232 (8.19%)
    7 / 113 (6.19%)
    2 / 74 (2.70%)
         occurrences all number
    24
    10
    3
    Intestinal obstruction
         subjects affected / exposed
    10 / 232 (4.31%)
    0 / 113 (0.00%)
    6 / 74 (8.11%)
         occurrences all number
    12
    0
    8
    Nausea
         subjects affected / exposed
    124 / 232 (53.45%)
    36 / 113 (31.86%)
    31 / 74 (41.89%)
         occurrences all number
    240
    95
    72
    Stomatitis
         subjects affected / exposed
    11 / 232 (4.74%)
    7 / 113 (6.19%)
    3 / 74 (4.05%)
         occurrences all number
    11
    13
    4
    Vomiting
         subjects affected / exposed
    79 / 232 (34.05%)
    19 / 113 (16.81%)
    17 / 74 (22.97%)
         occurrences all number
    159
    33
    37
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    12 / 232 (5.17%)
    38 / 113 (33.63%)
    2 / 74 (2.70%)
         occurrences all number
    12
    49
    2
    Erythema
         subjects affected / exposed
    5 / 232 (2.16%)
    2 / 113 (1.77%)
    7 / 74 (9.46%)
         occurrences all number
    6
    4
    9
    Photosensitivity reaction
         subjects affected / exposed
    10 / 232 (4.31%)
    0 / 113 (0.00%)
    5 / 74 (6.76%)
         occurrences all number
    12
    0
    6
    Pruritus
         subjects affected / exposed
    9 / 232 (3.88%)
    3 / 113 (2.65%)
    7 / 74 (9.46%)
         occurrences all number
    11
    4
    10
    Rash
         subjects affected / exposed
    12 / 232 (5.17%)
    4 / 113 (3.54%)
    4 / 74 (5.41%)
         occurrences all number
    13
    6
    4
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    14 / 232 (6.03%)
    9 / 113 (7.96%)
    5 / 74 (6.76%)
         occurrences all number
    16
    13
    6
    Back pain
         subjects affected / exposed
    12 / 232 (5.17%)
    5 / 113 (4.42%)
    9 / 74 (12.16%)
         occurrences all number
    13
    5
    14
    Pain in extremity
         subjects affected / exposed
    8 / 232 (3.45%)
    5 / 113 (4.42%)
    4 / 74 (5.41%)
         occurrences all number
    8
    9
    8
    Infections and infestations
    Upper respiratory tract infection
         subjects affected / exposed
    8 / 232 (3.45%)
    3 / 113 (2.65%)
    5 / 74 (6.76%)
         occurrences all number
    8
    3
    8
    Urinary tract infection
         subjects affected / exposed
    16 / 232 (6.90%)
    5 / 113 (4.42%)
    5 / 74 (6.76%)
         occurrences all number
    20
    6
    5
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    44 / 232 (18.97%)
    20 / 113 (17.70%)
    19 / 74 (25.68%)
         occurrences all number
    65
    39
    31
    Hypercholesterolaemia
         subjects affected / exposed
    9 / 232 (3.88%)
    5 / 113 (4.42%)
    5 / 74 (6.76%)
         occurrences all number
    18
    7
    6
    Hyperglycaemia
         subjects affected / exposed
    16 / 232 (6.90%)
    15 / 113 (13.27%)
    4 / 74 (5.41%)
         occurrences all number
    32
    40
    4
    Hypertriglyceridaemia
         subjects affected / exposed
    8 / 232 (3.45%)
    7 / 113 (6.19%)
    5 / 74 (6.76%)
         occurrences all number
    23
    11
    12
    Hypomagnesaemia
         subjects affected / exposed
    14 / 232 (6.03%)
    2 / 113 (1.77%)
    2 / 74 (2.70%)
         occurrences all number
    28
    6
    3

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    11 Jan 2018
    Significant changes included in this amendment are summarized as follows: • Updated and consolidated the rucaparib background and safety information based on analyses of other Clovis Oncology studies in patients with ovarian cancer, including information on photosensitivity. • Updated the in vitro and in vivo rucaparib PK and drug-drug interaction (DDI) data based on results from rucaparib clinical studies. • Updated the rucaparib dose modification criteria to include additional guidance specific to suspected cases of drug-induced liver injury (DILI).
    23 Oct 2020
    Significant changes included in this amendment are summarized as follows: • Updated the AESIs to include pneumonitis and similar events, including management guidance and Clovis Oncology Pharmacovigilance (PV) reporting and follow-up requirements to align with the rucaparib IB. • Included guidance for management of anemia for consistency with the rucaparib IB.

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

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Fri Apr 26 09:34:50 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA