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    Clinical Trial Results:
    A Randomized, Double-Blind, Placebo-Controlled Phase II Trial of Neoadjuvant Carboplatin and Paclitaxel, With or Without Debio 1143 in Patients With Newly Diagnosed Advanced Epithelial Ovarian Cancer.

    Summary
    EudraCT number
    		 2015-005137-42
    Trial protocol
    		 ES   BE   FR   IT  
    Global end of trial date
    03 Jan 2018

    Results information
    Results version number
    		 v1(current)
    This version publication date
    20 Dec 2018
    First version publication date
    20 Dec 2018
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    Debio1143-EOC-203
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Debiopharm International, S.A.
    Sponsor organisation address
    Case postale 5911, Chemin Messidor 5-7, Lausanne, Switzerland, 1002
    Public contact
    Clinical Department, Debiopharm International, 0041 21 3210 111, ClinicalTrials@debiopharm.com
    Scientific contact
    Clinical Department, Debiopharm International, 0041 21 3210 111, ClinicalTrials@debiopharm.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    03 Jan 2018
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    03 Jan 2018
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    To assess the antitumour activity according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria of paclitaxel + carboplatin with or without Debio 1143 at the end of neoadjuvant treatment (prior to interval debulking surgery) in subjects with newly diagnosed epithelial ovarian cancer (EOC).
    Protection of trial subjects
    Written approval of the study protocol and the informed consent was obtained from the independent ethics committee (IEC), prior to initiation of the study. The study was conducted in accordance with local regulations, Good Clinical Practice (GCP), International Council for Harmonisation (ICH) notes for GCP (ICH/CPMP/135/95), and ethical principles that have their origin in the Declaration of Helsinki and its amendments.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    16 Jun 2016
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Spain: 8
    Country: Number of subjects enrolled
    Belgium: 9
    Country: Number of subjects enrolled
    France: 6
    Country: Number of subjects enrolled
    Italy: 12
    Worldwide total number of subjects
    35
    EEA total number of subjects
    35
    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)
    24
    From 65 to 84 years
    11
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 This study was conducted from 16 June 2017 to 03 Jan 2018 in France, Italy, Spain and Belgium.

    Pre-assignment
    Screening details
    		 A total of 46 subjects were screened. Out of 46, 36 subjects were randomised and 35 were treated.

    Period 1
    Period 1 title
    Overall study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Carer, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Debio 1143
    Arm description
    		 Debio 1143 was administered orally at a dose of 200 milligram (mg) once daily on Days 1 to 5 of every 21-day cycle in combination with intravenous (IV) paclitaxel 135 milligram per meter square (mg/m^2) and carboplatin administered on Day 1 of every 21-day cycle for 4 cycles.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Debio 1143
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule, hard
    Routes of administration
    Oral use
    Dosage and administration details
    Debio 1143 was administered orally at a dose of 200 mg once daily on Days 1 to 5 of every 21-day cycle.

    Investigational medicinal product name
    Paclitaxel
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Paclitaxel 135 mg/m^2 was administered intravenously on Day 1 of every 21-cycle of 4 cycles.

    Investigational medicinal product name
    Carboplatin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Carboplatin was administered intravenously on Day 1 of every 21-cycle of 4 cycles.

    Arm title
    		 Placebo
    Arm description
    		 Matching placebo to Debio 1143 was administered orally once daily on Days 1 to 5 of every 21-day cycle in combination with standard 3-hour IV paclitaxel 175 mg/m^2 and carboplatin administered on Day 1 of every 21-day cycle for 4 cycles.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule, hard
    Routes of administration
    Oral use
    Dosage and administration details
    Matching placebo to Debio 1143 was administered orally once daily on Days 1 to 5 of every 21-day cycle.

    Investigational medicinal product name
    Paclitaxel
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Paclitaxel 175 mg/m^2 was administered intravenously on Day 1 of every 21-cycle of 4 cycles.

    Investigational medicinal product name
    Carboplatin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Carboplatin was administered intravenously on Day 1 of every 21-cycle of 4 cycles.

    Number of subjects in period 1
    		Debio 1143 Placebo
    Started
    22
    13
    Completed
    18
    13
    Not completed
    4
    0
         Death
    1
    -
         Non-compliance with study drug
    1
    -
         Adverse event
    1
    -
         Progressive disease
    1
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Debio 1143
    Reporting group description
    		 Debio 1143 was administered orally at a dose of 200 milligram (mg) once daily on Days 1 to 5 of every 21-day cycle in combination with intravenous (IV) paclitaxel 135 milligram per meter square (mg/m^2) and carboplatin administered on Day 1 of every 21-day cycle for 4 cycles.

    Reporting group title
    Placebo
    Reporting group description
    		 Matching placebo to Debio 1143 was administered orally once daily on Days 1 to 5 of every 21-day cycle in combination with standard 3-hour IV paclitaxel 175 mg/m^2 and carboplatin administered on Day 1 of every 21-day cycle for 4 cycles.

    Reporting group values
    		 Debio 1143 Placebo Total
    Number of subjects
    		 22 13 35
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 58.91 ( 8.12 ) 59.46 ( 9.88 ) -
    Gender categorical
    Units: Subjects
        Female
    		 22 13 35
        Male
    		 0 0 0

    End points

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    End points reporting groups
    Reporting group title
    Debio 1143
    Reporting group description
    		 Debio 1143 was administered orally at a dose of 200 milligram (mg) once daily on Days 1 to 5 of every 21-day cycle in combination with intravenous (IV) paclitaxel 135 milligram per meter square (mg/m^2) and carboplatin administered on Day 1 of every 21-day cycle for 4 cycles.

    Reporting group title
    Placebo
    Reporting group description
    		 Matching placebo to Debio 1143 was administered orally once daily on Days 1 to 5 of every 21-day cycle in combination with standard 3-hour IV paclitaxel 175 mg/m^2 and carboplatin administered on Day 1 of every 21-day cycle for 4 cycles.

    Subject analysis set title
    Before Surgery: Debio 1143
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    Debio 1143 was administered orally at a dose of 200 mg once daily on Days 1 to 5 of every 21-day cycle in combination with intravenous (IV) paclitaxel 135 mg/m^2 and carboplatin administered on Day 1 of every 21-day cycle for 4 cycles.

    Subject analysis set title
    Before Surgery: Placebo
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    Matching placebo to Debio 1143 was administered orally once daily on Days 1 to 5 of every 21-day cycle in combination with standard 3-hour IV paclitaxel 175 mg/m^2 and carboplatin administered on Day 1 of every 21-day cycle for 4 cycles.

    Subject analysis set title
    After Surgery: Debio 1143
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    Debio 1143 was administered orally at a dose of 200 mg once daily on Days 1 to 5 of every 21-day cycle in combination with intravenous (IV) paclitaxel 135 mg/m^2 and carboplatin administered on Day 1 of every 21-day cycle for 4 cycles.

    Subject analysis set title
    After Surgery: Placebo
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    Matching placebo to Debio 1143 was administered orally once daily on Days 1 to 5 of every 21-day cycle in combination with standard 3-hour IV paclitaxel 175 mg/m^2 and carboplatin administered on Day 1 of every 21-day cycle for 4 cycles.

    Primary: Response Rate (RR) Assessed by Central Independent Radiology Committee (CIRC)

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    End point title
    		 Response Rate (RR) Assessed by Central Independent Radiology Committee (CIRC) [1]
    End point description
    Response rate is estimated by complete or partial response based on RECIST v1.1. According to RECIST v1.1, complete response (CR) is defined as disappearance of all target lesions. Any pathological lymph nodes had to have reduction in short axis to less than (<) 10 millimeter (mm). CR had to be confirmed by repeat assessments performed no less than 28 days after the criteria for response were first met to qualify as CR. Partial response (PR) is defined as at least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameter. PR had to be confirmed by repeat assessments performed no less than 28 days after the criteria for response were first met to qualify as PR. The intent-to-treat (ITT) analysis set included all correctly randomized subjects.
    End point type
    Primary
    End point timeframe
    Cycle 2 (Days 15-21), Cycle 4 (Days 15-21), and at end of study (28 days post surgery); Up to approximately 18 months
    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 statistical analysis was planned to be reported for this endpoint.
    End point values
    		 Debio 1143 Placebo
    Number of subjects analysed
    22
    13
    Units: percentage of subjects
        number (not applicable)
    54.5
    23.1
    No statistical analyses for this end point

    Secondary: Rate of Surgical Complete Resection (sCR)

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    End point title
    		 Rate of Surgical Complete Resection (sCR)
    End point description
    Rate of surgical complete resection is defined as no macroscopic residual tumor at time of interval debulking surgery. The ITT analysis set included all correctly randomized subjects.
    End point type
    Secondary
    End point timeframe
    Cycle 2 (Days 15-21), Cycle 4 (Days 15-21), and at end of study (28 days post surgery); Up to approximately 18 months
    End point values
    		 Debio 1143 Placebo
    Number of subjects analysed
    22
    13
    Units: percentage of subjects
        number (confidence interval 95%)
    88.2 (63.6 to 98.5)
    90.9 (58.7 to 99.8)
    No statistical analyses for this end point

    Secondary: Rate of Radiological Complete Response (CR)

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    End point title
    		 Rate of Radiological Complete Response (CR)
    End point description
    The rate of radiological CR before and after debulking surgery is reported. The ITT analysis set included all correctly randomized subjects. Here, 'n' signifies the total number of subjects analyzed at specific timepoint.
    End point type
    Secondary
    End point timeframe
    Cycle 2 (Days 15-21), Cycle 4 (Days 15-21), end of treatment (28 days) and at end of study (28 days post surgery); Up to approximately 18 months
    End point values
    		 Debio 1143 Placebo
    Number of subjects analysed
    22
    13
    Units: percentage of subjects
    number (confidence interval 95%)
        Before Surgery (n =20, 13)
    0 (0 to 16.8)
    0 (0 to 24.7)
        After Surgery (n =14, 8)
    78.6 (49.2 to 95.3)
    62.5 (24.5 to 91.5)
    No statistical analyses for this end point

    Secondary: Rate of Pathological Complete Response (pCR)

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    End point title
    		 Rate of Pathological Complete Response (pCR)
    End point description
    Rate of pathological response (pCR) is defined as no residual invasive cancer at the time of debulking surgery. The ITT analysis set included all correctly randomized subjects.
    End point type
    Secondary
    End point timeframe
    Cycle 2 (Days 15-21), Cycle 4 (Days 15-21), and at end of study (28 days post surgery); Up to approximately 18 months
    End point values
    		 Debio 1143 Placebo
    Number of subjects analysed
    17 [2]
    11 [3]
    Units: percentage of subjects
        number (confidence interval 95%)
    5.9 (0.1 to 28.7)
    9.1 (0.2 to 41.3)
    Notes
    [2] - Here, "number of subjects analysed" signifies those subjects who were evaluable for this endpoint.
    [3] - Here, "number of subjects analysed" signifies those subjects who were evaluable for this endpoint.
    No statistical analyses for this end point

    Secondary: Response Rate of Radiological Response

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    End point title
    		 Response Rate of Radiological Response
    End point description
    The ITT analysis set included all correctly randomized subjects. Here 'n' signifies total number of subjects analyzed at specific timepoint. Here, 99999 indicates number and 95%confidence interval for Placebo arm as it is not estimable, since number of subjects analysed was 0.
    End point type
    Secondary
    End point timeframe
    Cycle 2, 4 and 6: Day 15, end of treatment (28 days) and at end of study (28 days post surgery); Up to approximately 18 months
    End point values
    		 Debio 1143 Placebo
    Number of subjects analysed
    22
    13
    Units: percentage of subjects
    number (confidence interval 95%)
        Cycle 2 Day 15 (n =20, 13)
    40.0 (19.1 to 63.9)
    38.5 (13.9 to 68.4)
        Cycle 4 Day 15 (n =16, 9)
    75.0 (47.6 to 92.7)
    77.8 (40.0 to 97.2)
        Cycle 6 Day 15 (n =1, 0)
    0.0 (0.0 to 97.5)
    99999 (99999 to 99999)
        End of treatment (n =4, 3)
    50.0 (6.8 to 93.2)
    100.0 (29.2 to 100.0)
        Early Discontinuation (n =15, 9)
    86.7 (59.5 to 98.3)
    88.9 (51.8 to 99.7)
        End of study after Post-surgery treatment (n =3,3)
    100.0 (29.2 to 100.0)
    100.0 (29.2 to 100.0)
    No statistical analyses for this end point

    Secondary: Duration of Surgical Intervention

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    End point title
    		 Duration of Surgical Intervention
    End point description
    End point type
    Secondary
    End point timeframe
    Approximately 28 days
    End point values
    		 Debio 1143 Placebo
    Number of subjects analysed
    0 [4]
    0 [5]
    Units: hours
    Notes
    [4] - Due to premature discontinuation of the study, this endpoint was not analyzed.
    [5] - Due to premature discontinuation of the study, this endpoint was not analyzed.
    No statistical analyses for this end point

    Secondary: Rate of Peri-operative Serious Complications Within the First 28 Days

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    End point title
    		 Rate of Peri-operative Serious Complications Within the First 28 Days
    End point description
    End point type
    Secondary
    End point timeframe
    First 28 days
    End point values
    		 Debio 1143 Placebo
    Number of subjects analysed
    0 [6]
    0 [7]
    Units: percentage of subjects
        number (not applicable)
    Notes
    [6] - Due to premature discontinuation of the study, this endpoint was not analyzed.
    [7] - Due to premature discontinuation of the study, this endpoint was not analyzed.
    No statistical analyses for this end point

    Secondary: Rate of Post-Operative Death [Less Than (<) 28 days]

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    End point title
    		 Rate of Post-Operative Death [Less Than (<) 28 days]
    End point description
    The ITT analysis set included all correctly randomized subjects.
    End point type
    Secondary
    End point timeframe
    Less than 28 days
    End point values
    		 Debio 1143 Placebo
    Number of subjects analysed
    20
    13
    Units: percentage of subjects
        number (not applicable)
    0
    0
    No statistical analyses for this end point

    Secondary: Duration of Hospitalization for Debulking Surgery

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    End point title
    		 Duration of Hospitalization for Debulking Surgery
    End point description
    End point type
    Secondary
    End point timeframe
    From day of surgery to day of discharge (approximately 28 days)
    End point values
    		 Debio 1143 Placebo
    Number of subjects analysed
    0 [8]
    0 [9]
    Units: hours
    Notes
    [8] - Due to premature discontinuation of the study, this endpoint was not analyzed.
    [9] - Due to premature discontinuation of the study, this endpoint was not analyzed.
    No statistical analyses for this end point

    Secondary: Number of Subjects with Adverse Events (AEs) and Serious Adverse Events (SAES)

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    End point title
    		 Number of Subjects with Adverse Events (AEs) and Serious Adverse Events (SAES)
    End point description
    An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; Initial or prolonged in-patient 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 to the end of study that were absent before treatment or that worsened relative to pre-treatment state. AEs and SAEs are assessed by National Cancer Institute Common Terminology Criteria Adverse Events (NCI-CTCAE) v4.03. Safety population included all subjects who received any dose of one of the study drugs.
    End point type
    Secondary
    End point timeframe
    Up to 18 months
    End point values
    		 Before Surgery: Debio 1143 Before Surgery: Placebo After Surgery: Debio 1143 After Surgery: Placebo
    Number of subjects analysed
    22
    13
    22
    13
    Units: subjects
        AEs
    22
    13
    3
    1
        SAEs
    1
    1
    1
    0
    No statistical analyses for this end point

    Secondary: Area Under the Curve From Time Zero Extrapolated to Infinite time (AUCinf) of Debio 1143 and Debio 1143-MET1

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    End point title
    		 Area Under the Curve From Time Zero Extrapolated to Infinite time (AUCinf) of Debio 1143 and Debio 1143-MET1 [10]
    End point description
    Pharmacokinetic (PK) population included all subjects for whom valid PK parameters could be estimated. Here, 99999 indicates geometric mean and geometric co-efficient of variation as it was not estimable, since number of subjects analysed was '0'.
    End point type
    Secondary
    End point timeframe
    Pre-dose, 0.5, 3.5, 6.5-8h Day 1 Cycle 1
    Notes
    [10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint was planned to report data for only Debio 1143 reporting arm.
    End point values
    		 Debio 1143
    Number of subjects analysed
    20
    Units: hour*milligram per Litre (h*mg/L)
    geometric mean (geometric coefficient of variation)
        Debio 1143 (n =20)
    15.97 ( 27.66 )
        Debio 1143-MET1 (n =0)
    99999 ( 99999 )
    No statistical analyses for this end point

    Secondary: Area Under the Curve (AUC) From Time Zero to Time tau (AUC0-tau 24 hour) of Debio 1143 and Debio 1143-MET1

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    End point title
    		 Area Under the Curve (AUC) From Time Zero to Time tau (AUC0-tau 24 hour) of Debio 1143 and Debio 1143-MET1 [11]
    End point description
    PK population included all subjects for whom valid PK parameters could be estimated.
    End point type
    Secondary
    End point timeframe
    Pre-dose, 0.5, 3.5, 6.5-8h Day 1 Cycle 1
    Notes
    [11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint was planned to report data for only Debio 1143 reporting arm.
    End point values
    		 Debio 1143
    Number of subjects analysed
    20
    Units: h*mg/L
    geometric mean (geometric coefficient of variation)
        Debio 1143
    12.70 ( 25.78 )
        Debio 1143-MET1
    10.90 ( 50.54 )
    No statistical analyses for this end point

    Secondary: Metabolite Ratio of Area Under the Curve From Time Zero to Time tau (MR AUCtau 24 hour)

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    End point title
    		 Metabolite Ratio of Area Under the Curve From Time Zero to Time tau (MR AUCtau 24 hour) [12]
    End point description
    PK population included all subjects for whom valid PK parameters could be estimated. Here, 99999 indicates geometric mean and geometric co-efficient of variation as it was not estimable, since number of subjects analysed was '0'.
    End point type
    Secondary
    End point timeframe
    Pre-dose, 0.5, 3.5, 6.5-8h Day 1 Cycle 1
    Notes
    [12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint was planned to report data for only Debio 1143 reporting arm.
    End point values
    		 Debio 1143
    Number of subjects analysed
    20
    Units: Ratio
    geometric mean (geometric coefficient of variation)
        Debio 1143 (n =20)
    0.86 ( 43.66 )
        Debio 1143-MET1 (n =0)
    99999 ( 99999 )
    No statistical analyses for this end point

    Secondary: Maximum Observed Plasma Concentration (Cmax) of Debio 1143 and Debio 1143-MET1

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    End point title
    		 Maximum Observed Plasma Concentration (Cmax) of Debio 1143 and Debio 1143-MET1 [13]
    End point description
    End point type
    Secondary
    End point timeframe
    Pre-dose, 0.5, 3.5, 6.5-8h Day 1 Cycle 1
    Notes
    [13] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint was planned to report data for only Debio 1143 reporting arm.
    End point values
    		 Debio 1143
    Number of subjects analysed
    0 [14]
    Units: nanogram per milliliter (ng/mL)
        geometric mean (geometric coefficient of variation)
    ( )
    Notes
    [14] - Due to change in the planned analysis, data for this endpoint was not analyzed.
    No statistical analyses for this end point

    Secondary: Trough Concentration (Ctrough) of Debio 1143 and Debio 1143-MET1

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    End point title
    		 Trough Concentration (Ctrough) of Debio 1143 and Debio 1143-MET1 [15]
    End point description
    End point type
    Secondary
    End point timeframe
    Pre-dose, 0.5, 3.5, 6.5-8h Day 1 Cycle 1
    Notes
    [15] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint was planned to report data for only Debio 1143 reporting arm.
    End point values
    		 Debio 1143
    Number of subjects analysed
    0 [16]
    Units: microgram per milliliter (mcg/mL)
        geometric mean (geometric coefficient of variation)
    ( )
    Notes
    [16] - Due to change in the planned analysis, data for this endpoint was not analyzed.
    No statistical analyses for this end point

    Secondary: Average Concentration (Cavg) of Debio 1143 and Debio 1143-MET1

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    End point title
    		 Average Concentration (Cavg) of Debio 1143 and Debio 1143-MET1 [17]
    End point description
    End point type
    Secondary
    End point timeframe
    Pre-dose, 0.5, 3.5, 6.5-8h Day 1 Cycle 1
    Notes
    [17] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint was planned to report data for only Debio 1143 reporting arm.
    End point values
    		 Debio 1143
    Number of subjects analysed
    0 [18]
    Units: millilitre (mL)
        geometric mean (geometric coefficient of variation)
    ( )
    Notes
    [18] - Due to change in the planned analysis, data for this endpoint was not analyzed.
    No statistical analyses for this end point

    Secondary: Apparent Clearance (CL/F) of Debio 1143 and Debio 1143-MET1

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    End point title
    		 Apparent Clearance (CL/F) of Debio 1143 and Debio 1143-MET1 [19]
    End point description
    End point type
    Secondary
    End point timeframe
    Pre-dose, 0.5, 3.5, 6.5-8h Day 1 Cycle 1
    Notes
    [19] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint was planned to report data for only Debio 1143 reporting arm.
    End point values
    		 Debio 1143
    Number of subjects analysed
    0 [20]
    Units: Liter per hour (L/h)
        geometric mean (geometric coefficient of variation)
    ( )
    Notes
    [20] - Due to change in the planned analysis, data for this endpoint was not analyzed.
    No statistical analyses for this end point

    Secondary: Volume of Distribution of Debio 1143 and Debio 1143-MET1

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    End point title
    		 Volume of Distribution of Debio 1143 and Debio 1143-MET1 [21]
    End point description
    End point type
    Secondary
    End point timeframe
    Pre-dose, 0.5, 3.5, 6.5-8h Day 1 Cycle 1
    Notes
    [21] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint was planned to report data for only Debio 1143 reporting arm.
    End point values
    		 Debio 1143
    Number of subjects analysed
    0 [22]
    Units: Litre (L)
        geometric mean (geometric coefficient of variation)
    ( )
    Notes
    [22] - Due to change in the planned analysis, data for this endpoint was not analyzed.
    No statistical analyses for this end point

    Secondary: Apparent Terminal Elimination Half-Life (t1/2) of Debio 1143 and Debio 1143-MET1

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    End point title
    		 Apparent Terminal Elimination Half-Life (t1/2) of Debio 1143 and Debio 1143-MET1 [23]
    End point description
    End point type
    Secondary
    End point timeframe
    Pre-dose, 0.5, 3.5, 6.5-8h Day 1 Cycle 1
    Notes
    [23] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint was planned to report data for only Debio 1143 reporting arm.
    End point values
    		 Debio 1143
    Number of subjects analysed
    0 [24]
    Units: hour
        geometric mean (geometric coefficient of variation)
    ( )
    Notes
    [24] - Due to change in the planned analysis, data for this endpoint was not analyzed.
    No statistical analyses for this end point

    Secondary: Area Under the Curve From Time Zero Extrapolated to Infinite time (AUCinf) of Paclitaxel

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    End point title
    		 Area Under the Curve From Time Zero Extrapolated to Infinite time (AUCinf) of Paclitaxel
    End point description
    PK population included all subjects for whom valid PK parameters could be estimated.
    End point type
    Secondary
    End point timeframe
    Pre-dose, 0.5, 3.5, 6.5-8h Day 1 Cycle 1
    End point values
    		 Debio 1143 Placebo
    Number of subjects analysed
    20
    12
    Units: h*mg/L
        geometric mean (geometric coefficient of variation)
    10.81 ( 26.45 )
    17.23 ( 36.21 )
    No statistical analyses for this end point

    Secondary: Area Under the Curve (AUC) From Time Zero to Time tau (AUC0-tau 24 hour) of Paclitaxel

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    End point title
    		 Area Under the Curve (AUC) From Time Zero to Time tau (AUC0-tau 24 hour) of Paclitaxel
    End point description
    PK population included all subjects for whom valid PK parameters could be estimated.
    End point type
    Secondary
    End point timeframe
    Pre-dose, 0.5, 3.5, 6.5-8h Day 1 Cycle 1
    End point values
    		 Debio 1143 Placebo
    Number of subjects analysed
    20
    12
    Units: h*mg/L
        geometric mean (geometric coefficient of variation)
    9.29 ( 22.32 )
    13.65 ( 34.70 )
    No statistical analyses for this end point

    Secondary: Area Under the Curve (AUC) From Time Zero to Time tau (AUC0-tau 26 hour) of Paclitaxel

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    End point title
    		 Area Under the Curve (AUC) From Time Zero to Time tau (AUC0-tau 26 hour) of Paclitaxel
    End point description
    PK population included all subjects for whom valid PK parameters could be estimated.
    End point type
    Secondary
    End point timeframe
    Pre-dose, 3.5, 6.5-8h Day 1 Cycle 1
    End point values
    		 Debio 1143 Placebo
    Number of subjects analysed
    20
    12
    Units: h*mg/L
        geometric mean (geometric coefficient of variation)
    9.37 ( 22.41 )
    13.75 ( 34.61 )
    No statistical analyses for this end point

    Secondary: Area Under the Curve (AUC) From Time Zero to Time tau (AUC0-tau 31 hour) of Paclitaxel

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    End point title
    		 Area Under the Curve (AUC) From Time Zero to Time tau (AUC0-tau 31 hour) of Paclitaxel
    End point description
    PK population included all subjects for whom valid PK parameters could be estimated.
    End point type
    Secondary
    End point timeframe
    Pre-dose, 3.5, 6.5-8h Day 1 Cycle 1
    End point values
    		 Debio 1143 Placebo
    Number of subjects analysed
    20
    12
    Units: h*mg/L
        geometric mean (geometric coefficient of variation)
    9.52 ( 22.58 )
    13.98 ( 34.38 )
    No statistical analyses for this end point

    Secondary: Tc>0.05 micromoles per Litre (mcgmol/L) for Paclitaxel

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    End point title
    		 Tc>0.05 micromoles per Litre (mcgmol/L) for Paclitaxel
    End point description
    PK population included all subjects for whom valid PK parameters could be estimated.
    End point type
    Secondary
    End point timeframe
    Pre-dose, 3.5, 6.5-8h Day 1 Cycle 1
    End point values
    		 Debio 1143 Placebo
    Number of subjects analysed
    20
    12
    Units: hour
        geometric mean (geometric coefficient of variation)
    24.17 ( 23.34 )
    29.44 ( 48.63 )
    No statistical analyses for this end point

    Secondary: Clearance for Paclitaxel

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    End point title
    		 Clearance for Paclitaxel
    End point description
    PK population included all subjects for whom valid PK parameters could be estimated.
    End point type
    Secondary
    End point timeframe
    Pre-dose, 3.5, 6.5-8h Day 1 Cycle 1
    End point values
    		 Debio 1143 Placebo
    Number of subjects analysed
    20
    12
    Units: Litre per hour (L/h)
        geometric mean (geometric coefficient of variation)
    20.57 ( 26.33 )
    16.84 ( 36.40 )
    No statistical analyses for this end point

    Secondary: Area Under the Curve From Time Zero Extrapolated to Infinite time (AUCinf) of Free Carboplatin

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    End point title
    		 Area Under the Curve From Time Zero Extrapolated to Infinite time (AUCinf) of Free Carboplatin
    End point description
    PK population included all subjects for whom valid PK parameters could be estimated.
    End point type
    Secondary
    End point timeframe
    Pre-dose, 3.5, 6.5-8h Day 1 Cycle 1
    End point values
    		 Debio 1143 Placebo
    Number of subjects analysed
    17 [25]
    11 [26]
    Units: minute*milligram per millilitre
        geometric mean (geometric coefficient of variation)
    4.51 ( 24.71 )
    4.81 ( 23.56 )
    Notes
    [25] - Here "number of subjects analyzed" signifies total number of subjects analyzed for this endpoint.
    [26] - Here "number of subjects analyzed" signifies total number of subjects analyzed for this endpoint.
    No statistical analyses for this end point

    Secondary: Maximum Observed Plasma Concentration (Cmax) of Free Carboplatin

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    End point title
    		 Maximum Observed Plasma Concentration (Cmax) of Free Carboplatin
    End point description
    PK population included all subjects for whom valid PK parameters could be estimated. Here, 'n' signifies total number of subjects analyzed at specific timepoint.
    End point type
    Secondary
    End point timeframe
    Pre-dose, 4, 6.5-8h post-dose Day 1 Cycle 1; Pre-dose, 4h post-dose Day 1 Cycle 2
    End point values
    		 Debio 1143 Placebo
    Number of subjects analysed
    20
    12
    Units: ng/mL
    geometric mean (geometric coefficient of variation)
        Cycle 1 Day 1 (n =20, 12)
    28614.46 ( 29.61 )
    27026.82 ( 20.05 )
        Cycle 2 Day 1 (n =17, 12)
    31396.28 ( 20.58 )
    29989.05 ( 47.28 )
    No statistical analyses for this end point

    Secondary: Time of Maximum Observed Plasma Concentration (tmax) of Free Carboplatin

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    End point title
    		 Time of Maximum Observed Plasma Concentration (tmax) of Free Carboplatin
    End point description
    PK population included all subjects for whom valid PK parameters could be estimated. Here, 'n' signifies total number of subjects analyzed at specific timepoint.
    End point type
    Secondary
    End point timeframe
    Pre-dose, 4, 6.5-8h post-dose Day 1 Cycle 1; Pre-dose, 4h post-dose Day 1 Cycle 2
    End point values
    		 Debio 1143 Placebo
    Number of subjects analysed
    20
    12
    Units: hour
    median (full range (min-max))
        Cycle 1 Day 1 (n =20, 12)
    1.00 (0.42 to 1.33)
    1.01 (0.50 to 1.35)
        Cycle 2 Day 1 (n =17, 12)
    1.00 (0.42 to 1.33)
    1.02 (0.00 to 1.20)
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Up to 18 months
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    19.0
    Reporting groups
    Reporting group title
    Before Surgery: Debio 1143
    Reporting group description
    		 Debio 1143 was administered orally at a dose of 200 mg once daily on Days 1 to 5 of every 21-day cycle in combination with intravenous (IV) paclitaxel 135 milligram per meter square (mg/m^2) and carboplatin administered on Day 1 of every 21-day cycle for 4 cycles.

    Reporting group title
    Before Surgery: Placebo
    Reporting group description
    		 Matching placebo to Debio 1143 was administered orally once daily on Days 1 to 5 of every 21-day cycle in combination with standard 3-hour IV paclitaxel 175 mg/m^2 and carboplatin administered on Day 1 of every 21-day cycle for 4 cycles.

    Reporting group title
    After Surgery: Debio 1143
    Reporting group description
    		 Debio 1143 was administered orally at a dose of 200 mg once daily on Days 1 to 5 of every 21-day cycle in combination with intravenous (IV) paclitaxel 135 milligram per meter square (mg/m^2) and carboplatin administered on Day 1 of every 21-day cycle for 4 cycles.

    Reporting group title
    After Surgery: Placebo
    Reporting group description
    		 Matching placebo to Debio 1143 was administered orally once daily on Days 1 to 5 of every 21-day cycle in combination with standard 3-hour IV paclitaxel 175 mg/m^2 and carboplatin administered on Day 1 of every 21-day cycle for 4 cycles.

    Serious adverse events
    		 Before Surgery: Debio 1143 Before Surgery: Placebo After Surgery: Debio 1143 After Surgery: Placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    1 / 22 (4.55%)
    1 / 13 (7.69%)
    1 / 22 (4.55%)
    0 / 13 (0.00%)
         number of deaths (all causes)
    1
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    General disorders and administration site conditions
    Multiple organ dysfunction syndrome
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 13 (7.69%)
    0 / 22 (0.00%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 13 (0.00%)
    1 / 22 (4.55%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Sepsis
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 Before Surgery: Debio 1143 Before Surgery: Placebo After Surgery: Debio 1143 After Surgery: Placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    22 / 22 (100.00%)
    13 / 13 (100.00%)
    3 / 22 (13.64%)
    1 / 13 (7.69%)
    Vascular disorders
    Embolism
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 13 (0.00%)
    1 / 22 (4.55%)
    0 / 13 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Hot flush
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Hypertension
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 13 (7.69%)
    0 / 22 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Venous thrombosis
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    0
    0
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    6 / 22 (27.27%)
    5 / 13 (38.46%)
    0 / 22 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    8
    7
    0
    0
    Asthenia
         subjects affected / exposed
    5 / 22 (22.73%)
    5 / 13 (38.46%)
    0 / 22 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    6
    8
    0
    0
    Pyrexia
         subjects affected / exposed
    1 / 22 (4.55%)
    2 / 13 (15.38%)
    0 / 22 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    1
    2
    0
    0
    Mucosal inflammation
         subjects affected / exposed
    1 / 22 (4.55%)
    1 / 13 (7.69%)
    0 / 22 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Oedema peripheral
         subjects affected / exposed
    1 / 22 (4.55%)
    1 / 13 (7.69%)
    0 / 22 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Mucosal dryness
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Multiple organ dysfunction syndrome
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Immune system disorders
    Hypersensitivity
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Reproductive system and breast disorders
    Breast pain
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 13 (7.69%)
    0 / 22 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Genital haemorrhage
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 13 (7.69%)
    0 / 22 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    0
    2
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Epistaxis
         subjects affected / exposed
    1 / 22 (4.55%)
    1 / 13 (7.69%)
    0 / 22 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    2
    2
    0
    0
    Dyspnoea
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 13 (0.00%)
    1 / 22 (4.55%)
    0 / 13 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Pulmonary embolism
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    3 / 22 (13.64%)
    1 / 13 (7.69%)
    0 / 22 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    3
    1
    0
    0
    Anxiety
         subjects affected / exposed
    0 / 22 (0.00%)
    2 / 13 (15.38%)
    0 / 22 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    0
    2
    0
    0
    Emotional disorder
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    5 / 22 (22.73%)
    2 / 13 (15.38%)
    0 / 22 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    5
    3
    0
    0
    Aspartate aminotransferase increased
         subjects affected / exposed
    2 / 22 (9.09%)
    1 / 13 (7.69%)
    0 / 22 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    2
    1
    0
    0
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    0 / 22 (0.00%)
    2 / 13 (15.38%)
    0 / 22 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    0
    2
    0
    0
    Weight decreased
         subjects affected / exposed
    0 / 22 (0.00%)
    2 / 13 (15.38%)
    0 / 22 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    0
    2
    0
    0
    Blood alkaline phosphatase increased
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 13 (7.69%)
    0 / 22 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Blood bilirubin increased
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Blood creatinine increased
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Lipase increased
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Neutrophil count decreased
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Platelet count decreased
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 13 (7.69%)
    0 / 22 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    0
    2
    0
    0
    Injury, poisoning and procedural complications
    Procedural pain
         subjects affected / exposed
    4 / 22 (18.18%)
    3 / 13 (23.08%)
    0 / 22 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    4
    3
    0
    0
    Procedural nausea
         subjects affected / exposed
    1 / 22 (4.55%)
    2 / 13 (15.38%)
    0 / 22 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    1
    2
    0
    0
    Infusion related reaction
         subjects affected / exposed
    2 / 22 (9.09%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    4
    0
    0
    0
    Procedural vomiting
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Wound complication
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Cardiac disorders
    Palpitations
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 13 (0.00%)
    1 / 22 (4.55%)
    0 / 13 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Nervous system disorders
    Syncope
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 13 (0.00%)
    1 / 22 (4.55%)
    0 / 13 (0.00%)
         occurrences all number
    0
    0
    2
    0
    Neurotoxicity
         subjects affected / exposed
    4 / 22 (18.18%)
    1 / 13 (7.69%)
    0 / 22 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    6
    3
    0
    0
    Paraesthesia
         subjects affected / exposed
    2 / 22 (9.09%)
    2 / 13 (15.38%)
    0 / 22 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    2
    2
    0
    0
    Peripheral sensory neuropathy
         subjects affected / exposed
    2 / 22 (9.09%)
    2 / 13 (15.38%)
    0 / 22 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    2
    2
    0
    0
    Headache
         subjects affected / exposed
    2 / 22 (9.09%)
    1 / 13 (7.69%)
    0 / 22 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    3
    1
    0
    0
    Neuropathy peripheral
         subjects affected / exposed
    3 / 22 (13.64%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    4
    0
    0
    0
    Burning sensation
         subjects affected / exposed
    2 / 22 (9.09%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Dizziness
         subjects affected / exposed
    2 / 22 (9.09%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Dysaesthesia
         subjects affected / exposed
    1 / 22 (4.55%)
    1 / 13 (7.69%)
    0 / 22 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    1
    2
    0
    0
    Dysgeusia
         subjects affected / exposed
    1 / 22 (4.55%)
    1 / 13 (7.69%)
    0 / 22 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Migraine
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Neuralgia
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 13 (7.69%)
    0 / 22 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Presyncope
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 13 (7.69%)
    0 / 22 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Blood and lymphatic system disorders
    Neutropenia
         subjects affected / exposed
    13 / 22 (59.09%)
    9 / 13 (69.23%)
    0 / 22 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    19
    16
    0
    0
    Anaemia
         subjects affected / exposed
    5 / 22 (22.73%)
    9 / 13 (69.23%)
    0 / 22 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    9
    14
    0
    0
    Leukopenia
         subjects affected / exposed
    4 / 22 (18.18%)
    4 / 13 (30.77%)
    0 / 22 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    8
    6
    0
    0
    Eye disorders
    Vision blurred
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Gastrointestinal disorders
    Constipation
         subjects affected / exposed
    7 / 22 (31.82%)
    8 / 13 (61.54%)
    1 / 22 (4.55%)
    0 / 13 (0.00%)
         occurrences all number
    10
    9
    1
    0
    Nausea
         subjects affected / exposed
    5 / 22 (22.73%)
    8 / 13 (61.54%)
    0 / 22 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    6
    8
    0
    0
    Vomiting
         subjects affected / exposed
    4 / 22 (18.18%)
    6 / 13 (46.15%)
    0 / 22 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    6
    6
    0
    0
    Abdominal pain
         subjects affected / exposed
    1 / 22 (4.55%)
    3 / 13 (23.08%)
    0 / 22 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    1
    6
    0
    0
    Diarrhoea
         subjects affected / exposed
    2 / 22 (9.09%)
    1 / 13 (7.69%)
    1 / 22 (4.55%)
    0 / 13 (0.00%)
         occurrences all number
    2
    1
    1
    0
    Abdominal pain upper
         subjects affected / exposed
    0 / 22 (0.00%)
    2 / 13 (15.38%)
    1 / 22 (4.55%)
    0 / 13 (0.00%)
         occurrences all number
    0
    2
    1
    0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    1 / 22 (4.55%)
    1 / 13 (7.69%)
    0 / 22 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Stomatitis
         subjects affected / exposed
    2 / 22 (9.09%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Encapsulating peritoneal sclerosis
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 13 (7.69%)
    0 / 22 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Haemorrhoids
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Odynophagia
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    7 / 22 (31.82%)
    5 / 13 (38.46%)
    0 / 22 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    7
    7
    0
    0
    Pruritus
         subjects affected / exposed
    1 / 22 (4.55%)
    2 / 13 (15.38%)
    0 / 22 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    1
    2
    0
    0
    Erythema
         subjects affected / exposed
    1 / 22 (4.55%)
    1 / 13 (7.69%)
    0 / 22 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Rash
         subjects affected / exposed
    2 / 22 (9.09%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Dry skin
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 13 (7.69%)
    0 / 22 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Nail disorder
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Rash maculo-papular
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Urticaria
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 13 (7.69%)
    0 / 22 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Renal and urinary disorders
    Urinary tract pain
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    6 / 22 (27.27%)
    4 / 13 (30.77%)
    1 / 22 (4.55%)
    1 / 13 (7.69%)
         occurrences all number
    7
    5
    1
    1
    Myalgia
         subjects affected / exposed
    2 / 22 (9.09%)
    2 / 13 (15.38%)
    1 / 22 (4.55%)
    0 / 13 (0.00%)
         occurrences all number
    4
    2
    1
    0
    Back pain
         subjects affected / exposed
    1 / 22 (4.55%)
    1 / 13 (7.69%)
    1 / 22 (4.55%)
    0 / 13 (0.00%)
         occurrences all number
    1
    1
    1
    0
    Bone pain
         subjects affected / exposed
    1 / 22 (4.55%)
    1 / 13 (7.69%)
    0 / 22 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Groin pain
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Musculoskeletal pain
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Pain in extremity
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 13 (7.69%)
    0 / 22 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Infections and infestations
    Diverticulitis
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Nasopharyngitis
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Respiratory tract infection
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Sepsis
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 13 (0.00%)
    0 / 22 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Urinary tract infection
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 13 (7.69%)
    0 / 22 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    2 / 22 (9.09%)
    2 / 13 (15.38%)
    1 / 22 (4.55%)
    0 / 13 (0.00%)
         occurrences all number
    2
    3
    1
    0
    Hypomagnesaemia
         subjects affected / exposed
    1 / 22 (4.55%)
    1 / 13 (7.69%)
    0 / 22 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    1
    1
    0
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    12 Oct 2016
    1. Clarified, adjusted, and reorganized the objectives. 2. Modified the statistical method for the analysis of the primary endpoint by biomarker category. 3. Adjusted the derived efficacy parameters and efficacy assessments.

    Interruptions (globally)
    Were there any global interruptions to the trial? Yes
    Date
    Interruption
    Restart date
    03 Nov 2017
    Sponsor decided to discontinue the study based on the paclitaxel underexposure observed in the investigational arm (Debio 1143 + paclitaxel 135 mg/m2 + carboplatin) reported by the IDMC members during the PK/safety analysis.
    -

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    Due to the early termination of the study, less number of subjects were randomized.
    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.

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