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    Clinical Trial Results:
    A Phase 2-3 Multicenter, Randomized, Double-blind Study of Selinexor (KPT-330) versus Placebo in Patients with Advanced Unresectable Dedifferentiated Liposarcoma (DDLS)

    Summary
    EudraCT number
    		 2015-003594-14
    Trial protocol
    		 GB   DE   FR   ES   SE   BE   IT  
    Global end of trial date
    26 Oct 2021

    Results information
    Results version number
    		 v1(current)
    This version publication date
    21 Jan 2023
    First version publication date
    21 Jan 2023
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    KCP-330-020
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02606461
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Karyopharm Therapeutics Inc.
    Sponsor organisation address
    85 Wells Avenue, Newton, MA, United States, 02459
    Public contact
    Clinical Trial Information, Karyopharm Therapeutics, Inc., +1 617658 0600, clinicaltrials@karyopharm.com
    Scientific contact
    Clinical Trial Information, Karyopharm Therapeutics, Inc., +1 617658 0600, clinicaltrials@karyopharm.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
    26 Oct 2021
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    26 Oct 2021
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The main objective of the Phase 2 was to assess and compare progression-free Survival (PFS) of subjects with advanced unresectable dedifferentiated Liposarcoma (DDLS) treated with selinexor (60 milligram [mg]) or placebo twice weekly and Phase 3 was to assess and compare PFS of subjects with advanced unresectable DDLS treated with selinexor (60 mg) or placebo twice weekly.
    Protection of trial subjects
    The study was conducted in accordance with the ethical principles originating in the Declaration of Helsinki in place at the time of study conduct. The study was conducted in compliance with the International Council for Harmonisation (ICH) E6 Guideline for Good Clinical Practice (GCP) (Committee for Proprietary Medicinal Products [CPMP] guideline CPMP/ICH/135/95), United States Code of Federal Code of Regulations, and all applicable local regulatory requirements.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    04 Jan 2016
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Canada: 27
    Country: Number of subjects enrolled
    United States: 175
    Country: Number of subjects enrolled
    Israel: 3
    Country: Number of subjects enrolled
    Spain: 34
    Country: Number of subjects enrolled
    Sweden: 3
    Country: Number of subjects enrolled
    United Kingdom: 12
    Country: Number of subjects enrolled
    Belgium: 4
    Country: Number of subjects enrolled
    France: 37
    Country: Number of subjects enrolled
    Germany: 10
    Country: Number of subjects enrolled
    Italy: 37
    Worldwide total number of subjects
    342
    EEA total number of subjects
    125
    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)
    174
    From 65 to 84 years
    168
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 The study was conducted at 71 sites in the United States, Canada, Germany, Belgium, Israel, United Kingdom, France, Spain, Italy, and Sweden. A total of 342 subjects were enrolled, out of which 57 subjects were randomised to receive study treatment in Phase 2 and 285 subjects randomised, of which 284 subjects received study treatment in Phase 3.

    Pre-assignment
    Screening details
    		 This study consisted of 2 Phases (2 and 3), where subjects were randomised to selinexor or placebo in double-blind treatment. Subjects in the placebo group who had progressive disease (PD) during the Phase 2 and 3 double-blinded treatment, could crossover to open-label selinexor treatment.

    Period 1
    Period 1 title
    Period 1: Double-blinded Period
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Phase 2 Double-blinded: selinexor
    Arm description
    		 Subjects received a fixed blinded dose of 60 milligrams (mg) selinexor twice-weekly on Day 1 and 3 during each 6-week (42-day) cycle.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Selinexor
    Investigational medicinal product code
    Other name
    KPT-330
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received a fixed blinded dose of 60 mg Selinexor twice weekly on Day 1 and 3.

    Arm title
    		 Phase 2 Double-blinded: placebo
    Arm description
    		 Subjects received a fixed blinded dose of placebo matched to selinexor twice-weekly on Day 1 and 3 during each 6-week (42-day) cycle.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received a fixed blinded dose of placebo matched to Selinexor twice weekly on Day 1 and 3.

    Arm title
    		 Phase 3 Double-blinded: selinexor
    Arm description
    		 Subjects received a fixed blinded dose of 60 mg selinexor twice-weekly on Day 1 and 3 during each 6-week (42-day) cycle.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Selinexor
    Investigational medicinal product code
    Other name
    KPT-330
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received a fixed blinded dose of 60 mg Selinexor twice weekly on Day 1 and 3.

    Arm title
    		 Phase 3 Double-blinded: placebo
    Arm description
    		 Subjects received a fixed blinded dose of placebo matched to selinexor twice-weekly on Day 1 and 3 during each 6-week (42-day) cycle.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received a fixed blinded dose of placebo matched to Selinexor twice weekly on Day 1 and 3.

    Number of subjects in period 1
    		Phase 2 Double-blinded: selinexor Phase 2 Double-blinded: placebo Phase 3 Double-blinded: selinexor Phase 3 Double-blinded: placebo
    Started
    27
    30
    188
    97
    Completed
    27
    30
    187
    97
    Not completed
    0
    0
    1
    0
         Randomised but no treatment
    -
    -
    1
    -
    Period 2
    Period 2 title
    Period 2: Open Label Period
    Is this the baseline period?
    		 No
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    No

    Arm title
    		 Phase 2: Open Label- selinexor
    Arm description
    		 Subjects in the placebo group who had PD during Phase 2 double-blinded treatment were entered in open label and received selinexor 60 mg tablet twice-weekly during Weeks 1 to 6 of each 6-week (42-day) cycle.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Selinexor
    Investigational medicinal product code
    Other name
    KPT-330
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subject received 60 mg Selinexor tablet twice-weekly during Weeks 1 to 6.

    Arm title
    		 Phase 3: Open Label- selinexor
    Arm description
    		 Subjects in the placebo group who had PD during Phase 3 double-blinded treatment, were entered in open label and received selinexor 60 mg tablet twice-weekly during Weeks 1 to 6 of each 6-week (42-day) cycle.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Selinexor
    Investigational medicinal product code
    Other name
    KPT-330
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subject received 60 mg Selinexor tablet twice-weekly during Weeks 1 to 6.

    Number of subjects in period 2
    		Phase 2: Open Label- selinexor Phase 3: Open Label- selinexor
    Started
    24
    63
    Completed
    24
    63

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Phase 2 Double-blinded: selinexor
    Reporting group description
    		 Subjects received a fixed blinded dose of 60 milligrams (mg) selinexor twice-weekly on Day 1 and 3 during each 6-week (42-day) cycle.

    Reporting group title
    Phase 2 Double-blinded: placebo
    Reporting group description
    		 Subjects received a fixed blinded dose of placebo matched to selinexor twice-weekly on Day 1 and 3 during each 6-week (42-day) cycle.

    Reporting group title
    Phase 3 Double-blinded: selinexor
    Reporting group description
    		 Subjects received a fixed blinded dose of 60 mg selinexor twice-weekly on Day 1 and 3 during each 6-week (42-day) cycle.

    Reporting group title
    Phase 3 Double-blinded: placebo
    Reporting group description
    		 Subjects received a fixed blinded dose of placebo matched to selinexor twice-weekly on Day 1 and 3 during each 6-week (42-day) cycle.

    Reporting group values
    		 Phase 2 Double-blinded: selinexor Phase 2 Double-blinded: placebo Phase 3 Double-blinded: selinexor Phase 3 Double-blinded: placebo Total
    Number of subjects
    		 27 30 188 97 342
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0 0 0
        Newborns (0-27 days)
    		 0 0 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0 0 0
        Children (2-11 years)
    		 0 0 0 0 0
        Adolescents (12-17 years)
    		 0 0 0 0 0
        Adults (18-64 years)
    		 19 17 92 46 174
        From 65-84 years
    		 8 13 96 51 168
        85 years and over
    		 0 0 0 0 0
    Gender categorical
    Units: Subjects
        Female
    		 12 11 74 33 130
        Male
    		 15 19 114 64 212
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    		 2 3 7 6 18
        Not Hispanic or Latino
    		 25 25 149 79 278
        Unknown or Not Reported
    		 0 2 32 12 46
    Race
    Units: Subjects
        American Indian or Alaska Native
    		 0 0 0 0 0
        Asian
    		 2 5 9 3 19
        Native Hawaiian or Other Pacific Islander
    		 1 0 2 0 3
        Black or African American
    		 1 2 3 1 7
        White
    		 23 20 139 80 262
        More than one race
    		 0 3 34 13 50
        Unknown or Not Reported
    		 0 0 1 0 1

    End points

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    End points reporting groups
    Reporting group title
    Phase 2 Double-blinded: selinexor
    Reporting group description
    		 Subjects received a fixed blinded dose of 60 milligrams (mg) selinexor twice-weekly on Day 1 and 3 during each 6-week (42-day) cycle.

    Reporting group title
    Phase 2 Double-blinded: placebo
    Reporting group description
    		 Subjects received a fixed blinded dose of placebo matched to selinexor twice-weekly on Day 1 and 3 during each 6-week (42-day) cycle.

    Reporting group title
    Phase 3 Double-blinded: selinexor
    Reporting group description
    		 Subjects received a fixed blinded dose of 60 mg selinexor twice-weekly on Day 1 and 3 during each 6-week (42-day) cycle.

    Reporting group title
    Phase 3 Double-blinded: placebo
    Reporting group description
    		 Subjects received a fixed blinded dose of placebo matched to selinexor twice-weekly on Day 1 and 3 during each 6-week (42-day) cycle.
    Reporting group title
    Phase 2: Open Label- selinexor
    Reporting group description
    		 Subjects in the placebo group who had PD during Phase 2 double-blinded treatment were entered in open label and received selinexor 60 mg tablet twice-weekly during Weeks 1 to 6 of each 6-week (42-day) cycle.

    Reporting group title
    Phase 3: Open Label- selinexor
    Reporting group description
    		 Subjects in the placebo group who had PD during Phase 3 double-blinded treatment, were entered in open label and received selinexor 60 mg tablet twice-weekly during Weeks 1 to 6 of each 6-week (42-day) cycle.

    Primary: Phase 3 Double Blind: Progression-free Survival (PFS) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1

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    End point title
    		 Phase 3 Double Blind: Progression-free Survival (PFS) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 [1]
    End point description
    PFS was defined as the time from the date of randomisation until the first date of Independent Review Committee (IRC)-confirmed PD per RECIST version 1.1, or death due to any cause. PD was defined as at least a 20% increase in the sum of the longest diameter (SLD), taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. Phase 3 Intent-to-Treat Population (Ph3-ITT) consisted of all subjects randomised to study treatment in Phase 3, regardless of whether or not they received study treatment.
    End point type
    Primary
    End point timeframe
    From the date of randomisation until the first date of disease progression, or death due to any cause whichever occurred first (up to 57 months)
    Notes
    [1] - 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: Data was assessed and reported for the specific phase only.
    End point values
    		 Phase 3 Double-blinded: selinexor Phase 3 Double-blinded: placebo
    Number of subjects analysed
    188
    97
    Units: Months
        median (confidence interval 90%)
    2.83 (2.73 to 4.11)
    2.07 (1.51 to 3.06)
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Phase 3 Double-blinded: selinexor v Phase 3 Double-blinded: placebo
    Number of subjects included in analysis
    285
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0114
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.7026
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.5191
         upper limit
    		 0.9509

    Primary: Phase 3 Open Label: Progression-free Survival (PFS) as Per RECIST Version 1.1

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    End point title
    		 Phase 3 Open Label: Progression-free Survival (PFS) as Per RECIST Version 1.1 [2]
    End point description
    PFS was defined as the time from the date of randomisation in the Phase 3 open-label period until the first date of IRC-confirmed PD per RECIST version 1.1, or death due to any cause. PD was defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. The Phase 3 Open-Label Population (Ph3-OL) consisted of all subjects in Phase 3 who were randomised to placebo in the blinded phase, entered the open-label period, and received at least one dose of open-label selinexor.
    End point type
    Primary
    End point timeframe
    From the date of randomisation in phase 3 open label period until the first date of disease progression, or death due to any cause whichever occurred first (up to 57 months)
    Notes
    [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical testing was performed for the primary end point.
    End point values
    		 Phase 3: Open Label- selinexor
    Number of subjects analysed
    63
    Units: Months
        median (confidence interval 95%)
    2.73 (1.97 to 4.14)
    No statistical analyses for this end point

    Primary: Phase 2 Double Blind: Progression-free Survival (PFS) as Per RECIST Version 1.1

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    End point title
    		 Phase 2 Double Blind: Progression-free Survival (PFS) as Per RECIST Version 1.1 [3]
    End point description
    PFS was defined as the time from date of randomisation until the first date of IRC-confirmed PD per RECIST version 1.1, or death due to any cause. PD was defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. The Phase 2 Intent-to-Treat Population (Ph2-ITT) consisted of all subjects randomised to study treatment in Phase 2, regardless of whether or not they received study treatment. Here '99999' signifies that data could not be estimated due to higher number (>50%) of deaths.
    End point type
    Primary
    End point timeframe
    From date of randomisation until the first date of PD or death due to any cause, whichever occurred first (up to 57 months)
    Notes
    [3] - 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: Data was assessed and reported for the specific phase only.
    End point values
    		 Phase 2 Double-blinded: selinexor Phase 2 Double-blinded: placebo
    Number of subjects analysed
    27
    30
    Units: Months
        median (confidence interval 95%)
    3.02 (1.41 to 99999)
    2.76 (1.58 to 99999)
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Phase 2 Double-blinded: selinexor v Phase 2 Double-blinded: placebo
    Number of subjects included in analysis
    57
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.6051
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.1521
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.5357
         upper limit
    		 2.4778

    Primary: Phase 2 Open Label: Progression-free Survival (PFS) as Per RECIST Version 1.1

    		 Close Top of page
    End point title
    		 Phase 2 Open Label: Progression-free Survival (PFS) as Per RECIST Version 1.1 [4]
    End point description
    PFS was defined as the time from date of randomisation in the Phase 2 open-label period until the first date of IRC-confirmed PD per RECIST version 1.1, or death due to any cause. PD was defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. The Phase 2 Open-Label Population (Ph2-OL) consisted of all subjects in Phase 2 who were randomised to placebo in the blinded phase, entered open-label period, and received at least one dose of open-label selinexor.
    End point type
    Primary
    End point timeframe
    From date of randomisation in the Phase 2 open label period until the first date of PD or death due to any cause, whichever occurred first (up to 57 months)
    Notes
    [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical testing was performed for the primary end point.
    End point values
    		 Phase 2: Open Label- selinexor
    Number of subjects analysed
    24
    Units: Months
        median (confidence interval 95%)
    1.38 (1.38 to 2.27)
    No statistical analyses for this end point

    Secondary: Phase 3 Double Blind: Overall Survival (OS)

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    End point title
    		 Phase 3 Double Blind: Overall Survival (OS) [5]
    End point description
    OS was defined as the duration (in months) from the date of randomisation to death from any cause. Subject last known to be alive were censored at the date of discontinuation from the study, or database cut date, whichever was earlier. The Ph3-ITT consisted of all subjects randomised to study treatment in Phase 3, regardless of whether or not they received study treatment.
    End point type
    Secondary
    End point timeframe
    From date of randomisation until death due to any cause, whichever occurred first (up to 70 months)
    Notes
    [5] - 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: Data was assessed and reported for the specific phase only.
    End point values
    		 Phase 3 Double-blinded: selinexor Phase 3 Double-blinded: placebo
    Number of subjects analysed
    188
    97
    Units: Months
        median (confidence interval 95%)
    10.38 (8.41 to 13.40)
    12.71 (8.54 to 15.90)
    No statistical analyses for this end point

    Secondary: Phase 3 Open Label: Overall Survival (OS)

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    End point title
    		 Phase 3 Open Label: Overall Survival (OS)
    End point description
    OS was defined as the duration (in months) from the date of randomisation in the Phase 3 open-label period to death from any cause. Subjects last known to be alive were censored at the date of discontinuation from the study, or database cut date, whichever was earlier. The Ph3-OL consisted of all Subjects in Phase 3 who were randomised to placebo in the blinded phase, entered the open-label period, and received at least one dose of open-label selinexor.
    End point type
    Secondary
    End point timeframe
    From date of randomisation in phase 3 open label period until death due to any cause, whichever occurred first (up to 70 months)
    End point values
    		 Phase 3: Open Label- selinexor
    Number of subjects analysed
    63
    Units: Months
        median (confidence interval 95%)
    10.18 (5.78 to 14.69)
    No statistical analyses for this end point

    Secondary: Phase 2 Open Label: Overall Survival (OS)

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    End point title
    		 Phase 2 Open Label: Overall Survival (OS)
    End point description
    OS was defined as the duration (in months) from the date of randomisation in the Phase 2 open-label period to death from any cause. Subjects last known to be alive were censored at the date of discontinuation from the study, or database cut date, whichever was earlier. The Ph2-OL consisted of all subjects in Phase 2 who were randomised to placebo in the blinded phase, entered the open-label period, and received at least one dose of open-label selinexor.
    End point type
    Secondary
    End point timeframe
    From date of randomisation in the Phase 2 open-label period until death due to any cause, whichever occurred first (up to 70 months)
    End point values
    		 Phase 2: Open Label- selinexor
    Number of subjects analysed
    24
    Units: Months
        median (confidence interval 95%)
    8.90 (4.96 to 18.92)
    No statistical analyses for this end point

    Secondary: Phase 2 Double Blind: Overall Survival (OS)

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    End point title
    		 Phase 2 Double Blind: Overall Survival (OS) [6]
    End point description
    OS was defined as the duration (in months) from the date of randomisation to death from any cause. Subjects last known to be alive were censored at the date of discontinuation from the study, or database cut date, whichever was earlier. The Ph2-ITT consisted of all subjects randomised to study treatment in Phase 2, regardless of whether or not they received study treatment.
    End point type
    Secondary
    End point timeframe
    From the date of randomisation until death due to any cause, whichever occurred first (up to 70 months)
    Notes
    [6] - 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: Data was assessed and reported for the specific phase only.
    End point values
    		 Phase 2 Double-blinded: selinexor Phase 2 Double-blinded: placebo
    Number of subjects analysed
    27
    30
    Units: Months
        median (confidence interval 95%)
    17.31 (10.51 to 29.57)
    16.07 (8.38 to 23.06)
    No statistical analyses for this end point

    Secondary: Phase 3 Double Blind: Time-to-Progression (TTP) as Per RECIST Version 1.1

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    End point title
    		 Phase 3 Double Blind: Time-to-Progression (TTP) as Per RECIST Version 1.1 [7]
    End point description
    TTP was defined as the time from date of randomisation until ICR determined PD as per RECIST version 1.1, or death due to disease progression, whichever occurred first. PD was defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. The Ph3-ITT consisted of all subjects randomised to study treatment in Phase 3, regardless of whether or not they received study treatment.
    End point type
    Secondary
    End point timeframe
    From date of randomisation until the first date of PD or death due to any cause, whichever occurred first (up to 70 months)
    Notes
    [7] - 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: Data was assessed and reported for the specific phase only.
    End point values
    		 Phase 3 Double-blinded: selinexor Phase 3 Double-blinded: placebo
    Number of subjects analysed
    188
    97
    Units: Months
        median (confidence interval 95%)
    2.83 (2.73 to 4.11)
    2.10 (1.51 to 3.06)
    No statistical analyses for this end point

    Secondary: Phase 3 Open Label: Time-to-Progression (TTP) as Per RECIST Version 1.1

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    End point title
    		 Phase 3 Open Label: Time-to-Progression (TTP) as Per RECIST Version 1.1
    End point description
    TTP was defined as the time from date of randomization in the Phase 3 open-label period until ICR-determined PD per RECIST version 1.1, or death due to disease progression, whichever occurred first. PD was defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. The Ph3-OL consisted of all subjects in Phase 3 who were randomised to placebo in the blinded phase, entered the open-label period and received at least one dose of open-label selinexor.
    End point type
    Secondary
    End point timeframe
    From date of randomisation in the Phase 3 open label-period until the first date of PD or death due to any cause, whichever occurred first (up to 70 months)
    End point values
    		 Phase 3: Open Label- selinexor
    Number of subjects analysed
    63
    Units: Months
        median (confidence interval 95%)
    2.73 (1.97 to 4.14)
    No statistical analyses for this end point

    Secondary: Phase 2 Double Blind: Time-to-Progression (TTP) as Per RECIST Version 1.1

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    End point title
    		 Phase 2 Double Blind: Time-to-Progression (TTP) as Per RECIST Version 1.1 [8]
    End point description
    TTP was defined as the time from date of randomisation until ICR-determined PD as per RECIST version 1.1, or death due to disease progression, whichever occurred first. PD was defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. The Ph2-ITT consisted of all subjects randomised to study treatment in Phase 2, regardless of whether or not they received study treatment. Here '99999' signifies that data could not be estimated due to the higher number (>50%) of deaths.
    End point type
    Secondary
    End point timeframe
    From date of randomisation until the first date of PD or death due to any cause, whichever occurred first (up to 70 months)
    Notes
    [8] - 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: Data was assessed and reported for the specific phase only.
    End point values
    		 Phase 2 Double-blinded: selinexor Phase 2 Double-blinded: placebo
    Number of subjects analysed
    27
    30
    Units: Months
        median (confidence interval 95%)
    3.02 (1.41 to 99999)
    2.76 (1.58 to 99999)
    No statistical analyses for this end point

    Secondary: Phase 3 Double Blind: Overall Response Rate (ORR)

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    End point title
    		 Phase 3 Double Blind: Overall Response Rate (ORR) [9]
    End point description
    ORR was defined as the percentage of subjects who achieved complete response (CR) or partial response (PR), per RECIST v.1.1. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. The Ph3-ITT consisted of all subjects randomised to study treatment in Phase 3, regardless of whether or not they received study treatment. Here '99999' signifies that data could not be evaluated due to no events of CR and PR in placebo arm.
    End point type
    Secondary
    End point timeframe
    From date of randomisation until the documentation of CR or PR (up to 70 months)
    Notes
    [9] - 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: Data was assessed and reported for the specific phase only.
    End point values
    		 Phase 3 Double-blinded: selinexor Phase 3 Double-blinded: placebo
    Number of subjects analysed
    188
    97
    Units: Percentage of subjects
        number (confidence interval 95%)
    2.7 (0.9 to 6.1)
    99999 (99999 to 99999)
    No statistical analyses for this end point

    Secondary: Phase 2 Open Label: Time-to-Progression (TTP) as Per RECIST Version 1.1

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    End point title
    		 Phase 2 Open Label: Time-to-Progression (TTP) as Per RECIST Version 1.1
    End point description
    TTP was defined as the time from date of randomisation in the Phase 2 open-label period until ICR-determined PD per RECIST version 1.1, or death due to disease progression, whichever occurred first. PD was defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. The Ph2-OL consisted of all subjects in Phase 2 who were randomised to placebo in the blinded phase, entered the open-label period and received at least one dose of open-label selinexor.
    End point type
    Secondary
    End point timeframe
    From date of randomisation in the Phase 2 open-label period until the first date of PD or death due to any cause, whichever occurred first (up to 70 months)
    End point values
    		 Phase 2: Open Label- selinexor
    Number of subjects analysed
    24
    Units: Months
        median (confidence interval 95%)
    1.38 (1.38 to 2.27)
    No statistical analyses for this end point

    Secondary: Phase 2 Double Blind: Overall Response Rate (ORR)

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    End point title
    		 Phase 2 Double Blind: Overall Response Rate (ORR) [10]
    End point description
    ORR was defined as the percentage of subjects who achieved CR or PR, per RECIST v.1.1. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. The Ph2-ITT consisted of all subjects randomised to study treatment in Phase 2, regardless of whether or not they received study treatment. Here '99999' signifies that data could not be evaluated since no subjects had CR or PR.
    End point type
    Secondary
    End point timeframe
    From date of randomisation until the documentation of CR or PR (up to 70 months)
    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: Data was assessed and reported for the specific phase only.
    End point values
    		 Phase 2 Double-blinded: selinexor Phase 2 Double-blinded: placebo
    Number of subjects analysed
    27
    30
    Units: Percentage of subjects
        number (confidence interval 95%)
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    No statistical analyses for this end point

    Secondary: Phase 3 Open Label: Overall Response Rate (ORR)

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    End point title
    		 Phase 3 Open Label: Overall Response Rate (ORR)
    End point description
    ORR was defined as the percentage of subjects who achieved CR or PR, per RECIST v.1.1. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. The Ph3-OL consisted of all subjects in Phase 3 who were randomised to placebo in blinded phase, entered open-label period and received at least one dose of open-label selinexor.
    End point type
    Secondary
    End point timeframe
    From date of randomisation in phase 3 open label period until the documentation of CR or PR (up to 70 months)
    End point values
    		 Phase 3: Open Label- selinexor
    Number of subjects analysed
    63
    Units: Percentage of subjects
        number (confidence interval 95%)
    3.2 (0.4 to 11)
    No statistical analyses for this end point

    Secondary: Phase 2 Open Label: Overall Response Rate (ORR)

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    End point title
    		 Phase 2 Open Label: Overall Response Rate (ORR)
    End point description
    ORR was defined as the percentage of subjects who achieved CR or PR, per RECIST v.1.1. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. The Ph2-OL consisted of all subjects in Phase 2 who were randomised to placebo in the blinded phase, entered the open-label period and received at least one dose of open-label selinexor. Data could not be evaluated due to no CR or PR events.
    End point type
    Secondary
    End point timeframe
    From date of randomisation in the Phase 2 open label period until the documentation of CR or PR (up to 70 months)
    End point values
    		 Phase 2: Open Label- selinexor
    Number of subjects analysed
    24
    Units: percentage of subjects
    number (not applicable)
        Subjects who achieved CR
    0
        Subjects who achieved PR
    0
    No statistical analyses for this end point

    Secondary: Phase 3 Double Blind: Duration of Response (DOR)

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    End point title
    		 Phase 3 Double Blind: Duration of Response (DOR) [11]
    End point description
    DOR was defined as the time from first occurrence of CR or PR until the first date of PD per RECIST version 1.1 or death. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. PD was defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. Ph3-ITTSet. Here, 'number of subjects analysed” signifies those who had CR and PR in specified group/arm and phase. Here, '99999 and 00000' signifies that upper and lower limit of 95% CI was not estimable due to lesser number of subjects with events.
    End point type
    Secondary
    End point timeframe
    From first occurrence of CR or PR until the first date of PD (up to 70 months)
    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: Data was assessed and reported for the specific phase only.
    End point values
    		 Phase 3 Double-blinded: selinexor Phase 3 Double-blinded: placebo
    Number of subjects analysed
    5
    0 [12]
    Units: Months
        number (confidence interval 95%)
    7.39 (00000 to 99999)
    ( to )
    Notes
    [12] - Data could not be evaluated due to no events of CR and PR.
    No statistical analyses for this end point

    Secondary: Phase 3 Double Blind: Progression-free Survival (PFS) as Per Investigator Assessment

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    End point title
    		 Phase 3 Double Blind: Progression-free Survival (PFS) as Per Investigator Assessment [13]
    End point description
    PFS was defined as the time from date of randomisation until the first date of PD, per RECIST version 1.1, or death due to any cause as defined by the Investigator based on clinical and/or radiologic criteria. PD was defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. The Ph3-ITT consisted of all subjects randomised to study treatment in Phase 3, regardless of whether or not they received study treatment.
    End point type
    Secondary
    End point timeframe
    From the date of randomisation until the first date of disease progression, or death due to any cause, whichever occurred first (up to 70 months)
    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: Data was assessed and reported for the specific phase only.
    End point values
    		 Phase 3 Double-blinded: selinexor Phase 3 Double-blinded: placebo
    Number of subjects analysed
    188
    97
    Units: Months
        median (confidence interval 95%)
    2.89 (2.76 to 4.17)
    1.87 (1.45 to 2.89)
    No statistical analyses for this end point

    Secondary: Phase 3 Double Blind: Time to Next Treatment (TTNT)

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    End point title
    		 Phase 3 Double Blind: Time to Next Treatment (TTNT) [14]
    End point description
    TTNT was defined as time since randomisation until the first new antineoplastic therapy or death due to any cause, whichever occurs first. The Ph3-ITT consisted of all subjects randomised to study treatment in Phase 3, regardless of whether or not they received study treatment.
    End point type
    Secondary
    End point timeframe
    Time from randomisation to the first new antineoplastic therapy or death due to any cause (up to 70 months)
    Notes
    [14] - 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: Data was assessed and reported for the specific phase only.
    End point values
    		 Phase 3 Double-blinded: selinexor Phase 3 Double-blinded: placebo
    Number of subjects analysed
    188
    97
    Units: Months
        median (confidence interval 95%)
    5.42 (4.67 to 6.34)
    3.22 (2.56 to 3.78)
    No statistical analyses for this end point

    Secondary: Phase 2 Double Blind: Time to Next Treatment (TTNT)

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    End point title
    		 Phase 2 Double Blind: Time to Next Treatment (TTNT) [15]
    End point description
    TTNT was defined as time since randomisation until the first new antineoplastic therapy or death due to any cause, whichever occurs first. The Ph2-ITT consisted of all subjects randomised to study treatment in Phase 2, regardless of whether or not they received study treatment.
    End point type
    Secondary
    End point timeframe
    Time from randomisation to the first new antineoplastic therapy or death due to any cause (up to 70 months)
    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: Data was assessed and reported for the specific phase only.
    End point values
    		 Phase 2 Double-blinded: selinexor Phase 2 Double-blinded: placebo
    Number of subjects analysed
    27
    30
    Units: Months
        median (confidence interval 95%)
    4.96 (3.91 to 14.03)
    2.92 (2.04 to 5.06)
    No statistical analyses for this end point

    Secondary: Phase 3 Double Blind: Number of Subjects with Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs

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    End point title
    		 Phase 3 Double Blind: Number of Subjects with Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs [16]
    End point description
    An adverse events was defined as any untoward medical occurrence in a subject or clinical investigation subject administered a pharmaceutical product or placebo and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of study treatment, whether or not considered related to the study treatment. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAEs were defined as those AEs that develop or worsen after the first dose of study drug. TEAEs included both serious and non-serious TEAEs. Phase 3 Safety Population (Ph3-SAF) was included.
    End point type
    Secondary
    End point timeframe
    From start of study drug administration up to 70 months
    Notes
    [16] - 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: Data was assessed and reported for the specific phase only.
    End point values
    		 Phase 3 Double-blinded: selinexor Phase 3 Double-blinded: placebo
    Number of subjects analysed
    187
    97
    Units: subjects
        Subjects with TEAEs
    187
    94
        Subjects with Serious TEAEs
    73
    18
    No statistical analyses for this end point

    Secondary: Phase 3 Open Label: Number of Subjects with TEAEs and Serious TEAEs

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    End point title
    		 Phase 3 Open Label: Number of Subjects with TEAEs and Serious TEAEs
    End point description
    A adverse events was defined as any untoward medical occurrence in a subject or clinical investigation subject administered a pharmaceutical product or placebo and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of study treatment, whether or not considered related to the study treatment. A SAE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAEs were defined as those AEs that develop or worsen after the first dose of study drug. TEAEs included both serious and non-serious TEAEs. Ph3-OL Population was included.
    End point type
    Secondary
    End point timeframe
    From start of study drug administration up to 70 months
    End point values
    		 Phase 3: Open Label- selinexor
    Number of subjects analysed
    63
    Units: Subjects
        Subjects with TEAEs
    63
        Subjects with Serious TEAEs
    25
    No statistical analyses for this end point

    Secondary: Phase 2 Double Blind: Number of Subjects with TEAEs and Serious TEAEs

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    End point title
    		 Phase 2 Double Blind: Number of Subjects with TEAEs and Serious TEAEs [17]
    End point description
    A adverse events was defined as any untoward medical occurrence in a subject or clinical investigation subject administered a pharmaceutical product or placebo and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of study treatment, whether or not considered related to the study treatment. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAEs were defined as those AEs that develop or worsen after the first dose of study drug. TEAEs included both serious and non-serious TEAEs. Phase 2 Safety Population was included.
    End point type
    Secondary
    End point timeframe
    From start of study drug administration up to 70 months
    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: Data was assessed and reported for the specific phase only.
    End point values
    		 Phase 2 Double-blinded: selinexor Phase 2 Double-blinded: placebo
    Number of subjects analysed
    27
    30
    Units: Subjects
        Subject with TEAEs
    27
    29
        Subjects with Serious TEAEs
    4
    6
    No statistical analyses for this end point

    Secondary: Phase 2 Open Label: Number of Subjects with TEAEs and Serious TEAEs

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    End point title
    		 Phase 2 Open Label: Number of Subjects with TEAEs and Serious TEAEs
    End point description
    A adverse events was defined as any untoward medical occurrence in a subject or clinical investigation subject administered a pharmaceutical product or placebo and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of study treatment, whether or not considered related to the study treatment. A SAE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAEs were defined as those AEs that develop or worsen after the first dose of study drug. TEAEs included both serious and non-serious TEAEs. Ph2-OL population was included.
    End point type
    Secondary
    End point timeframe
    From start of study drug administration up to 70 Months
    End point values
    		 Phase 2: Open Label- selinexor
    Number of subjects analysed
    24
    Units: Subjects
        Subjects with TEAEs
    24
        Subjects with Serious TEAEs
    13
    No statistical analyses for this end point

    Secondary: Phase 3 Double Blind: Change from Baseline in Quality-of-life Questionnaire 30 Item (QLQ-C30)

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    End point title
    		 Phase 3 Double Blind: Change from Baseline in Quality-of-life Questionnaire 30 Item (QLQ-C30) [18]
    End point description
    TQLQ-C30 was 30-item questionnaire developed to assess quality of life of patients with cancer. QLQ-C30 contains 30 questions that include five functional scales (physical, role, emotional, social, and cognitive functioning); three symptom scales (fatigue, nausea/vomiting and pain), six single-item symptom items (dyspnea, insomnia, appetite loss, constipation, diarrhea, financial difficulties) and global health status/quality of life (QoL). Most questions used 4-point scale (1 ‘Not at all’ to 4 ‘Very much’; 2 questions used 7-point scale (1 ‘very poor’ to 7 ‘Excellent’). Scores averaged, transformed to 0-100 scale; for functional scales and global health status/QoL, a higher score = better level of functioning (better health status); for symptom scales/items, a higher score = higher level of symptomatology/problems (worse health status). Ph3-ITT. "Overall Subjects analysed"=subjects evaluable for this endpoint. '99999'=standard deviation was not estimated due to single subject.
    End point type
    Secondary
    End point timeframe
    Baseline up to Day 1387
    Notes
    [18] - 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: Data was assessed and reported for the specific phase only.
    End point values
    		 Phase 3 Double-blinded: selinexor Phase 3 Double-blinded: placebo
    Number of subjects analysed
    1
    0 [19]
    Units: Score on a Scale
    arithmetic mean (standard deviation)
        Global health status
    33.33 ( 99999 )
    ( )
        Physical Functioning
    20.0 ( 99999 )
    ( )
        Role Functioning
    16.67 ( 99999 )
    ( )
        Emotional Functioning
    8.33 ( 99999 )
    ( )
        Social Functioning
    50.0 ( 99999 )
    ( )
        Cognitive Functioning
    0.00 ( 99999 )
    ( )
        Fatigue
    -22.22 ( 99999 )
    ( )
        Nausea and Vomiting
    16.67 ( 99999 )
    ( )
        Pain
    0.0 ( 99999 )
    ( )
        Dyspnoea
    0.0 ( 99999 )
    ( )
        Insomnia
    33.33 ( 99999 )
    ( )
        Appetite Loss
    0.0 ( 99999 )
    ( )
        Constipation
    0.0 ( 99999 )
    ( )
        Diarrhoea
    33.33 ( 99999 )
    ( )
        Financial Difficulties
    -66.67 ( 99999 )
    ( )
    Notes
    [19] - Zero Subjects were assessed for Placebo arm.
    No statistical analyses for this end point

    Secondary: Phase 3 Open Label: Change from Baseline in Quality-of-life Questionnaire 30 Item (QLQ-C30)

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    End point title
    		 Phase 3 Open Label: Change from Baseline in Quality-of-life Questionnaire 30 Item (QLQ-C30)
    End point description
    TQLQ-C30 was 30-item questionnaire developed to assess quality of life of patients with cancer. QLQ-C30 contains 30 questions that include five functional scales (physical, role, emotional, social, and cognitive functioning); three symptom scales (fatigue, nausea/vomiting and pain), six single-item symptom items (dyspnea, insomnia, appetite loss, constipation, diarrhea, financial difficulties) and global health status/quality of life (QoL). Most questions used 4-point scale (1 ‘Not at all’ to 4 ‘Very much’; 2 questions used 7-point scale (1 ‘very poor’ to 7 ‘Excellent’). Scores averaged, transformed to 0-100 scale; for functional scales and global health status/QoL, a higher score = better level of functioning (better health status); for symptom scales/items, a higher score = higher level of symptomatology/problems (worse health status). Ph3-ITT. "Overall Subjects analysed"=subjects evaluable for this endpoint. '99999'=standard deviation was not estimated due to single subject.
    End point type
    Secondary
    End point timeframe
    Baseline up to Day 379
    End point values
    		 Phase 3: Open Label- selinexor
    Number of subjects analysed
    1
    Units: Score on a Scale
    arithmetic mean (standard deviation)
        Global health status
    -16.67 ( 99999 )
        Physical Functioning
    -40.00 ( 99999 )
        Role Functioning
    -33.33 ( 99999 )
        Emotional Functioning
    0.0 ( 99999 )
        Social Functioning
    -50.0 ( 99999 )
        Cognitive Functioning
    -16.67 ( 99999 )
        Fatigue
    66.67 ( 99999 )
        Nausea and Vomiting
    0.0 ( 99999 )
        Pain
    0.0 ( 99999 )
        Dyspnoea
    0.0 ( 99999 )
        Insomnia
    0.0 ( 99999 )
        Appetite Loss
    0.0 ( 99999 )
        Constipation
    0.0 ( 99999 )
        Diarrhoea
    0.0 ( 99999 )
        Financial Difficulties
    100.0 ( 99999 )
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From start of study drug administration up to 70 months
    Adverse event reporting additional description
    The Ph2-SAF and Ph3-SA consisted of all subjects who had received at least one dose of blinded study treatment in Phase 2 and Phase 3 respectively. The Phase 3 open-label population (Ph3-OL) and Phase 2 open-label Population (Ph2-OL) consisted of all subjects in Phase 3 and Phase 2 respectively, who were randomised to placebo in the blinded.
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    23.0
    Reporting groups
    Reporting group title
    Phase 2 Double-blinded: selinexor
    Reporting group description
    		 Subjects received a fixed blinding dose of 60 mg selinexor twice-weekly on Day 1 and 3 during each 6-week (42-day) cycle.

    Reporting group title
    Phase 2 Double-blinded: placebo
    Reporting group description
    		 Subjects received a fixed blinding dose of placebo matched to selinexor twice-weekly on Day 1 and 3 during each 6-week (42-day) cycle.

    Reporting group title
    Phase 2 Open-label: selinexor
    Reporting group description
    		 Subjects in the placebo group who had PD during Phase 2 double-blinded treatment were entered in open-label and received selinexor 60 mg tablet twice-weekly during Weeks 1 to 6 of each 6-week (42-day) cycle.

    Reporting group title
    Phase 3 Double-blinded: placebo
    Reporting group description
    		 Subjects received a fixed blinding dose of placebo matched to selinexor twice-weekly on Day 1 and 3 during each 6-week (42-day) cycle.

    Reporting group title
    Phase 3 Open-label: selinexor
    Reporting group description
    		 Subjects in the placebo group who had PD during Phase 3 double-blinded treatment, were entered in open-label and received selinexor 60 mg tablet twice-weekly during Weeks 1 to 6 of each 6-week (42-day) cycle.

    Reporting group title
    Phase 3 Double-blinded: selinexor
    Reporting group description
    		 Subjects received a fixed blinding dose of 60 mg selinexor twice-weekly on Day 1 and 3 during each 6-week (42-day) cycle.

    Serious adverse events
    		 Phase 2 Double-blinded: selinexor Phase 2 Double-blinded: placebo Phase 2 Open-label: selinexor Phase 3 Double-blinded: placebo Phase 3 Open-label: selinexor Phase 3 Double-blinded: selinexor
    Total subjects affected by serious adverse events
         subjects affected / exposed
    4 / 27 (14.81%)
    6 / 30 (20.00%)
    13 / 24 (54.17%)
    18 / 97 (18.56%)
    25 / 63 (39.68%)
    73 / 187 (39.04%)
         number of deaths (all causes)
    18
    25
    20
    67
    43
    127
         number of deaths resulting from adverse events
    0
    1
    1
    3
    2
    4
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Cancer pain
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    0 / 97 (0.00%)
    0 / 63 (0.00%)
    1 / 187 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myelodysplastic syndrome
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    0 / 97 (0.00%)
    0 / 63 (0.00%)
    2 / 187 (1.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    Tumour pain
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    0 / 97 (0.00%)
    0 / 63 (0.00%)
    2 / 187 (1.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebral ischaemia
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    0 / 97 (0.00%)
    1 / 63 (1.59%)
    0 / 187 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Deep vein thrombosis
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    1 / 24 (4.17%)
    0 / 97 (0.00%)
    2 / 63 (3.17%)
    0 / 187 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Embolism
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    0 / 97 (0.00%)
    1 / 63 (1.59%)
    0 / 187 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Venous thrombosis
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    0 / 97 (0.00%)
    0 / 63 (0.00%)
    1 / 187 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Complication associated with device
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    0 / 97 (0.00%)
    1 / 63 (1.59%)
    0 / 187 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fatigue
         subjects affected / exposed
    0 / 27 (0.00%)
    1 / 30 (3.33%)
    0 / 24 (0.00%)
    0 / 97 (0.00%)
    1 / 63 (1.59%)
    1 / 187 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General physical health deterioration
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    0 / 97 (0.00%)
    0 / 63 (0.00%)
    2 / 187 (1.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Multiple organ dysfunction syndrome
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    1 / 97 (1.03%)
    0 / 63 (0.00%)
    0 / 187 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oedema peripheral
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    1 / 97 (1.03%)
    1 / 63 (1.59%)
    0 / 187 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pain
         subjects affected / exposed
    1 / 27 (3.70%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    0 / 97 (0.00%)
    0 / 63 (0.00%)
    1 / 187 (0.53%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    1 / 24 (4.17%)
    1 / 97 (1.03%)
    0 / 63 (0.00%)
    0 / 187 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sudden death
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    1 / 97 (1.03%)
    0 / 63 (0.00%)
    0 / 187 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory failure
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    0 / 97 (0.00%)
    0 / 63 (0.00%)
    1 / 187 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    1 / 97 (1.03%)
    1 / 63 (1.59%)
    1 / 187 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    1 / 24 (4.17%)
    1 / 97 (1.03%)
    0 / 63 (0.00%)
    1 / 187 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypoxia
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    2 / 24 (8.33%)
    0 / 97 (0.00%)
    0 / 63 (0.00%)
    0 / 187 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    0 / 97 (0.00%)
    1 / 63 (1.59%)
    3 / 187 (1.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumothorax
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    0 / 97 (0.00%)
    0 / 63 (0.00%)
    2 / 187 (1.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    1 / 97 (1.03%)
    3 / 63 (4.76%)
    2 / 187 (1.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 3
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary oedema
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    0 / 97 (0.00%)
    0 / 63 (0.00%)
    1 / 187 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    1 / 24 (4.17%)
    0 / 97 (0.00%)
    1 / 63 (1.59%)
    1 / 187 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    Psychiatric disorders
    Confusional state
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    0 / 97 (0.00%)
    1 / 63 (1.59%)
    0 / 187 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Delirium
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    1 / 24 (4.17%)
    0 / 97 (0.00%)
    0 / 63 (0.00%)
    0 / 187 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mania
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    0 / 97 (0.00%)
    0 / 63 (0.00%)
    1 / 187 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Suicide attempt
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    0 / 97 (0.00%)
    0 / 63 (0.00%)
    1 / 187 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Product issues
    Device breakage
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    0 / 97 (0.00%)
    0 / 63 (0.00%)
    1 / 187 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Ejection fraction decreased
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    0 / 97 (0.00%)
    1 / 63 (1.59%)
    0 / 187 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Transaminases increased
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    0 / 97 (0.00%)
    0 / 63 (0.00%)
    1 / 187 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Anastomotic ulcer haemorrhage
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    0 / 97 (0.00%)
    0 / 63 (0.00%)
    1 / 187 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Clavicle fracture
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    0 / 97 (0.00%)
    0 / 63 (0.00%)
    1 / 187 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Facial bones fracture
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    0 / 97 (0.00%)
    1 / 63 (1.59%)
    0 / 187 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fall
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    0 / 97 (0.00%)
    0 / 63 (0.00%)
    1 / 187 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fracture
         subjects affected / exposed
    1 / 27 (3.70%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    0 / 97 (0.00%)
    0 / 63 (0.00%)
    0 / 187 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Head injury
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    0 / 97 (0.00%)
    0 / 63 (0.00%)
    1 / 187 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hip fracture
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    0 / 97 (0.00%)
    0 / 63 (0.00%)
    1 / 187 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Limb injury
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    0 / 97 (0.00%)
    0 / 63 (0.00%)
    1 / 187 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Humerus fracture
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    0 / 97 (0.00%)
    0 / 63 (0.00%)
    1 / 187 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spinal fracture
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    0 / 97 (0.00%)
    0 / 63 (0.00%)
    1 / 187 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Wound complication
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    0 / 97 (0.00%)
    0 / 63 (0.00%)
    1 / 187 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Atrial fibrillation
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    0 / 97 (0.00%)
    0 / 63 (0.00%)
    1 / 187 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac arrest
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    1 / 24 (4.17%)
    0 / 97 (0.00%)
    0 / 63 (0.00%)
    0 / 187 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure
         subjects affected / exposed
    0 / 27 (0.00%)
    1 / 30 (3.33%)
    0 / 24 (0.00%)
    0 / 97 (0.00%)
    0 / 63 (0.00%)
    2 / 187 (1.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac ventricular thrombosis
         subjects affected / exposed
    0 / 27 (0.00%)
    1 / 30 (3.33%)
    0 / 24 (0.00%)
    0 / 97 (0.00%)
    0 / 63 (0.00%)
    0 / 187 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Cerebrovascular accident
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    0 / 97 (0.00%)
    0 / 63 (0.00%)
    1 / 187 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dizziness
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    0 / 97 (0.00%)
    0 / 63 (0.00%)
    1 / 187 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lethargy
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    0 / 97 (0.00%)
    0 / 63 (0.00%)
    1 / 187 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    0 / 97 (0.00%)
    0 / 63 (0.00%)
    2 / 187 (1.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 27 (3.70%)
    0 / 30 (0.00%)
    1 / 24 (4.17%)
    0 / 97 (0.00%)
    2 / 63 (3.17%)
    3 / 187 (1.60%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 1
    0 / 0
    2 / 2
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    0 / 97 (0.00%)
    2 / 63 (3.17%)
    2 / 187 (1.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    2 / 2
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Cataract
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    1 / 24 (4.17%)
    0 / 97 (0.00%)
    0 / 63 (0.00%)
    2 / 187 (1.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Retinal tear
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    1 / 24 (4.17%)
    0 / 97 (0.00%)
    0 / 63 (0.00%)
    0 / 187 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    1 / 97 (1.03%)
    1 / 63 (1.59%)
    7 / 187 (3.74%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    1 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    1 / 97 (1.03%)
    0 / 63 (0.00%)
    0 / 187 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    1 / 97 (1.03%)
    0 / 63 (0.00%)
    0 / 187 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dysphagia
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    0 / 97 (0.00%)
    0 / 63 (0.00%)
    1 / 187 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Enterocutaneous fistula
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    0 / 97 (0.00%)
    0 / 63 (0.00%)
    1 / 187 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastritis
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    0 / 97 (0.00%)
    0 / 63 (0.00%)
    1 / 187 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    0 / 97 (0.00%)
    0 / 63 (0.00%)
    1 / 187 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ileus
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    0 / 97 (0.00%)
    1 / 63 (1.59%)
    0 / 187 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Large intestinal obstruction
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    0 / 97 (0.00%)
    0 / 63 (0.00%)
    1 / 187 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intestinal obstruction
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    1 / 97 (1.03%)
    2 / 63 (3.17%)
    0 / 187 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intra-abdominal haemorrhage
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    0 / 97 (0.00%)
    0 / 63 (0.00%)
    1 / 187 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Large intestine perforation
         subjects affected / exposed
    0 / 27 (0.00%)
    1 / 30 (3.33%)
    1 / 24 (4.17%)
    0 / 97 (0.00%)
    0 / 63 (0.00%)
    0 / 187 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    3 / 24 (12.50%)
    0 / 97 (0.00%)
    0 / 63 (0.00%)
    4 / 187 (2.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    3 / 3
    0 / 0
    0 / 0
    4 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Obstruction gastric
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    0 / 97 (0.00%)
    0 / 63 (0.00%)
    1 / 187 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rectal haemorrhage
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    0 / 97 (0.00%)
    1 / 63 (1.59%)
    1 / 187 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rectal obstruction
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    1 / 97 (1.03%)
    0 / 63 (0.00%)
    0 / 187 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Small intestine obstruction
         subjects affected / exposed
    0 / 27 (0.00%)
    1 / 30 (3.33%)
    2 / 24 (8.33%)
    2 / 97 (2.06%)
    2 / 63 (3.17%)
    2 / 187 (1.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
    0 / 2
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Stomatitis
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    1 / 24 (4.17%)
    0 / 97 (0.00%)
    0 / 63 (0.00%)
    0 / 187 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Upper gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    0 / 97 (0.00%)
    0 / 63 (0.00%)
    2 / 187 (1.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    2 / 24 (8.33%)
    1 / 97 (1.03%)
    0 / 63 (0.00%)
    2 / 187 (1.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    2 / 2
    1 / 1
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Bile duct obstruction
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    0 / 97 (0.00%)
    1 / 63 (1.59%)
    1 / 187 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholangitis
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    0 / 97 (0.00%)
    0 / 63 (0.00%)
    1 / 187 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyperbilirubinaemia
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    0 / 97 (0.00%)
    1 / 63 (1.59%)
    1 / 187 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    0 / 27 (0.00%)
    1 / 30 (3.33%)
    0 / 24 (0.00%)
    1 / 97 (1.03%)
    2 / 63 (3.17%)
    3 / 187 (1.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    1 / 1
    0 / 2
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    Haematuria
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    0 / 97 (0.00%)
    1 / 63 (1.59%)
    1 / 187 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hydronephrosis
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    0 / 97 (0.00%)
    1 / 63 (1.59%)
    0 / 187 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal failure
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    1 / 97 (1.03%)
    0 / 63 (0.00%)
    0 / 187 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary tract obstruction
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    1 / 97 (1.03%)
    0 / 63 (0.00%)
    0 / 187 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    1 / 24 (4.17%)
    2 / 97 (2.06%)
    0 / 63 (0.00%)
    0 / 187 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Muscular weakness
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    0 / 97 (0.00%)
    0 / 63 (0.00%)
    1 / 187 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal pain
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    1 / 97 (1.03%)
    0 / 63 (0.00%)
    0 / 187 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pain in extremity
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    0 / 97 (0.00%)
    0 / 63 (0.00%)
    1 / 187 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Bacteraemia
         subjects affected / exposed
    0 / 27 (0.00%)
    1 / 30 (3.33%)
    0 / 24 (0.00%)
    0 / 97 (0.00%)
    0 / 63 (0.00%)
    0 / 187 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    0 / 97 (0.00%)
    1 / 63 (1.59%)
    0 / 187 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bronchitis viral
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    0 / 97 (0.00%)
    0 / 63 (0.00%)
    2 / 187 (1.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    1 / 97 (1.03%)
    1 / 63 (1.59%)
    1 / 187 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Device related infection
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    0 / 97 (0.00%)
    0 / 63 (0.00%)
    1 / 187 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Escherichia infection
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    0 / 97 (0.00%)
    0 / 63 (0.00%)
    1 / 187 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    0 / 97 (0.00%)
    0 / 63 (0.00%)
    2 / 187 (1.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lung abscess
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    0 / 97 (0.00%)
    0 / 63 (0.00%)
    1 / 187 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peritonitis
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    0 / 97 (0.00%)
    0 / 63 (0.00%)
    1 / 187 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Pneumonia
         subjects affected / exposed
    0 / 27 (0.00%)
    2 / 30 (6.67%)
    2 / 24 (8.33%)
    0 / 97 (0.00%)
    1 / 63 (1.59%)
    3 / 187 (1.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
    0 / 0
    0 / 1
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia klebsiella
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    1 / 97 (1.03%)
    0 / 63 (0.00%)
    0 / 187 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory syncytial virus infection
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    0 / 97 (0.00%)
    1 / 63 (1.59%)
    1 / 187 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    0 / 27 (0.00%)
    1 / 30 (3.33%)
    1 / 24 (4.17%)
    2 / 97 (2.06%)
    1 / 63 (1.59%)
    0 / 187 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    2 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    0 / 97 (0.00%)
    0 / 63 (0.00%)
    1 / 187 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    1 / 97 (1.03%)
    0 / 63 (0.00%)
    0 / 187 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    1 / 97 (1.03%)
    1 / 63 (1.59%)
    1 / 187 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    1 / 97 (1.03%)
    1 / 63 (1.59%)
    2 / 187 (1.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    1 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dehydration
         subjects affected / exposed
    1 / 27 (3.70%)
    0 / 30 (0.00%)
    1 / 24 (4.17%)
    0 / 97 (0.00%)
    0 / 63 (0.00%)
    2 / 187 (1.07%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyperglycaemia
         subjects affected / exposed
    1 / 27 (3.70%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    0 / 97 (0.00%)
    0 / 63 (0.00%)
    2 / 187 (1.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypocalcaemia
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    0 / 97 (0.00%)
    1 / 63 (1.59%)
    0 / 187 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    0 / 97 (0.00%)
    1 / 63 (1.59%)
    2 / 187 (1.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Malnutrition
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    0 / 97 (0.00%)
    0 / 63 (0.00%)
    1 / 187 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Phase 2 Double-blinded: selinexor Phase 2 Double-blinded: placebo Phase 2 Open-label: selinexor Phase 3 Double-blinded: placebo Phase 3 Open-label: selinexor Phase 3 Double-blinded: selinexor
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    27 / 27 (100.00%)
    29 / 30 (96.67%)
    24 / 24 (100.00%)
    94 / 97 (96.91%)
    62 / 63 (98.41%)
    186 / 187 (99.47%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Tumour pain
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    4 / 97 (4.12%)
    4 / 63 (6.35%)
    4 / 187 (2.14%)
         occurrences all number
    0
    0
    0
    4
    4
    4
    Vascular disorders
    Hot flush
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    1 / 24 (4.17%)
    3 / 97 (3.09%)
    4 / 63 (6.35%)
    3 / 187 (1.60%)
         occurrences all number
    0
    0
    1
    3
    4
    3
    Hypertension
         subjects affected / exposed
    5 / 27 (18.52%)
    3 / 30 (10.00%)
    3 / 24 (12.50%)
    10 / 97 (10.31%)
    6 / 63 (9.52%)
    22 / 187 (11.76%)
         occurrences all number
    5
    3
    3
    10
    6
    22
    Hypotension
         subjects affected / exposed
    4 / 27 (14.81%)
    3 / 30 (10.00%)
    3 / 24 (12.50%)
    3 / 97 (3.09%)
    5 / 63 (7.94%)
    23 / 187 (12.30%)
         occurrences all number
    4
    3
    3
    3
    5
    23
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    1 / 27 (3.70%)
    0 / 30 (0.00%)
    1 / 24 (4.17%)
    10 / 97 (10.31%)
    13 / 63 (20.63%)
    58 / 187 (31.02%)
         occurrences all number
    1
    0
    1
    10
    13
    58
    Chills
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    2 / 24 (8.33%)
    7 / 97 (7.22%)
    1 / 63 (1.59%)
    11 / 187 (5.88%)
         occurrences all number
    0
    0
    2
    7
    1
    11
    Fatigue
         subjects affected / exposed
    15 / 27 (55.56%)
    14 / 30 (46.67%)
    18 / 24 (75.00%)
    31 / 97 (31.96%)
    33 / 63 (52.38%)
    96 / 187 (51.34%)
         occurrences all number
    15
    14
    18
    31
    33
    96
    General physical health deterioration
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    2 / 97 (2.06%)
    4 / 63 (6.35%)
    2 / 187 (1.07%)
         occurrences all number
    0
    0
    0
    2
    4
    2
    Influenza like illness
         subjects affected / exposed
    1 / 27 (3.70%)
    3 / 30 (10.00%)
    1 / 24 (4.17%)
    1 / 97 (1.03%)
    0 / 63 (0.00%)
    3 / 187 (1.60%)
         occurrences all number
    1
    3
    1
    1
    0
    3
    Malaise
         subjects affected / exposed
    3 / 27 (11.11%)
    1 / 30 (3.33%)
    3 / 24 (12.50%)
    2 / 97 (2.06%)
    1 / 63 (1.59%)
    2 / 187 (1.07%)
         occurrences all number
    3
    1
    3
    2
    1
    2
    Non-cardiac chest pain
         subjects affected / exposed
    0 / 27 (0.00%)
    2 / 30 (6.67%)
    1 / 24 (4.17%)
    2 / 97 (2.06%)
    2 / 63 (3.17%)
    5 / 187 (2.67%)
         occurrences all number
    0
    2
    1
    2
    2
    5
    Oedema peripheral
         subjects affected / exposed
    3 / 27 (11.11%)
    3 / 30 (10.00%)
    3 / 24 (12.50%)
    12 / 97 (12.37%)
    10 / 63 (15.87%)
    30 / 187 (16.04%)
         occurrences all number
    3
    3
    3
    12
    10
    30
    Pain
         subjects affected / exposed
    1 / 27 (3.70%)
    2 / 30 (6.67%)
    1 / 24 (4.17%)
    0 / 97 (0.00%)
    0 / 63 (0.00%)
    4 / 187 (2.14%)
         occurrences all number
    1
    2
    1
    0
    0
    4
    Pyrexia
         subjects affected / exposed
    1 / 27 (3.70%)
    4 / 30 (13.33%)
    1 / 24 (4.17%)
    9 / 97 (9.28%)
    8 / 63 (12.70%)
    20 / 187 (10.70%)
         occurrences all number
    1
    4
    1
    9
    8
    20
    Respiratory, thoracic and mediastinal disorders
    Aspiration
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    2 / 24 (8.33%)
    0 / 97 (0.00%)
    0 / 63 (0.00%)
    0 / 187 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    0
    Cough
         subjects affected / exposed
    4 / 27 (14.81%)
    3 / 30 (10.00%)
    7 / 24 (29.17%)
    7 / 97 (7.22%)
    7 / 63 (11.11%)
    30 / 187 (16.04%)
         occurrences all number
    4
    3
    7
    7
    7
    30
    Dyspnoea
         subjects affected / exposed
    0 / 27 (0.00%)
    3 / 30 (10.00%)
    7 / 24 (29.17%)
    11 / 97 (11.34%)
    10 / 63 (15.87%)
    34 / 187 (18.18%)
         occurrences all number
    0
    3
    7
    11
    10
    34
    Epistaxis
         subjects affected / exposed
    3 / 27 (11.11%)
    1 / 30 (3.33%)
    0 / 24 (0.00%)
    0 / 97 (0.00%)
    1 / 63 (1.59%)
    6 / 187 (3.21%)
         occurrences all number
    3
    1
    0
    0
    1
    6
    Nasal congestion
         subjects affected / exposed
    3 / 27 (11.11%)
    1 / 30 (3.33%)
    1 / 24 (4.17%)
    0 / 97 (0.00%)
    4 / 63 (6.35%)
    7 / 187 (3.74%)
         occurrences all number
    3
    1
    1
    0
    4
    7
    Oropharyngeal pain
         subjects affected / exposed
    1 / 27 (3.70%)
    2 / 30 (6.67%)
    0 / 24 (0.00%)
    1 / 97 (1.03%)
    1 / 63 (1.59%)
    7 / 187 (3.74%)
         occurrences all number
    1
    2
    0
    1
    1
    7
    Pleural effusion
         subjects affected / exposed
    0 / 27 (0.00%)
    2 / 30 (6.67%)
    0 / 24 (0.00%)
    0 / 97 (0.00%)
    3 / 63 (4.76%)
    2 / 187 (1.07%)
         occurrences all number
    0
    2
    0
    0
    3
    2
    Pulmonary embolism
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    2 / 24 (8.33%)
    0 / 97 (0.00%)
    0 / 63 (0.00%)
    5 / 187 (2.67%)
         occurrences all number
    0
    0
    2
    0
    0
    5
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    0 / 27 (0.00%)
    2 / 30 (6.67%)
    1 / 24 (4.17%)
    0 / 97 (0.00%)
    4 / 63 (6.35%)
    6 / 187 (3.21%)
         occurrences all number
    0
    2
    1
    0
    4
    6
    Confusional state
         subjects affected / exposed
    1 / 27 (3.70%)
    0 / 30 (0.00%)
    2 / 24 (8.33%)
    1 / 97 (1.03%)
    1 / 63 (1.59%)
    6 / 187 (3.21%)
         occurrences all number
    1
    0
    2
    1
    1
    6
    Depression
         subjects affected / exposed
    0 / 27 (0.00%)
    1 / 30 (3.33%)
    2 / 24 (8.33%)
    2 / 97 (2.06%)
    5 / 63 (7.94%)
    11 / 187 (5.88%)
         occurrences all number
    0
    1
    2
    2
    5
    11
    Insomnia
         subjects affected / exposed
    2 / 27 (7.41%)
    1 / 30 (3.33%)
    2 / 24 (8.33%)
    4 / 97 (4.12%)
    2 / 63 (3.17%)
    21 / 187 (11.23%)
         occurrences all number
    2
    1
    2
    4
    2
    21
    Investigations
    Activated partial thromboplastin time prolonged
         subjects affected / exposed
    0 / 27 (0.00%)
    4 / 30 (13.33%)
    2 / 24 (8.33%)
    3 / 97 (3.09%)
    4 / 63 (6.35%)
    4 / 187 (2.14%)
         occurrences all number
    0
    4
    2
    3
    4
    4
    Alanine aminotransferase increased
         subjects affected / exposed
    6 / 27 (22.22%)
    2 / 30 (6.67%)
    3 / 24 (12.50%)
    5 / 97 (5.15%)
    6 / 63 (9.52%)
    16 / 187 (8.56%)
         occurrences all number
    6
    2
    3
    5
    6
    16
    Aspartate aminotransferase increased
         subjects affected / exposed
    3 / 27 (11.11%)
    2 / 30 (6.67%)
    2 / 24 (8.33%)
    5 / 97 (5.15%)
    7 / 63 (11.11%)
    11 / 187 (5.88%)
         occurrences all number
    3
    2
    2
    5
    7
    11
    Blood alkaline phosphatase increased
         subjects affected / exposed
    6 / 27 (22.22%)
    7 / 30 (23.33%)
    3 / 24 (12.50%)
    10 / 97 (10.31%)
    5 / 63 (7.94%)
    14 / 187 (7.49%)
         occurrences all number
    6
    7
    3
    10
    5
    14
    Blood lactate dehydrogenase increased
         subjects affected / exposed
    1 / 27 (3.70%)
    1 / 30 (3.33%)
    3 / 24 (12.50%)
    1 / 97 (1.03%)
    1 / 63 (1.59%)
    0 / 187 (0.00%)
         occurrences all number
    1
    1
    3
    1
    1
    0
    Electrocardiogram QT prolonged
         subjects affected / exposed
    2 / 27 (7.41%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    0 / 97 (0.00%)
    0 / 63 (0.00%)
    5 / 187 (2.67%)
         occurrences all number
    2
    0
    0
    0
    0
    5
    International normalised ratio increased
         subjects affected / exposed
    0 / 27 (0.00%)
    2 / 30 (6.67%)
    0 / 24 (0.00%)
    2 / 97 (2.06%)
    3 / 63 (4.76%)
    5 / 187 (2.67%)
         occurrences all number
    0
    2
    0
    2
    3
    5
    Weight decreased
         subjects affected / exposed
    14 / 27 (51.85%)
    0 / 30 (0.00%)
    15 / 24 (62.50%)
    9 / 97 (9.28%)
    25 / 63 (39.68%)
    81 / 187 (43.32%)
         occurrences all number
    14
    0
    15
    9
    25
    81
    Blood creatine phosphokinase increased
         subjects affected / exposed
    3 / 27 (11.11%)
    1 / 30 (3.33%)
    0 / 24 (0.00%)
    3 / 97 (3.09%)
    4 / 63 (6.35%)
    5 / 187 (2.67%)
         occurrences all number
    3
    1
    0
    3
    4
    5
    Cardiac disorders
    Sinus Tachycardia
         subjects affected / exposed
    0 / 27 (0.00%)
    1 / 30 (3.33%)
    1 / 24 (4.17%)
    6 / 97 (6.19%)
    6 / 63 (9.52%)
    7 / 187 (3.74%)
         occurrences all number
    0
    1
    1
    6
    6
    7
    Tachycardia
         subjects affected / exposed
    2 / 27 (7.41%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    3 / 97 (3.09%)
    4 / 63 (6.35%)
    3 / 187 (1.60%)
         occurrences all number
    2
    0
    0
    3
    4
    3
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    7 / 27 (25.93%)
    3 / 30 (10.00%)
    4 / 24 (16.67%)
    6 / 97 (6.19%)
    11 / 63 (17.46%)
    45 / 187 (24.06%)
         occurrences all number
    7
    3
    4
    6
    11
    45
    Dysgeusia
         subjects affected / exposed
    10 / 27 (37.04%)
    2 / 30 (6.67%)
    6 / 24 (25.00%)
    4 / 97 (4.12%)
    12 / 63 (19.05%)
    51 / 187 (27.27%)
         occurrences all number
    10
    2
    6
    4
    12
    51
    Headache
         subjects affected / exposed
    4 / 27 (14.81%)
    3 / 30 (10.00%)
    3 / 24 (12.50%)
    3 / 97 (3.09%)
    7 / 63 (11.11%)
    23 / 187 (12.30%)
         occurrences all number
    4
    3
    3
    3
    7
    23
    Sciatica
         subjects affected / exposed
    2 / 27 (7.41%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    3 / 97 (3.09%)
    1 / 63 (1.59%)
    1 / 187 (0.53%)
         occurrences all number
    2
    0
    0
    3
    1
    1
    Syncope
         subjects affected / exposed
    1 / 27 (3.70%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    0 / 97 (0.00%)
    3 / 63 (4.76%)
    11 / 187 (5.88%)
         occurrences all number
    1
    0
    0
    0
    3
    11
    Taste disorder
         subjects affected / exposed
    3 / 27 (11.11%)
    0 / 30 (0.00%)
    2 / 24 (8.33%)
    1 / 97 (1.03%)
    5 / 63 (7.94%)
    8 / 187 (4.28%)
         occurrences all number
    3
    0
    2
    1
    5
    8
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    16 / 27 (59.26%)
    9 / 30 (30.00%)
    10 / 24 (41.67%)
    22 / 97 (22.68%)
    26 / 63 (41.27%)
    91 / 187 (48.66%)
         occurrences all number
    16
    9
    10
    22
    26
    91
    Leukopenia
         subjects affected / exposed
    9 / 27 (33.33%)
    1 / 30 (3.33%)
    5 / 24 (20.83%)
    1 / 97 (1.03%)
    13 / 63 (20.63%)
    26 / 187 (13.90%)
         occurrences all number
    9
    1
    5
    1
    13
    26
    Lymphopenia
         subjects affected / exposed
    0 / 27 (0.00%)
    1 / 30 (3.33%)
    1 / 24 (4.17%)
    4 / 97 (4.12%)
    6 / 63 (9.52%)
    14 / 187 (7.49%)
         occurrences all number
    0
    1
    1
    4
    6
    14
    Neutropenia
         subjects affected / exposed
    8 / 27 (29.63%)
    1 / 30 (3.33%)
    6 / 24 (25.00%)
    1 / 97 (1.03%)
    12 / 63 (19.05%)
    38 / 187 (20.32%)
         occurrences all number
    8
    1
    6
    1
    12
    38
    Thrombocytopenia
         subjects affected / exposed
    11 / 27 (40.74%)
    2 / 30 (6.67%)
    11 / 24 (45.83%)
    5 / 97 (5.15%)
    24 / 63 (38.10%)
    72 / 187 (38.50%)
         occurrences all number
    11
    2
    11
    5
    24
    72
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    2 / 24 (8.33%)
    2 / 97 (2.06%)
    0 / 63 (0.00%)
    4 / 187 (2.14%)
         occurrences all number
    0
    0
    2
    2
    0
    4
    Eye disorders
    Cataract
         subjects affected / exposed
    2 / 27 (7.41%)
    1 / 30 (3.33%)
    1 / 24 (4.17%)
    1 / 97 (1.03%)
    2 / 63 (3.17%)
    7 / 187 (3.74%)
         occurrences all number
    2
    1
    1
    1
    2
    7
    Photopsia
         subjects affected / exposed
    2 / 27 (7.41%)
    0 / 30 (0.00%)
    1 / 24 (4.17%)
    0 / 97 (0.00%)
    1 / 63 (1.59%)
    9 / 187 (4.81%)
         occurrences all number
    2
    0
    1
    0
    1
    9
    Visual Impairement
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    0 / 97 (0.00%)
    1 / 63 (1.59%)
    10 / 187 (5.35%)
         occurrences all number
    0
    0
    0
    0
    1
    10
    Vision Blurred
         subjects affected / exposed
    8 / 27 (29.63%)
    2 / 30 (6.67%)
    9 / 24 (37.50%)
    3 / 97 (3.09%)
    8 / 63 (12.70%)
    42 / 187 (22.46%)
         occurrences all number
    8
    2
    9
    3
    8
    42
    Vitreous floaters
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    3 / 24 (12.50%)
    1 / 97 (1.03%)
    1 / 63 (1.59%)
    0 / 187 (0.00%)
         occurrences all number
    0
    0
    3
    1
    1
    0
    Gastrointestinal disorders
    Abdominal distension
         subjects affected / exposed
    2 / 27 (7.41%)
    1 / 30 (3.33%)
    2 / 24 (8.33%)
    6 / 97 (6.19%)
    1 / 63 (1.59%)
    11 / 187 (5.88%)
         occurrences all number
    2
    1
    2
    6
    1
    11
    Abdominal pain
         subjects affected / exposed
    6 / 27 (22.22%)
    8 / 30 (26.67%)
    5 / 24 (20.83%)
    30 / 97 (30.93%)
    13 / 63 (20.63%)
    49 / 187 (26.20%)
         occurrences all number
    6
    8
    5
    30
    13
    49
    Constipation
         subjects affected / exposed
    6 / 27 (22.22%)
    8 / 30 (26.67%)
    6 / 24 (25.00%)
    23 / 97 (23.71%)
    14 / 63 (22.22%)
    74 / 187 (39.57%)
         occurrences all number
    6
    8
    6
    23
    14
    74
    Diarrhoea
         subjects affected / exposed
    8 / 27 (29.63%)
    5 / 30 (16.67%)
    7 / 24 (29.17%)
    17 / 97 (17.53%)
    18 / 63 (28.57%)
    75 / 187 (40.11%)
         occurrences all number
    8
    5
    7
    17
    18
    75
    Dry mouth
         subjects affected / exposed
    1 / 27 (3.70%)
    0 / 30 (0.00%)
    2 / 24 (8.33%)
    1 / 97 (1.03%)
    3 / 63 (4.76%)
    11 / 187 (5.88%)
         occurrences all number
    1
    0
    2
    1
    3
    11
    Dyspepsia
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    1 / 24 (4.17%)
    6 / 97 (6.19%)
    4 / 63 (6.35%)
    18 / 187 (9.63%)
         occurrences all number
    0
    0
    1
    6
    4
    18
    Flatulence
         subjects affected / exposed
    1 / 27 (3.70%)
    1 / 30 (3.33%)
    0 / 24 (0.00%)
    1 / 97 (1.03%)
    1 / 63 (1.59%)
    10 / 187 (5.35%)
         occurrences all number
    1
    1
    0
    1
    1
    10
    Nausea
         subjects affected / exposed
    24 / 27 (88.89%)
    10 / 30 (33.33%)
    20 / 24 (83.33%)
    38 / 97 (39.18%)
    45 / 63 (71.43%)
    151 / 187 (80.75%)
         occurrences all number
    24
    10
    20
    38
    45
    151
    Gastroesophageal reflux disease
         subjects affected / exposed
    1 / 27 (3.70%)
    1 / 30 (3.33%)
    1 / 24 (4.17%)
    1 / 97 (1.03%)
    0 / 63 (0.00%)
    11 / 187 (5.88%)
         occurrences all number
    1
    1
    1
    1
    0
    11
    Vomiting
         subjects affected / exposed
    15 / 27 (55.56%)
    4 / 30 (13.33%)
    14 / 24 (58.33%)
    12 / 97 (12.37%)
    31 / 63 (49.21%)
    93 / 187 (49.73%)
         occurrences all number
    15
    4
    14
    12
    31
    93
    Hepatobiliary disorders
    Hyperbilirubinaemia
         subjects affected / exposed
    1 / 27 (3.70%)
    2 / 30 (6.67%)
    0 / 24 (0.00%)
    2 / 97 (2.06%)
    4 / 63 (6.35%)
    3 / 187 (1.60%)
         occurrences all number
    1
    2
    0
    2
    4
    3
    Skin and subcutaneous tissue disorders
    Night sweats
         subjects affected / exposed
    3 / 27 (11.11%)
    0 / 30 (0.00%)
    2 / 24 (8.33%)
    0 / 97 (0.00%)
    0 / 63 (0.00%)
    13 / 187 (6.95%)
         occurrences all number
    3
    0
    2
    0
    0
    13
    Rash
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    2 / 24 (8.33%)
    5 / 97 (5.15%)
    0 / 63 (0.00%)
    5 / 187 (2.67%)
         occurrences all number
    0
    0
    2
    5
    0
    5
    Renal and urinary disorders
    Haematuria
         subjects affected / exposed
    3 / 27 (11.11%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    7 / 97 (7.22%)
    0 / 63 (0.00%)
    7 / 187 (3.74%)
         occurrences all number
    3
    0
    0
    7
    0
    7
    Micturition urgency
         subjects affected / exposed
    2 / 27 (7.41%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    1 / 97 (1.03%)
    0 / 63 (0.00%)
    1 / 187 (0.53%)
         occurrences all number
    2
    0
    0
    1
    0
    1
    Pollakiuria
         subjects affected / exposed
    2 / 27 (7.41%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    3 / 97 (3.09%)
    0 / 63 (0.00%)
    6 / 187 (3.21%)
         occurrences all number
    2
    0
    0
    3
    0
    6
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    3 / 27 (11.11%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    5 / 97 (5.15%)
    3 / 63 (4.76%)
    9 / 187 (4.81%)
         occurrences all number
    3
    0
    0
    5
    3
    9
    Back pain
         subjects affected / exposed
    4 / 27 (14.81%)
    3 / 30 (10.00%)
    4 / 24 (16.67%)
    12 / 97 (12.37%)
    7 / 63 (11.11%)
    26 / 187 (13.90%)
         occurrences all number
    4
    3
    4
    12
    7
    26
    Muscle spasms
         subjects affected / exposed
    1 / 27 (3.70%)
    0 / 30 (0.00%)
    1 / 24 (4.17%)
    3 / 97 (3.09%)
    1 / 63 (1.59%)
    12 / 187 (6.42%)
         occurrences all number
    1
    0
    1
    3
    1
    12
    Muscular weakness
         subjects affected / exposed
    2 / 27 (7.41%)
    0 / 30 (0.00%)
    3 / 24 (12.50%)
    2 / 97 (2.06%)
    5 / 63 (7.94%)
    11 / 187 (5.88%)
         occurrences all number
    2
    0
    3
    2
    5
    11
    Myalgia
         subjects affected / exposed
    0 / 27 (0.00%)
    1 / 30 (3.33%)
    1 / 24 (4.17%)
    7 / 97 (7.22%)
    1 / 63 (1.59%)
    9 / 187 (4.81%)
         occurrences all number
    0
    1
    1
    7
    1
    9
    Pain in extremity
         subjects affected / exposed
    1 / 27 (3.70%)
    1 / 30 (3.33%)
    1 / 24 (4.17%)
    4 / 97 (4.12%)
    5 / 63 (7.94%)
    11 / 187 (5.88%)
         occurrences all number
    1
    1
    1
    4
    5
    11
    Infections and infestations
    Rhinitis
         subjects affected / exposed
    2 / 27 (7.41%)
    0 / 30 (0.00%)
    1 / 24 (4.17%)
    0 / 97 (0.00%)
    0 / 63 (0.00%)
    1 / 187 (0.53%)
         occurrences all number
    2
    0
    1
    0
    0
    1
    Sinusitis
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    2 / 24 (8.33%)
    2 / 97 (2.06%)
    2 / 63 (3.17%)
    2 / 187 (1.07%)
         occurrences all number
    0
    0
    2
    2
    2
    2
    Urinary tract infection
         subjects affected / exposed
    5 / 27 (18.52%)
    3 / 30 (10.00%)
    3 / 24 (12.50%)
    8 / 97 (8.25%)
    4 / 63 (6.35%)
    13 / 187 (6.95%)
         occurrences all number
    5
    3
    3
    8
    4
    13
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    15 / 27 (55.56%)
    5 / 30 (16.67%)
    14 / 24 (58.33%)
    21 / 97 (21.65%)
    32 / 63 (50.79%)
    114 / 187 (60.96%)
         occurrences all number
    15
    5
    14
    21
    32
    114
    Dehydration
         subjects affected / exposed
    1 / 27 (3.70%)
    1 / 30 (3.33%)
    3 / 24 (12.50%)
    3 / 97 (3.09%)
    3 / 63 (4.76%)
    11 / 187 (5.88%)
         occurrences all number
    1
    1
    3
    3
    3
    11
    Hypercreatininaemia
         subjects affected / exposed
    4 / 27 (14.81%)
    5 / 30 (16.67%)
    7 / 24 (29.17%)
    13 / 97 (13.40%)
    9 / 63 (14.29%)
    42 / 187 (22.46%)
         occurrences all number
    4
    5
    7
    13
    9
    42
    Hyperglycaemia
         subjects affected / exposed
    9 / 27 (33.33%)
    3 / 30 (10.00%)
    2 / 24 (8.33%)
    8 / 97 (8.25%)
    7 / 63 (11.11%)
    21 / 187 (11.23%)
         occurrences all number
    9
    3
    2
    8
    7
    21
    Hyperkalaemia
         subjects affected / exposed
    0 / 27 (0.00%)
    2 / 30 (6.67%)
    4 / 24 (16.67%)
    2 / 97 (2.06%)
    5 / 63 (7.94%)
    13 / 187 (6.95%)
         occurrences all number
    0
    2
    4
    2
    5
    13
    Hyperuricaemia
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 30 (0.00%)
    0 / 24 (0.00%)
    2 / 97 (2.06%)
    4 / 63 (6.35%)
    5 / 187 (2.67%)
         occurrences all number
    0
    0
    0
    2
    4
    5
    Hypoalbuminaemia
         subjects affected / exposed
    4 / 27 (14.81%)
    5 / 30 (16.67%)
    1 / 24 (4.17%)
    8 / 97 (8.25%)
    5 / 63 (7.94%)
    10 / 187 (5.35%)
         occurrences all number
    4
    5
    1
    8
    5
    10
    Hypocalcaemia
         subjects affected / exposed
    4 / 27 (14.81%)
    0 / 30 (0.00%)
    1 / 24 (4.17%)
    4 / 97 (4.12%)
    4 / 63 (6.35%)
    8 / 187 (4.28%)
         occurrences all number
    4
    0
    1
    4
    4
    8
    Hypokalaemia
         subjects affected / exposed
    2 / 27 (7.41%)
    4 / 30 (13.33%)
    1 / 24 (4.17%)
    5 / 97 (5.15%)
    1 / 63 (1.59%)
    20 / 187 (10.70%)
         occurrences all number
    2
    4
    1
    5
    1
    20
    Hypochloraemia
         subjects affected / exposed
    3 / 27 (11.11%)
    0 / 30 (0.00%)
    3 / 24 (12.50%)
    2 / 97 (2.06%)
    2 / 63 (3.17%)
    6 / 187 (3.21%)
         occurrences all number
    3
    0
    3
    2
    2
    6
    Hypomagnesaemia
         subjects affected / exposed
    3 / 27 (11.11%)
    3 / 30 (10.00%)
    3 / 24 (12.50%)
    2 / 97 (2.06%)
    1 / 63 (1.59%)
    24 / 187 (12.83%)
         occurrences all number
    3
    3
    3
    2
    1
    24
    Hyponatraemia
         subjects affected / exposed
    9 / 27 (33.33%)
    6 / 30 (20.00%)
    10 / 24 (41.67%)
    8 / 97 (8.25%)
    11 / 63 (17.46%)
    52 / 187 (27.81%)
         occurrences all number
    9
    6
    10
    8
    11
    52
    Hypophosphataemia
         subjects affected / exposed
    3 / 27 (11.11%)
    1 / 30 (3.33%)
    1 / 24 (4.17%)
    3 / 97 (3.09%)
    7 / 63 (11.11%)
    13 / 187 (6.95%)
         occurrences all number
    3
    1
    1
    3
    7
    13

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    11 Mar 2016
    Protocol Amendment 1: Inclusion criterion #7 was changed due to radiologic evidence of disease progression within 6 months prior to randomization. If the subject received other intervening therapy after documented disease progression, further disease progression was be documented after the completion of the intervening therapy. This change was consistent with information provided to clinical sites in a memorandum dated 28 Jan 2016. To remove the requirement for a second biopsy collected from adolescent/pediatric subjects for exploratory studies if there appears to be a potential for serious risk for the subject.
    01 Nov 2016
    Protocol Amendment 2: Added PFS according to the Investigator based on clinical and/or radiologic criteria as a secondary objective for Phase 3 and revised the order of the secondary efficacy objectives and endpoints for Phase 2 (revised efficacy endpoint order: TTP, ORR, DOR, tumor glucose metabolism) and Phase 3 (revised efficacy endpoint order: OS, TTP, QoL, ORR, DOR, PFS according to the Investigator). Randomization of subject was updated to stratify based on the number of prior systemic therapies (1 vs ≥ 2) and prior eribulin use (prior eribulin vs no prior eribulin) as requested by EMA SAWP. Clarified the purpose of the analysis of PFS at the end of Phase 2. The analysis of PFS at the end of Phase 2 was used as a guideline on whether or not to continue enrolling patients in Phase 3.
    06 Jul 2017
    Protocol Amendment 3: Added an exception to the requirement that subjects would either continue study drug until PD was confirmed by the IRC or discontinue study drug, complete the EoT Visit, and be followed for survival.
    29 Sep 2017
    Protocol Amendment 4: The evaluation of response and progression of disease was changed from WHO to RECIST v1.1 as agreed to with the FDA. Updated the inclusion criteria to clarify the documentation for DDLS that was required for eligibility, added an exception to the radiologic evidence of PD requirement for subjects who discontinued their most recent treatment after no more than 1 dose, and changed the renal function threshold. Added pregnancy testing (serum hCG or high sensitivity urine) for premenopausal females of childbearing potential prior to dosing on Day 1 of Cycles ≥ 2 while on treatment. Updated the supportive care guidance (including TLS) and standard safety language. Aligned the definition of progression-free survival (PFS) for the primary objectives and broadened secondary and exploratory endpoint definitions.
    23 Aug 2018
    Protocol Amendment 5: Moved the exclusion for subjects who have a circulating lymphocyte count of >50,000/µL from an inclusion criterion to an exclusion criterion and specified that it applied only to subjects in France.
    10 Sep 2018
    Protocol Amendment 6: Updated the language based on results from Study KCP-330-003 that demonstrated that food does not affect the PK parameters of selinexor. Acute cerebellar syndrome is no longer considered to be an important potential risk for selinexor. Corrected the definition of PFS. Revised SAE reporting to the DSMB. Removed censoring rule for OS for non-inferiority. Revised PFS according to the Investigator. Revised exclusion criterion #6 regarding hepatitis.
    30 Jan 2020
    Protocol Amendment 7: Increased the number of enrolled subjects in the Phase 3 portion of the study to approximately 277 subjects sample size recalculated due to increased accrual period.
    21 May 2020
    Protocol Amendment 8: Efficacy and QoL endpoints were modified. Added outcome of interim analysis. Exploratory endpoints PFS, ORR, and DOR, tumor response at 6 weeks FDG-PET (Phase 2 only) and CT (diagnostic), and PFS2 were removed.

    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
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