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    Clinical Trial Results:
    A Phase 1b/2 Study of TAK-981 Plus Pembrolizumab to Evaluate the Safety, Tolerability, and Antitumor Activity of the Combination in Patients With Select Advanced or Metastatic Solid Tumors

    Summary
    EudraCT number
    		 2020-004325-23
    Trial protocol
    		 LT   LV   HR  
    Global end of trial date
    29 Oct 2024

    Results information
    Results version number
    		 v1(current)
    This version publication date
    13 Nov 2025
    First version publication date
    13 Nov 2025
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    TAK-981-1502
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT04381650
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Takeda
    Sponsor organisation address
    95 Hayden Ave, Lexington, MA, United States, 02421
    Public contact
    Study Director, Takeda, TrialDisclosures@takeda.com
    Scientific contact
    Study Director, Takeda, TrialDisclosures@takeda.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
    29 Oct 2024
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    29 Oct 2024
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The main aim of the study is to evaluate the safety, tolerability, and preliminary efficacy of TAK-981 in combination with pembrolizumab in pariticipants who have select advanced or metastatic solid tumors.
    Protection of trial subjects
    Participant signed an informed consent form (ICF) before participating in the study.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    17 Aug 2020
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Brazil: 35
    Country: Number of subjects enrolled
    Japan: 18
    Country: Number of subjects enrolled
    China: 13
    Country: Number of subjects enrolled
    Croatia: 5
    Country: Number of subjects enrolled
    Latvia: 3
    Country: Number of subjects enrolled
    Lithuania: 5
    Country: Number of subjects enrolled
    Poland: 18
    Country: Number of subjects enrolled
    Switzerland: 6
    Country: Number of subjects enrolled
    United States: 58
    Worldwide total number of subjects
    161
    EEA total number of subjects
    31
    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)
    103
    From 65 to 84 years
    57
    85 years and over
    1

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Participants took part in the study at various investigative sites throughout the world from 17 August 2020 to 29 October 2024.

    Pre-assignment
    Screening details
    		 Participants with a diagnosis of advanced or metastatic solid tumors were enrolled in this study consisting of Phase 1b (Dose Escalation cohorts), and Phase 2 (Dose Expansion cohorts) periods to receive TAK-981 and pembrolizumab.

    Period 1
    Period 1 title
    Phase 1b (Dose Escalation)
    Is this the baseline period?
    		 Yes
    Allocation method
    Non-randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Dose Escalation: TAK-981 40 mg + Pembrolizumab
    Arm description
    		 Participants received TAK-981 40 mg, IV infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle and pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle until the RP2D was determined (for a maximum of 24 months).
    Arm type
    		 Experimental

    Investigational medicinal product name
    Pembrolizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months.

    Investigational medicinal product name
    TAK-981
    Investigational medicinal product code
    Other name
    Subasumstat
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    TAK-981 40 mg, IV infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle.

    Arm title
    		 Dose Escalation: TAK-981 60 mg + Pembrolizumab
    Arm description
    		 Participants received TAK-981 60 mg, IV infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle and pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle until the RP2D was determined (for a maximum of 24 months).
    Arm type
    		 Experimental

    Investigational medicinal product name
    TAK-981
    Investigational medicinal product code
    Other name
    Subasumstat
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    TAK-981 60 mg, IV infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle.

    Investigational medicinal product name
    Pembrolizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months.

    Arm title
    		 Dose Escalation: TAK-981 90 mg + Pembrolizumab
    Arm description
    		 Participants received TAK-981 90 mg, IV infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle and pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle until the RP2D was determined (for a maximum of 24 months).
    Arm type
    		 Experimental

    Investigational medicinal product name
    TAK-981
    Investigational medicinal product code
    Other name
    Subasumstat
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    TAK-981 90 mg, IV infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle.

    Investigational medicinal product name
    Pembrolizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months.

    Arm title
    		 Dose Escalation: TAK-981 120 mg + Pembrolizumab
    Arm description
    		 Participants received TAK-981, 120 mg, IV infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle and pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle until the RP2D was determined (for a maximum of 24 months).
    Arm type
    		 Experimental

    Investigational medicinal product name
    TAK-981
    Investigational medicinal product code
    Other name
    Subasumstat
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    TAK-981 120 mg, IV infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle.

    Investigational medicinal product name
    Pembrolizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months.

    Number of subjects in period 1 [1]
    		Dose Escalation: TAK-981 40 mg + Pembrolizumab Dose Escalation: TAK-981 60 mg + Pembrolizumab Dose Escalation: TAK-981 90 mg + Pembrolizumab Dose Escalation: TAK-981 120 mg + Pembrolizumab
    Started
    3
    6
    33
    19
    Completed
    2
    2
    9
    4
    Not completed
    1
    4
    24
    15
         Consent withdrawn by subject
    -
    -
    11
    4
         Reason Not Specified
    -
    1
    1
    1
         Progressive Disease
    1
    3
    12
    8
         New anti-cancer therapy
    -
    -
    -
    1
         Lost to follow-up
    -
    -
    -
    1
    Notes
    [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial because this is a two-phase study wherein participants were newly recruited in each phase.
    Period 2
    Period 2 title
    Phase 2 (Dose Expansion)
    Is this the baseline period?
    		 No
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded
    Blinding implementation details
    The arms in Period 2: Dose Expansion are mutually exclusive. However, due to database limitation which does not allow a greater number of participants to be present in the subsequent period [as compared to the preceding period], an alternative selection has been made.

    Arms
    Are arms mutually exclusive
    No

    Arm title
    		 Dose Expansion: Cohort A: Non-squamous NSCLC TAK-981 90 mg
    Arm description
    		 Participants with non-squamous NSCLC received TAK-981 as IV infusion on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle up to disease progression or 24-months and pembrolizumab 200 mg IV infusion as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Pembrolizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months.

    Investigational medicinal product name
    TAK-981
    Investigational medicinal product code
    Other name
    Subasumstat
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    TAK-981 40 mg, IV infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle.

    Arm title
    		 Dose Expansion: Cohort A: Non-squamous NSCLC TAK-981 120 mg
    Arm description
    		 Participants with non-squamous NSCLC received TAK-981 as IV infusion on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle up to disease progression or 24-months and pembrolizumab 200 mg IV infusion as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months.
    Arm type
    		 Experimental

    Investigational medicinal product name
    TAK-981
    Investigational medicinal product code
    Other name
    Subasumstat
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    TAK-981 40 mg, IV infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle.

    Investigational medicinal product name
    Pembrolizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months.

    Arm title
    		 Dose Expansion: Cohort B: Cervical Cancer
    Arm description
    		 Participants with cervical cancer received TAK-981 as IV infusion on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle up to disease progression or 24-months and pembrolizumab 200 mg IV infusion as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months.
    Arm type
    		 Experimental

    Investigational medicinal product name
    TAK-981
    Investigational medicinal product code
    Other name
    Subasumstat
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    TAK-981 40 mg, IV infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle.

    Investigational medicinal product name
    Pembrolizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months.

    Arm title
    		 Dose Expansion: Cohort C: MSS-CRC
    Arm description
    		 Participants with MSS-CRC received TAK-981 as IV infusion on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle up to disease progression or 24-months and pembrolizumab 200 mg IV infusion as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months.
    Arm type
    		 Experimental

    Investigational medicinal product name
    TAK-981
    Investigational medicinal product code
    Other name
    Subasumstat
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    TAK-981 40 mg, IV infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle.

    Investigational medicinal product name
    Pembrolizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months.

    Arm title
    		 Dose Expansion: Cohort D: Cutaneous Melanoma
    Arm description
    		 Participants with cutaneous melanoma received TAK-981 as IV infusion on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle up to disease progression or 24-months and pembrolizumab 200 mg IV infusion as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months.
    Arm type
    		 Experimental

    Investigational medicinal product name
    TAK-981
    Investigational medicinal product code
    Other name
    Subasumstat
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    TAK-981 40 mg, IV infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle.

    Investigational medicinal product name
    Pembrolizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months.

    Arm title
    		 Dose Expansion: Cohort E: Squamous NSCLC
    Arm description
    		 Participants with squamous NSCLC received TAK-981 as IV infusion on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle up to disease progression or 24-months and pembrolizumab 200 mg IV infusion as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months.
    Arm type
    		 Experimental

    Investigational medicinal product name
    TAK-981
    Investigational medicinal product code
    Other name
    Subasumstat
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    TAK-981 40 mg, IV infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle.

    Investigational medicinal product name
    Pembrolizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months.

    Arm title
    		 Dose Expansion: Cohort F: CPI Refractory Squamous or NSCLC
    Arm description
    		 Participants with CPI refractory squamous or non-squamous NSCLC received TAK-981 as IV infusion on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle up to disease progression or 24-months and pembrolizumab 200 mg IV infusion as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months.
    Arm type
    		 Experimental

    Investigational medicinal product name
    TAK-981
    Investigational medicinal product code
    Other name
    Subasumstat
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    TAK-981 40 mg, IV infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle.

    Investigational medicinal product name
    Pembrolizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months.

    Number of subjects in period 2
    		Dose Expansion: Cohort A: Non-squamous NSCLC TAK-981 90 mg Dose Expansion: Cohort A: Non-squamous NSCLC TAK-981 120 mg Dose Expansion: Cohort B: Cervical Cancer Dose Expansion: Cohort C: MSS-CRC Dose Expansion: Cohort D: Cutaneous Melanoma Dose Expansion: Cohort E: Squamous NSCLC Dose Expansion: Cohort F: CPI Refractory Squamous or NSCLC
    Started
    14
    9
    21
    9
    28
    15
    4
    Completed
    8
    5
    17
    2
    23
    4
    1
    Not completed
    6
    4
    4
    7
    5
    11
    3
         Consent withdrawn by subject
    1
    2
    4
    2
    1
    4
    1
         Reason Not Specified
    -
    -
    -
    1
    -
    -
    -
         Progressive Disease
    2
    1
    -
    3
    3
    4
    2
         New anti-cancer therapy
    3
    1
    -
    -
    -
    2
    -
         Lost to follow-up
    -
    -
    -
    1
    1
    1
    -

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Dose Escalation: TAK-981 40 mg + Pembrolizumab
    Reporting group description
    		 Participants received TAK-981 40 mg, IV infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle and pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle until the RP2D was determined (for a maximum of 24 months).

    Reporting group title
    Dose Escalation: TAK-981 60 mg + Pembrolizumab
    Reporting group description
    		 Participants received TAK-981 60 mg, IV infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle and pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle until the RP2D was determined (for a maximum of 24 months).

    Reporting group title
    Dose Escalation: TAK-981 90 mg + Pembrolizumab
    Reporting group description
    		 Participants received TAK-981 90 mg, IV infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle and pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle until the RP2D was determined (for a maximum of 24 months).

    Reporting group title
    Dose Escalation: TAK-981 120 mg + Pembrolizumab
    Reporting group description
    		 Participants received TAK-981, 120 mg, IV infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle and pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle until the RP2D was determined (for a maximum of 24 months).

    Reporting group values
    		 Dose Escalation: TAK-981 40 mg + Pembrolizumab Dose Escalation: TAK-981 60 mg + Pembrolizumab Dose Escalation: TAK-981 90 mg + Pembrolizumab Dose Escalation: TAK-981 120 mg + Pembrolizumab Total
    Number of subjects
    		 3 6 33 19
    Age Categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 66.0 ( 5.57 ) 53.5 ( 7.23 ) 56.2 ( 11.91 ) 59.8 ( 13.32 ) -
    Gender categorical
    Units: Subjects
        Female
    		 1 5 16 8 30
        Male
    		 2 1 17 11 31
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    		 0 0 0 0 0
        Asian
    		 0 4 8 7 19
        Native Hawaiian or Other Pacific Islander
    		 0 0 0 0 0
        Black or African American
    		 0 0 3 1 4
        White
    		 3 2 17 9 31
        More than one race
    		 0 0 0 0 0
        Unknown or Not Reported
    		 0 0 5 2 7
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 2 1 6 1 10
        Not Hispanic or Latino
    		 1 5 25 18 49
        Unknown or Not Reported
    		 0 0 2 0 2
    Subject analysis sets

    Subject analysis set title
    Dose Expansion: Cohort A: Non-squamous NSCLC TAK-981 90 mg
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Participants with non-squamous NSCLC received TAK-981 as IV infusion on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle up to disease progression or 24-months and pembrolizumab 200 mg IV infusion as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months.

    Subject analysis set title
    Dose Expansion: Cohort A: Non-squamous NSCLC TAK-981 120 mg
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Participants with non-squamous NSCLC received TAK-981 as IV infusion on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle up to disease progression or 24-months and pembrolizumab 200 mg IV infusion as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months.

    Subject analysis set title
    Dose Expansion: Cohort B: Cervical Cancer
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Participants with cervical cancer received TAK-981 as IV infusion on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle up to disease progression or 24-months and pembrolizumab 200 mg IV infusion as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months.

    Subject analysis set title
    Dose Expansion: Cohort C: MSS-CRC
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Participants with MSS-CRC received TAK-981 as IV infusion on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle up to disease progression or 24-months and pembrolizumab 200 mg IV infusion as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months.

    Subject analysis set title
    Dose Expansion: Cohort D: Cutaneous Melanoma
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Participants with cutaneous melanoma received TAK-981 as IV infusion on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle up to disease progression or 24-months and pembrolizumab 200 mg IV infusion as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months.

    Subject analysis set title
    Dose Expansion: Cohort E: Squamous NSCLC
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Participants with squamous NSCLC received TAK-981 as IV infusion on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle up to disease progression or 24-months and pembrolizumab 200 mg IV infusion as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months.

    Subject analysis set title
    Dose Expansion: Cohort F: CPI Refractory Squamous or NSCLC
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Participants with CPI refractory squamous or non-squamous NSCLC received TAK-981 as IV infusion on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle up to disease progression or 24-months and pembrolizumab 200 mg IV infusion as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months.

    Subject analysis sets values
    		 Dose Expansion: Cohort A: Non-squamous NSCLC TAK-981 90 mg Dose Expansion: Cohort A: Non-squamous NSCLC TAK-981 120 mg Dose Expansion: Cohort B: Cervical Cancer Dose Expansion: Cohort C: MSS-CRC Dose Expansion: Cohort D: Cutaneous Melanoma Dose Expansion: Cohort E: Squamous NSCLC Dose Expansion: Cohort F: CPI Refractory Squamous or NSCLC
    Number of subjects
    14
    9
    21
    9
    28
    15
    4
    Age Categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    63.3 ( 10.83 )
    68.7 ( 9.12 )
    51.8 ( 13.24 )
    49.6 ( 9.22 )
    55.9 ( 13.95 )
    67.5 ( 7.66 )
    73.5 ( 3.70 )
    Gender categorical
    Units: Subjects
        Female
    6
    5
    21
    5
    12
    1
    1
        Male
    8
    4
    0
    4
    16
    14
    3
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    0
    0
    0
    0
    0
    0
    0
        Asian
    3
    1
    2
    1
    4
    5
    0
        Native Hawaiian or Other Pacific Islander
    0
    0
    0
    0
    0
    0
    0
        Black or African American
    1
    0
    0
    1
    0
    0
    0
        White
    10
    8
    17
    7
    23
    10
    4
        More than one race
    0
    0
    2
    0
    0
    0
    0
        Unknown or Not Reported
    0
    0
    0
    0
    1
    0
    0
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    5
    0
    12
    0
    14
    0
    0
        Not Hispanic or Latino
    8
    9
    9
    9
    14
    14
    4
        Unknown or Not Reported
    1
    0
    0
    0
    0
    1
    0

    End points

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    End points reporting groups
    Reporting group title
    Dose Escalation: TAK-981 40 mg + Pembrolizumab
    Reporting group description
    		 Participants received TAK-981 40 mg, IV infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle and pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle until the RP2D was determined (for a maximum of 24 months).

    Reporting group title
    Dose Escalation: TAK-981 60 mg + Pembrolizumab
    Reporting group description
    		 Participants received TAK-981 60 mg, IV infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle and pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle until the RP2D was determined (for a maximum of 24 months).

    Reporting group title
    Dose Escalation: TAK-981 90 mg + Pembrolizumab
    Reporting group description
    		 Participants received TAK-981 90 mg, IV infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle and pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle until the RP2D was determined (for a maximum of 24 months).

    Reporting group title
    Dose Escalation: TAK-981 120 mg + Pembrolizumab
    Reporting group description
    		 Participants received TAK-981, 120 mg, IV infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle and pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle until the RP2D was determined (for a maximum of 24 months).
    Reporting group title
    Dose Expansion: Cohort A: Non-squamous NSCLC TAK-981 90 mg
    Reporting group description
    		 Participants with non-squamous NSCLC received TAK-981 as IV infusion on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle up to disease progression or 24-months and pembrolizumab 200 mg IV infusion as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months.

    Reporting group title
    Dose Expansion: Cohort A: Non-squamous NSCLC TAK-981 120 mg
    Reporting group description
    		 Participants with non-squamous NSCLC received TAK-981 as IV infusion on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle up to disease progression or 24-months and pembrolizumab 200 mg IV infusion as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months.

    Reporting group title
    Dose Expansion: Cohort B: Cervical Cancer
    Reporting group description
    		 Participants with cervical cancer received TAK-981 as IV infusion on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle up to disease progression or 24-months and pembrolizumab 200 mg IV infusion as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months.

    Reporting group title
    Dose Expansion: Cohort C: MSS-CRC
    Reporting group description
    		 Participants with MSS-CRC received TAK-981 as IV infusion on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle up to disease progression or 24-months and pembrolizumab 200 mg IV infusion as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months.

    Reporting group title
    Dose Expansion: Cohort D: Cutaneous Melanoma
    Reporting group description
    		 Participants with cutaneous melanoma received TAK-981 as IV infusion on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle up to disease progression or 24-months and pembrolizumab 200 mg IV infusion as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months.

    Reporting group title
    Dose Expansion: Cohort E: Squamous NSCLC
    Reporting group description
    		 Participants with squamous NSCLC received TAK-981 as IV infusion on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle up to disease progression or 24-months and pembrolizumab 200 mg IV infusion as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months.

    Reporting group title
    Dose Expansion: Cohort F: CPI Refractory Squamous or NSCLC
    Reporting group description
    		 Participants with CPI refractory squamous or non-squamous NSCLC received TAK-981 as IV infusion on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle up to disease progression or 24-months and pembrolizumab 200 mg IV infusion as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months.

    Subject analysis set title
    Dose Expansion: Cohort A: Non-squamous NSCLC TAK-981 90 mg
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Participants with non-squamous NSCLC received TAK-981 as IV infusion on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle up to disease progression or 24-months and pembrolizumab 200 mg IV infusion as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months.

    Subject analysis set title
    Dose Expansion: Cohort A: Non-squamous NSCLC TAK-981 120 mg
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Participants with non-squamous NSCLC received TAK-981 as IV infusion on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle up to disease progression or 24-months and pembrolizumab 200 mg IV infusion as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months.

    Subject analysis set title
    Dose Expansion: Cohort B: Cervical Cancer
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Participants with cervical cancer received TAK-981 as IV infusion on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle up to disease progression or 24-months and pembrolizumab 200 mg IV infusion as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months.

    Subject analysis set title
    Dose Expansion: Cohort C: MSS-CRC
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Participants with MSS-CRC received TAK-981 as IV infusion on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle up to disease progression or 24-months and pembrolizumab 200 mg IV infusion as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months.

    Subject analysis set title
    Dose Expansion: Cohort D: Cutaneous Melanoma
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Participants with cutaneous melanoma received TAK-981 as IV infusion on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle up to disease progression or 24-months and pembrolizumab 200 mg IV infusion as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months.

    Subject analysis set title
    Dose Expansion: Cohort E: Squamous NSCLC
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Participants with squamous NSCLC received TAK-981 as IV infusion on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle up to disease progression or 24-months and pembrolizumab 200 mg IV infusion as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months.

    Subject analysis set title
    Dose Expansion: Cohort F: CPI Refractory Squamous or NSCLC
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Participants with CPI refractory squamous or non-squamous NSCLC received TAK-981 as IV infusion on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle up to disease progression or 24-months and pembrolizumab 200 mg IV infusion as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months.

    Primary: Phase 1: Number of Participants With One or More Treatment Emergent Adverse Events (TEAEs)

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    End point title
    		 Phase 1: Number of Participants With One or More Treatment Emergent Adverse Events (TEAEs) [1]
    End point description
    An adverse event (AE) is any untoward medical occurrence in a participant administered a medicinal investigational drug. The untoward medical occurrence does not necessarily have to have a causal relationship with treatment. A TEAE is defined as an AE that occurs after administration of first dose of study drug and through 30 days after last dose of study drug or until start of subsequent antineoplastic therapy. AEs were evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 5.0 except cytokine release syndrome (CRS), which was graded according to American Society for Transplantation and Cellular Therapy (ASTCT) Consensus Grading for CRS. Safety Analysis Set included participants who received at least 1 dose, even if incomplete, of study drug.
    End point type
    Primary
    End point timeframe
    Up to approximately 24 months
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive analysis were planned for this endpoint.
    End point values
    		 Dose Escalation: TAK-981 40 mg + Pembrolizumab Dose Escalation: TAK-981 60 mg + Pembrolizumab Dose Escalation: TAK-981 90 mg + Pembrolizumab Dose Escalation: TAK-981 120 mg + Pembrolizumab
    Number of subjects analysed
    3
    6
    33
    19
    Units: participants
    3
    6
    33
    19
    No statistical analyses for this end point

    Primary: Phase 1: Number of Participants With One or More Serious Adverse Events (SAEs)

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    End point title
    		 Phase 1: Number of Participants With One or More Serious Adverse Events (SAEs) [2]
    End point description
    An SAE is any untoward medical occurrence that results in death; is life-threatening; requires inpatient hospitalization or prolongation of present hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect or is a medically important event that may not be immediately life-threatening or result in death or hospitalization, but may jeopardize the participant or may require intervention to prevent one of other outcomes listed in definition above, or involves suspected transmission via a medicinal product of an infectious agent. Safety Analysis Set included participants who received at least 1 dose, even if incomplete, of study drug.
    End point type
    Primary
    End point timeframe
    Up to approximately 24 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: Only descriptive analysis were planned for this endpoint.
    End point values
    		 Dose Escalation: TAK-981 40 mg + Pembrolizumab Dose Escalation: TAK-981 60 mg + Pembrolizumab Dose Escalation: TAK-981 90 mg + Pembrolizumab Dose Escalation: TAK-981 120 mg + Pembrolizumab
    Number of subjects analysed
    3
    6
    33
    19
    Units: participants
    0
    3
    17
    10
    No statistical analyses for this end point

    Primary: Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs)

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    End point title
    		 Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) [3]
    End point description
    DLTs were evaluated according to NCI CTCAE Version 5.0 except CRS, which was graded according to ASTCT Consensus Grading for CRS. The DLT-evaluable Analysis Set included participants enrolled in Phase 1b of the study and who experienced a DLT at any time after receiving the first dose of TAK-981 during the DLT assessment period (Cycle 1) or who received all planned TAK-981 doses and 1 administration of pembrolizumab in Cycle 1.
    End point type
    Primary
    End point timeframe
    Up to Cycle 1 (each cycle was of 21 days)
    Notes
    [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive analysis were planned for this endpoint.
    End point values
    		 Dose Escalation: TAK-981 40 mg + Pembrolizumab Dose Escalation: TAK-981 60 mg + Pembrolizumab Dose Escalation: TAK-981 90 mg + Pembrolizumab Dose Escalation: TAK-981 120 mg + Pembrolizumab
    Number of subjects analysed
    3
    6
    30
    19
    Units: participants
    0
    0
    2
    1
    No statistical analyses for this end point

    Primary: Phase 1: Number of Participants With Grade 3 or Higher Treatment Emergent Adverse Events (TEAEs)

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    End point title
    		 Phase 1: Number of Participants With Grade 3 or Higher Treatment Emergent Adverse Events (TEAEs) [4]
    End point description
    AE means any untoward medical occurrence in a participant administered a pharmaceutical product. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product whether or not it is related to the medicinal product. A TEAE was defined as an adverse event which occurred on or after the first dose of study drug and no more than 30 days after the last dose of study drug. A severity grade was evaluated as per the NCI CTCAE Version 5.0, except for CRS, which was assessed by ASTCT Consensus Grading for CRS.DLTs were evaluated according to NCI CTCAE Version 5.0 except CRS, which was graded according to ASTCT Consensus Grading for CRS. Safety Analysis Set included participants who received at least 1 dose, even if incomplete, of study drug. Reporting Groups
    End point type
    Primary
    End point timeframe
    Up to approximately 24 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: Only descriptive analysis were planned for this endpoint.
    End point values
    		 Dose Escalation: TAK-981 40 mg + Pembrolizumab Dose Escalation: TAK-981 60 mg + Pembrolizumab Dose Escalation: TAK-981 90 mg + Pembrolizumab Dose Escalation: TAK-981 120 mg + Pembrolizumab
    Number of subjects analysed
    3
    6
    33
    19
    Units: participants
    0
    2
    20
    15
    No statistical analyses for this end point

    Primary: Phase 2: Overall Response Rate (ORR) as Assessed by the Investigator According to RECIST, Version 1.1

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    End point title
    		 Phase 2: Overall Response Rate (ORR) as Assessed by the Investigator According to RECIST, Version 1.1 [5]
    End point description
    ORR is defined as the percentage of participants who achieve Complete Response (CR) and Partial Response (PR) (determined by the investigator) during the study according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1. Response-Evaluable Analysis Set included participants who had received at least 1 dose of study drug, had sites of measurable disease at baseline, and 1 postbaseline disease assessment, or were discontinued due to symptomatic deterioration or death before a postbaseline evaluation happened.
    End point type
    Primary
    End point timeframe
    Up to approximately 25 months
    Notes
    [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive analysis were planned for this endpoint.
    End point values
    		 Dose Expansion: Cohort A: Non-squamous NSCLC TAK-981 90 mg Dose Expansion: Cohort A: Non-squamous NSCLC TAK-981 120 mg Dose Expansion: Cohort B: Cervical Cancer Dose Expansion: Cohort C: MSS-CRC Dose Expansion: Cohort D: Cutaneous Melanoma Dose Expansion: Cohort E: Squamous NSCLC Dose Expansion: Cohort F: CPI Refractory Squamous or NSCLC
    Number of subjects analysed
    10
    8
    20
    9
    28
    13
    4
    Units: percentage of participants
        number (confidence interval 95%)
    20 (2.52 to 55.61)
    0 (0.00 to 36.94)
    30 (11.89 to 54.28)
    0 (0.00 to 33.63)
    25 (10.69 to 44.87)
    7.7 (0.19 to 36.03)
    0 (0.00 to 60.24)
    No statistical analyses for this end point

    Primary: Phase 1: Number of Participants with One or More TEAEs Leading to Dose Modifications and Treatment Discontinuation

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    End point title
    		 Phase 1: Number of Participants with One or More TEAEs Leading to Dose Modifications and Treatment Discontinuation [6]
    End point description
    An AE is any untoward medical occurrence in a participant administered a medicinal investigational drug. The untoward medical occurrence does not necessarily have to have a causal relationship with treatment. A TEAE is defined as an AE that occurs after administration of first dose of study drug and through 30 days after last dose of study drug or until start of subsequent antineoplastic therapy. Pembrolizumab is denoted as Pem. Safety Analysis Set included participants who received at least 1 dose, even if incomplete, of study drug.
    End point type
    Primary
    End point timeframe
    Up to approximately 24 months
    Notes
    [6] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive analysis were planned for this endpoint.
    End point values
    		 Dose Escalation: TAK-981 40 mg + Pembrolizumab Dose Escalation: TAK-981 60 mg + Pembrolizumab Dose Escalation: TAK-981 90 mg + Pembrolizumab Dose Escalation: TAK-981 120 mg + Pembrolizumab
    Number of subjects analysed
    3
    6
    33
    19
    Units: participants
        TEAE Resulting in Dose Modifications of TAK-981
    0
    3
    22
    11
        TEAE Resulting in Dose Modifications of Pem
    0
    3
    15
    4
        TEAE Resulting in Drug Discontinuation of TAK-981
    0
    1
    3
    2
        TEAE Resulting in Drug Discontinuation of Pem
    0
    1
    4
    1
    No statistical analyses for this end point

    Primary: Phase 1: Number of Participants With Clinically Significant Laboratory Values

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    End point title
    		 Phase 1: Number of Participants With Clinically Significant Laboratory Values [7]
    End point description
    Laboratory parameters included clinical chemistry, hematology, and urinalysis. Participants with at least 1 Grade 3 or 4 Lab Abnormalities were reported. Safety Analysis Set included participants who received at least 1 dose, even if incomplete, of study drug.
    End point type
    Primary
    End point timeframe
    Up to approximately 24 months
    Notes
    [7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive analysis were planned for this endpoint.
    End point values
    		 Dose Escalation: TAK-981 40 mg + Pembrolizumab Dose Escalation: TAK-981 60 mg + Pembrolizumab Dose Escalation: TAK-981 90 mg + Pembrolizumab Dose Escalation: TAK-981 120 mg + Pembrolizumab
    Number of subjects analysed
    3
    6
    33
    19
    Units: participants
        Hematology
    1
    3
    7
    6
        Serum Chemistry
    1
    1
    7
    5
        Coagulation
    0
    0
    0
    1
    No statistical analyses for this end point

    Secondary: Phase 1: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-981

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    End point title
    		 Phase 1: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-981
    End point description
    PK Analysis Set included participants with sufficient dosing and PK data to reliably estimate 1 or more PK parameters. 'n' denotes number of participants available for analysis during the specified time-point.
    End point type
    Secondary
    End point timeframe
    Cycle 1 (each cycle is 21 days) Days 1 and 8 pre-dose and at multiple timepoints (up to 24 hours)
    End point values
    		 Dose Escalation: TAK-981 40 mg + Pembrolizumab Dose Escalation: TAK-981 60 mg + Pembrolizumab Dose Escalation: TAK-981 90 mg + Pembrolizumab Dose Escalation: TAK-981 120 mg + Pembrolizumab
    Number of subjects analysed
    3
    6
    33
    19
    Units: hours
    median (full range (min-max))
        Cycle 1 Day 1(n=3,6,33,19)
    1.22 (1.20 to 1.23)
    1.27 (1.00 to 1.47)
    1.17 (1.00 to 1.88)
    1.20 (1.00 to 1.72)
        Cycle 1 Day 8(n=3,6,30,17)
    1.18 (1.17 to 1.25)
    1.41 (1.00 to 1.70)
    1.22 (1.00 to 3.10)
    1.28 (0.98 to 1.50)
    No statistical analyses for this end point

    Secondary: Phase 1: Cmax: Maximum Observed Plasma Concentration for TAK-981

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    End point title
    		 Phase 1: Cmax: Maximum Observed Plasma Concentration for TAK-981
    End point description
    Pharmacokinetic (PK) Analysis Set included participants with sufficient dosing and PK data to reliably estimate 1 or more PK parameters. 'n' denotes number of participants available for analysis during the specified time-point.
    End point type
    Secondary
    End point timeframe
    Cycle 1 (each cycle is 21 days) Days 1 and 8 pre-dose and at multiple timepoints (up to 24 hours)
    End point values
    		 Dose Escalation: TAK-981 40 mg + Pembrolizumab Dose Escalation: TAK-981 60 mg + Pembrolizumab Dose Escalation: TAK-981 90 mg + Pembrolizumab Dose Escalation: TAK-981 120 mg + Pembrolizumab
    Number of subjects analysed
    3
    6
    33
    19
    Units: nanograms per milliliter (ng/ml)
    arithmetic mean (standard deviation)
        Cycle 1 Day 1(n=3,6,33,19)
    335 ( 282 )
    728 ( 396 )
    888 ( 423 )
    1290 ( 571 )
        Cycle 1 Day 8(n=3,6,30,17)
    280 ( 167 )
    448 ( 206 )
    780 ( 524 )
    1270 ( 770 )
    No statistical analyses for this end point

    Secondary: Phase 1: AUC0-t: Area Under the Plasma Concentration-time Curve from Time 0 to Time t Over the Dosing Interval for TAK-981

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    End point title
    		 Phase 1: AUC0-t: Area Under the Plasma Concentration-time Curve from Time 0 to Time t Over the Dosing Interval for TAK-981
    End point description
    PK Analysis Set included participants with sufficient dosing and PK data to reliably estimate 1 or more PK parameters. Subjects analyzed is the number of participants with data available for analysis. 'n' denotes number of participants available for analysis during the specified time-point.
    End point type
    Secondary
    End point timeframe
    Cycle 1 (each cycle is 21 days) Days 1 and 8 pre-dose and at multiple timepoints (up to 24 hours)
    End point values
    		 Dose Escalation: TAK-981 40 mg + Pembrolizumab Dose Escalation: TAK-981 60 mg + Pembrolizumab Dose Escalation: TAK-981 90 mg + Pembrolizumab Dose Escalation: TAK-981 120 mg + Pembrolizumab
    Number of subjects analysed
    3
    6
    32
    18
    Units: hours*ng/mL
    arithmetic mean (standard deviation)
        Cycle 1 Day 1(n=3,6,32,18)
    880 ( 427 )
    1370 ( 517 )
    1950 ( 735 )
    2580 ( 949 )
        Cycle 1 Day 8(n=3,5,28,16)
    814 ( 290 )
    976 ( 232 )
    1780 ( 908 )
    2640 ( 1260 )
    No statistical analyses for this end point

    Secondary: Phase 1: AUC∞: Area Under the Plasma Concentration-time Curve from Time 0 to Infinity for TAK-981

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    End point title
    		 Phase 1: AUC∞: Area Under the Plasma Concentration-time Curve from Time 0 to Infinity for TAK-981
    End point description
    PK Analysis Set included participants with sufficient dosing and PK data to reliably estimate 1 or more PK parameters. Subjects analyzed is the number of participants with data available for analysis. 'n' denotes number of participants available for analysis during the specified time-point.
    End point type
    Secondary
    End point timeframe
    Cycle 1 (each cycle is 21 days) Days 1 and 8 pre-dose and at multiple timepoints (up to 24 hours)
    End point values
    		 Dose Escalation: TAK-981 40 mg + Pembrolizumab Dose Escalation: TAK-981 60 mg + Pembrolizumab Dose Escalation: TAK-981 90 mg + Pembrolizumab Dose Escalation: TAK-981 120 mg + Pembrolizumab
    Number of subjects analysed
    3
    6
    32
    17
    Units: hours*ng/mL
    arithmetic mean (standard deviation)
        Cycle 1 Day 1(n=3,6,32,17)
    909 ( 432 )
    1400 ( 530 )
    2020 ( 760 )
    2660 ( 1020 )
        Cycle 1 Day 8(n=3,5,27,16)
    845 ( 292 )
    1010 ( 233 )
    1830 ( 942 )
    2750 ( 1320 )
    No statistical analyses for this end point

    Secondary: Phase 1: CL: Total Clearance After Intravenous Administration for TAK-981

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    End point title
    		 Phase 1: CL: Total Clearance After Intravenous Administration for TAK-981
    End point description
    PK Analysis Set included participants with sufficient dosing and PK data to reliably estimate 1 or more PK parameters. Subjects analyzed is the number of participants with data available for analysis. 'n' denotes number of participants available for analysis during the specified time-point.
    End point type
    Secondary
    End point timeframe
    Cycle 1 (each cycle is 21 days) Days 1 and 8 pre-dose and at multiple timepoints (up to 24 hours)
    End point values
    		 Dose Escalation: TAK-981 40 mg + Pembrolizumab Dose Escalation: TAK-981 60 mg + Pembrolizumab Dose Escalation: TAK-981 90 mg + Pembrolizumab Dose Escalation: TAK-981 120 mg + Pembrolizumab
    Number of subjects analysed
    3
    6
    32
    17
    Units: liters per hour (L/h)
    arithmetic mean (standard deviation)
        Cycle 1 Day 1(n=3,6,32,17)
    51.1 ( 23.2 )
    47.2 ( 14.8 )
    51.3 ( 19.6 )
    51.0 ( 18.4 )
        Cycle 1 Day 8(n=3,5,27,16)
    51.7 ( 19.3 )
    62.5 ( 15.5 )
    57.0 ( 21.8 )
    53.8 ( 26.8 )
    No statistical analyses for this end point

    Secondary: Phase 1: t1/2z: Terminal Disposition Phase Half-life for TAK-981

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    End point title
    		 Phase 1: t1/2z: Terminal Disposition Phase Half-life for TAK-981
    End point description
    PK Analysis Set included participants with sufficient dosing and PK data to reliably estimate 1 or more PK parameters. Subjects analyzed is the number of participants with data available for analysis. 'n' denotes number of participants available for analysis during the specified time-point.
    End point type
    Secondary
    End point timeframe
    Cycle 1 (each cycle is 21 days) Days 1 and 8 pre-dose and at multiple timepoints (up to 24 hours)
    End point values
    		 Dose Escalation: TAK-981 40 mg + Pembrolizumab Dose Escalation: TAK-981 60 mg + Pembrolizumab Dose Escalation: TAK-981 90 mg + Pembrolizumab Dose Escalation: TAK-981 120 mg + Pembrolizumab
    Number of subjects analysed
    3
    6
    32
    17
    Units: hours
    median (full range (min-max))
        Cycle 1 Day 1(n=3,6,32,17)
    5.88 (5.82 to 6.16)
    5.58 (5.04 to 6.03)
    5.72 (3.31 to 10.43)
    6.79 (5.93 to 8.14)
        Cycle 1 Day 8(n=3,5,27,16)
    5.83 (5.69 to 6.33)
    5.68 (5.22 to 6.44)
    6.06 (4.18 to 9.13)
    6.67 (5.26 to 8.08)
    No statistical analyses for this end point

    Secondary: Phase 1: Vss: Volume of Distribution at Steady State After Intravenous Administration for TAK-981

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    End point title
    		 Phase 1: Vss: Volume of Distribution at Steady State After Intravenous Administration for TAK-981
    End point description
    PK Analysis Set included participants with sufficient dosing and PK data to reliably estimate 1 or more PK parameters. Subjects analyzed is the number of participants with data available for analysis. 'n' denotes number of participants available for analysis during the specified time-point.
    End point type
    Secondary
    End point timeframe
    Cycle 1 (each cycle is 21 days) Days 1 and 8 pre-dose and at multiple timepoints (up to 24 hours)
    End point values
    		 Dose Escalation: TAK-981 40 mg + Pembrolizumab Dose Escalation: TAK-981 60 mg + Pembrolizumab Dose Escalation: TAK-981 90 mg + Pembrolizumab Dose Escalation: TAK-981 120 mg + Pembrolizumab
    Number of subjects analysed
    3
    6
    32
    17
    Units: liters (L)
    arithmetic mean (standard deviation)
        Cycle 1 Day 1(n=3,6,32,17)
    312 ( 203 )
    181 ( 56.9 )
    240 ( 115 )
    240 ( 98.5 )
        Cycle 1 Day 8(n=3,5,27,16)
    323 ( 178 )
    314 ( 109 )
    300 ( 129 )
    271 ( 150 )
    No statistical analyses for this end point

    Secondary: Phases 1 and 2: Disease Control Rate (DCR)

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    End point title
    		 Phases 1 and 2: Disease Control Rate (DCR)
    End point description
    DCR is defined as the percentage of participants who achieved stable disease (SD) or better (CR + PR + SD determined by the investigator) >6 weeks during the trial in the response-evaluable population. Response-Evaluable Analysis Set included participants who had received at least 1 dose of study drug, had sites of measurable disease at baseline, and 1 postbaseline disease assessment, or were discontinued due to symptomatic deterioration or death before a postbaseline evaluation happened.
    End point type
    Secondary
    End point timeframe
    Phase 1: Up to approximately 24 months, Phase 2: Up to approximately 25 months
    End point values
    		 Dose Escalation: TAK-981 40 mg + Pembrolizumab Dose Expansion: Cohort A: Non-squamous NSCLC TAK-981 90 mg Dose Escalation: TAK-981 60 mg + Pembrolizumab Dose Expansion: Cohort A: Non-squamous NSCLC TAK-981 120 mg Dose Escalation: TAK-981 90 mg + Pembrolizumab Dose Expansion: Cohort B: Cervical Cancer Dose Escalation: TAK-981 120 mg + Pembrolizumab Dose Expansion: Cohort C: MSS-CRC Dose Expansion: Cohort D: Cutaneous Melanoma Dose Expansion: Cohort E: Squamous NSCLC Dose Expansion: Cohort F: CPI Refractory Squamous or NSCLC
    Number of subjects analysed
    3
    10
    6
    8
    33
    20
    18
    9
    28
    13
    4
    Units: percentage of participants
        number (confidence interval 95%)
    33.3 (0.84 to 90.57)
    80.0 (44.39 to 97.48)
    50.0 (11.81 to 88.19)
    62.5 (24.49 to 91.48)
    30.3 (15.59 to 48.71)
    55.0 (31.53 to 76.94)
    44.4 (21.53 to 69.24)
    22.2 (2.81 to 60.01)
    67.9 (47.65 to 84.12)
    30.8 (9.09 to 61.43)
    0 (0.00 to 60.24)
    No statistical analyses for this end point

    Secondary: Phases 1 and 2: Durable Response Rate (DRR)

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    End point title
    		 Phases 1 and 2: Durable Response Rate (DRR)
    End point description
    DRR is defined as the rate of objective responses (CR + PR) maintained for at least 6 months initiating at any time within 12 months of commencing therapy. Response-Evaluable Analysis Set included participants who had received at least 1 dose of study drug, had sites of measurable disease at baseline, and 1 postbaseline disease assessment, or were discontinued due to symptomatic deterioration or death before a postbaseline evaluation happened.
    End point type
    Secondary
    End point timeframe
    Phase 1: Up to approximately 24 months, Phase 2: Up to approximately 25 months
    End point values
    		 Dose Escalation: TAK-981 40 mg + Pembrolizumab Dose Expansion: Cohort A: Non-squamous NSCLC TAK-981 90 mg Dose Escalation: TAK-981 60 mg + Pembrolizumab Dose Expansion: Cohort A: Non-squamous NSCLC TAK-981 120 mg Dose Escalation: TAK-981 90 mg + Pembrolizumab Dose Expansion: Cohort B: Cervical Cancer Dose Escalation: TAK-981 120 mg + Pembrolizumab Dose Expansion: Cohort C: MSS-CRC Dose Expansion: Cohort D: Cutaneous Melanoma Dose Expansion: Cohort E: Squamous NSCLC Dose Expansion: Cohort F: CPI Refractory Squamous or NSCLC
    Number of subjects analysed
    3
    10
    6
    8
    33
    20
    18
    9
    28
    13
    4
    Units: percentage of participants
        number (confidence interval 95%)
    0 (0.00 to 70.76)
    10.0 (0.25 to 44.50)
    16.7 (0.42 to 64.12)
    0 (0.00 to 36.94)
    6.1 (0.74 to 20.23)
    0 (0.00 to 16.84)
    0 (0.00 to 18.53)
    0 (0.00 to 33.63)
    10.7 (2.27 to 28.23)
    0 (0.00 to 24.71)
    0 (0.00 to 60.24)
    No statistical analyses for this end point

    Secondary: Phases 1 and 2: Duration of Response (DOR)

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    End point title
    		 Phases 1 and 2: Duration of Response (DOR)
    End point description
    DOR is defined as a time from the time of first documentation of tumor response to the first recorded occurrence of disease progression (PD) or death from any cause (whichever occurs first), through end of study. Response-Evaluable Analysis Set included participants who had received at least 1 dose of study drug, had sites of measurable disease at baseline, and 1 postbaseline disease assessment, or were discontinued due to symptomatic deterioration or death before a postbaseline evaluation happened. Subjects analysed is the number of participants with events. '-999' and '999' denotes lower and upper limit of 95% Confidence Interval (CI) was not estimable for a single participant. '99999' denotes upper limit of 95% CI was not estimable due to censoring. '9999' denotes median and upper limit of 95% CI was not estimable due to censoring.
    End point type
    Secondary
    End point timeframe
    Phase 1: Up to approximately 24 months, Phase 2: Up to approximately 25 months
    End point values
    		 Dose Escalation: TAK-981 40 mg + Pembrolizumab Dose Expansion: Cohort A: Non-squamous NSCLC TAK-981 90 mg Dose Escalation: TAK-981 60 mg + Pembrolizumab Dose Expansion: Cohort A: Non-squamous NSCLC TAK-981 120 mg Dose Escalation: TAK-981 90 mg + Pembrolizumab Dose Expansion: Cohort B: Cervical Cancer Dose Escalation: TAK-981 120 mg + Pembrolizumab Dose Expansion: Cohort C: MSS-CRC Dose Expansion: Cohort D: Cutaneous Melanoma Dose Expansion: Cohort E: Squamous NSCLC Dose Expansion: Cohort F: CPI Refractory Squamous or NSCLC
    Number of subjects analysed
    0 [8]
    1
    1
    0 [9]
    3
    2
    1
    0 [10]
    3
    1
    0 [11]
    Units: hours
        median (confidence interval 95%)
    ( to )
    7.62 (-999 to 999)
    17.12 (-999 to 999)
    ( to )
    7.39 (4.17 to 99999)
    9999 (4.67 to 9999)
    3.71 (-999 to 999)
    ( to )
    9999 (7.26 to 9999)
    4.34 (-999 to 999)
    ( to )
    Notes
    [8] - No participants with the event were available for analysis.
    [9] - No participants with events were available for analysis.
    [10] - No participants with events were available for analysis.
    [11] - No participants with events were available for analysis.
    No statistical analyses for this end point

    Secondary: Phases 1 and 2: Progression-free Survival (PFS)

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    End point title
    		 Phases 1 and 2: Progression-free Survival (PFS)
    End point description
    PFS is defined as time from the date of the first dose administration to the date of first documentation of PD or death due to any cause whichever occurs first, through the end of the study. Response-Evaluable Analysis Set included participants who had received at least 1 dose of study drug, had sites of measurable disease at baseline, and 1 postbaseline disease assessment, or were discontinued due to symptomatic deterioration or death before a postbaseline evaluation happened. Subjects analysed is the number of participants with events. '-999' and '999' denotes lower and upper limit of 95% CI was not estimable for a single participant. '99999' denotes upper limit of 95% CI was not estimable due to censoring.
    End point type
    Secondary
    End point timeframe
    Phase 1: Up to approximately 24 months, Phase 2: Up to approximately 25 months
    End point values
    		 Dose Escalation: TAK-981 40 mg + Pembrolizumab Dose Expansion: Cohort A: Non-squamous NSCLC TAK-981 90 mg Dose Escalation: TAK-981 60 mg + Pembrolizumab Dose Expansion: Cohort A: Non-squamous NSCLC TAK-981 120 mg Dose Escalation: TAK-981 90 mg + Pembrolizumab Dose Expansion: Cohort B: Cervical Cancer Dose Escalation: TAK-981 120 mg + Pembrolizumab Dose Expansion: Cohort C: MSS-CRC Dose Expansion: Cohort D: Cutaneous Melanoma Dose Expansion: Cohort E: Squamous NSCLC Dose Expansion: Cohort F: CPI Refractory Squamous or NSCLC
    Number of subjects analysed
    3
    8
    5
    7
    28
    15
    16
    8
    17
    11
    4
    Units: months
        median (confidence interval 95%)
    2.00 (2.00 to 99999)
    3.71 (3.29 to 9.20)
    4.21 (2.00 to 99999)
    4.59 (1.97 to 99999)
    1.99 (1.77 to 3.91)
    4.14 (2.14 to 8.87)
    2.11 (1.41 to 6.57)
    1.64 (1.28 to 2.00)
    8.97 (2.37 to 12.42)
    2.07 (1.87 to 2.30)
    1.28 (0.99 to 999)
    No statistical analyses for this end point

    Secondary: Phases 1 and 2: Time to Response (TTR)

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    End point title
    		 Phases 1 and 2: Time to Response (TTR)
    End point description
    TTR is defined as time from the date of the first dose administration to the date of first documented PR or better. Response-Evaluable Analysis Set included participants who had received at least 1 dose of study drug, had sites of measurable disease at baseline, and 1 postbaseline disease assessment, or were discontinued due to symptomatic deterioration or death before a postbaseline evaluation happened. Subjects analysed is the number of participants with events. '99999' denotes upper limit of 95% CI was not estimable due to censoring. '9999' denotes median and upper limit of 95% CI was not estimable due to censoring. '9999', '-9999' and '9999' denotes median, lower limit and upper limit of 95% CI was not estimable due to censoring.
    End point type
    Secondary
    End point timeframe
    Phase 1: Up to approximately 24 months, Phase 2: Up to approximately 25 months
    End point values
    		 Dose Escalation: TAK-981 40 mg + Pembrolizumab Dose Expansion: Cohort A: Non-squamous NSCLC TAK-981 90 mg Dose Escalation: TAK-981 60 mg + Pembrolizumab Dose Expansion: Cohort A: Non-squamous NSCLC TAK-981 120 mg Dose Escalation: TAK-981 90 mg + Pembrolizumab Dose Expansion: Cohort B: Cervical Cancer Dose Escalation: TAK-981 120 mg + Pembrolizumab Dose Expansion: Cohort C: MSS-CRC Dose Expansion: Cohort D: Cutaneous Melanoma Dose Expansion: Cohort E: Squamous NSCLC Dose Expansion: Cohort F: CPI Refractory Squamous or NSCLC
    Number of subjects analysed
    0 [12]
    2
    2
    0 [13]
    3
    6
    1
    0 [14]
    7
    1
    0 [15]
    Units: months
        median (confidence interval 95%)
    ( to )
    4.01 (3.98 to 99999)
    4.17 (1.91 to 99999)
    ( to )
    99999 (3.94 to 99999)
    6.01 (4.04 to 99999)
    9999 (-9999 to 9999)
    ( to )
    99999 (-99999 to 99999)
    99999 (-99999 to 99999)
    ( to )
    Notes
    [12] - No participants with the event were available for analysis.
    [13] - No participants with events were available for analysis.
    [14] - No participants with events were available for analysis.
    [15] - No participants with events were available for analysis.
    No statistical analyses for this end point

    Secondary: Phase 2: Overall Survival (OS)

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    End point title
    		 Phase 2: Overall Survival (OS)
    End point description
    OS is defined as the time from the date of the first dose administration to the date of death. Participants without documentation of death at the time of analysis were censored at the date last known to be alive. Response-Evaluable Analysis Set included participants who had received at least 1 dose of study drug, had sites of measurable disease at baseline, and 1 postbaseline disease assessment, or were discontinued due to symptomatic deterioration or death before a postbaseline evaluation happened. Subjects analysed is the number of participants with events. '99999' denotes upper limit of 95% CI was not estimable due to censoring. '9999' denotes median and upper limit of 95% CI was not estimable due to censoring. '9999', '-9999' and '9999' denotes median, lower limit and upper limit of 95% CI was not estimable due to censoring.
    End point type
    Secondary
    End point timeframe
    Up to approximately 25 months
    End point values
    		 Dose Expansion: Cohort A: Non-squamous NSCLC TAK-981 90 mg Dose Expansion: Cohort A: Non-squamous NSCLC TAK-981 120 mg Dose Expansion: Cohort B: Cervical Cancer Dose Expansion: Cohort C: MSS-CRC Dose Expansion: Cohort D: Cutaneous Melanoma Dose Expansion: Cohort E: Squamous NSCLC Dose Expansion: Cohort F: CPI Refractory Squamous or NSCLC
    Number of subjects analysed
    1
    4
    9
    2
    8
    1
    1
    Units: months
        median (confidence interval 95%)
    9999 (-9999 to 9999)
    10.12 (5.16 to 99999)
    14.55 (5.42 to 99999)
    9999 (4.21 to 9999)
    9999 (11.43 to 9999)
    9999 (-9999 to 9999)
    99999 (1.28 to 99999)
    No statistical analyses for this end point

    Secondary: Phases 1 and 2: Time to Progression (TTP)

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    End point title
    		 Phases 1 and 2: Time to Progression (TTP)
    End point description
    TTP is defined as the from the date of the first dose administration to the date of the first documentation of PD as defined by standard disease criteria. Response-Evaluable Analysis Set included participants who had received at least 1 dose of study drug, had sites of measurable disease at baseline, and 1 postbaseline disease assessment, or were discontinued due to symptomatic deterioration or death before a postbaseline evaluation happened. Subjects analysed is the number of participants with events. '99999' denotes upper limit of 95% CI was not estimable due to censoring.
    End point type
    Secondary
    End point timeframe
    Phase 1: Up to approximately 24 months, Phase 2: Up to approximately 25 months
    End point values
    		 Dose Escalation: TAK-981 40 mg + Pembrolizumab Dose Expansion: Cohort A: Non-squamous NSCLC TAK-981 90 mg Dose Escalation: TAK-981 60 mg + Pembrolizumab Dose Expansion: Cohort A: Non-squamous NSCLC TAK-981 120 mg Dose Escalation: TAK-981 90 mg + Pembrolizumab Dose Expansion: Cohort B: Cervical Cancer Dose Escalation: TAK-981 120 mg + Pembrolizumab Dose Expansion: Cohort C: MSS-CRC Dose Expansion: Cohort D: Cutaneous Melanoma Dose Expansion: Cohort E: Squamous NSCLC Dose Expansion: Cohort F: CPI Refractory Squamous or NSCLC
    Number of subjects analysed
    3
    8
    5
    6
    25
    13
    15
    6
    14
    11
    4
    Units: months
        median (confidence interval 95%)
    2.00 (2.00 to 99999)
    3.71 (3.29 to 9.20)
    4.21 (2.00 to 99999)
    4.01 (1.97 to 99999)
    2.07 (1.87 to 4.04)
    5.34 (2.20 to 8.87)
    2.07 (1.41 to 6.93)
    1.76 (1.28 to 99999)
    9.17 (4.11 to 99999)
    2.07 (1.87 to 2.30)
    1.28 (0.99 to 99999)
    No statistical analyses for this end point

    Secondary: Fold Change from Baseline in TAK-981-/Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Peripheral Blood Lymphocytes

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    End point title
    		 Fold Change from Baseline in TAK-981-/Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Peripheral Blood Lymphocytes
    End point description
    The level of TAK-981-SUMO adduct formation was evaluated by flow cytometry as the percentage of adduct formed in peripheral blood lymphocytes. Positive change denotes improvement. Pharmacodynamic Analysis Set included participants who provided evaluable blood samples (Cycle 1, Day 1 predose sample and at least 1 postdose sample). Subjects analysed is the number of participants with data available for analysis. 'n' denotes the number of participants available for analysis during the specified time-point.
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 1 (1 hour, 4 hours, 8 hours) and Day 8 (Pre-dose, 1 hour, 4 hours and 8 hours) (Cycle length = 21 days)
    End point values
    		 Dose Escalation: TAK-981 40 mg + Pembrolizumab Dose Escalation: TAK-981 60 mg + Pembrolizumab Dose Escalation: TAK-981 90 mg + Pembrolizumab Dose Escalation: TAK-981 120 mg + Pembrolizumab
    Number of subjects analysed
    3
    6
    18
    13
    Units: ratio
    arithmetic mean (standard deviation)
        Cycle 1 Day 1: ​1 Hour Post Dose(n=3,6,18,13)
    8.1 ( 1.06 )
    7.0 ( 3.12 )
    8.5 ( 3.38 )
    8.4 ( 2.40 )
        Cycle 1 Day 1: 4 Hours Post Dose(n=3,6,18,13)
    5.1 ( 0.82 )
    5.0 ( 1.90 )
    6.0 ( 1.80 )
    6.3 ( 1.70 )
        Cycle 1 Day 1: 6-8 Hours Post Dose(n=3,6,18,13)
    4.6 ( 0.61 )
    4.5 ( 1.87 )
    5.3 ( 1.58 )
    5.5 ( 1.29 )
        Cycle 1 Day 8: Predose(n=3,6,16,12)
    3.5 ( 0.53 )
    2.6 ( 0.96 )
    2.7 ( 1.43 )
    2.0 ( 0.68 )
        Cycle 1 Day 8: 1 Hour Post Dose(n=3,6,16,10)
    11.9 ( 3.52 )
    7.7 ( 2.88 )
    9.2 ( 4.68 )
    8.7 ( 2.01 )
        Cycle 1 Day 8: 4 Hours Post Dose(n=3,6,14,11)
    7.5 ( 1.52 )
    6.0 ( 2.66 )
    6.4 ( 2.90 )
    6.1 ( 2.12 )
        Cycle 1 Day 8: 6-8 Hours Post Dose(n=3,6,14,11)
    6.5 ( 1.08 )
    5.1 ( 2.30 )
    5.7 ( 2.64 )
    5.6 ( 1.96 )
    No statistical analyses for this end point

    Secondary: Fold Change from Baseline in SUMO 2/3 Inhibition in Peripheral Blood Lymphocytes

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    End point title
    		 Fold Change from Baseline in SUMO 2/3 Inhibition in Peripheral Blood Lymphocytes
    End point description
    SUMO pathway inhibition in blood was evaluated by flow cytometry in peripheral blood lymphocytes with an antibody recognizing SUMO 2/3 chains. Pharmacodynamic Analysis Set included participants who provided evaluable blood samples (Cycle 1, Day 1 predose sample and at least 1 postdose sample). Subjects analysed is the number of participants with data available for analysis. 'n' denotes the number of participants available for analysis during the specified time-point.
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 1 (1 hour, 4 hours, 8 hours) and Day 8 (Pre-dose, 1 hour, 4 hours and 8 hours) (Cycle length = 21 days)
    End point values
    		 Dose Escalation: TAK-981 40 mg + Pembrolizumab Dose Escalation: TAK-981 60 mg + Pembrolizumab Dose Escalation: TAK-981 90 mg + Pembrolizumab Dose Escalation: TAK-981 120 mg + Pembrolizumab
    Number of subjects analysed
    3
    6
    18
    13
    Units: ratio
    arithmetic mean (standard deviation)
        Cycle 1 Day 1: 1 Hour Post Dose(n=3,6,18,13)
    0.7 ( 0.14 )
    0.6 ( 0.21 )
    0.6 ( 0.18 )
    0.5 ( 0.08 )
        Cycle 1 Day 1: 4 Hours Post Dose(n=3,6,18,13)
    0.8 ( 0.07 )
    0.6 ( 0.12 )
    0.9 ( 0.54 )
    0.6 ( 0.11 )
        Cycle 1 Day 1: 6-8 Hours Post Dose(n=3,6,18,13)
    0.8 ( 0.08 )
    0.7 ( 0.19 )
    1.0 ( 0.68 )
    0.7 ( 0.34 )
        Cycle 1 Day 8: Predose(n=3,6,16,12)
    0.9 ( 0.24 )
    1.0 ( 0.35 )
    0.9 ( 0.36 )
    0.7 ( 0.39 )
        Cycle 1 Day 8: 1 Hour Post Dose(n=3,6,16,10)
    0.6 ( 0.14 )
    0.6 ( 0.23 )
    0.7 ( 0.34 )
    0.4 ( 0.15 )
        Cycle 1 Day 8: 4 Hours Post Dose(n=3,6,14,11)
    0.7 ( 0.22 )
    0.6 ( 0.15 )
    0.8 ( 0.58 )
    0.5 ( 0.17 )
        Cycle 1 Day 8: 6-8 Hours Post Dose(n=3,6,14,11)
    0.7 ( 0.29 )
    0.6 ( 0.11 )
    0.9 ( 0.53 )
    0.6 ( 0.22 )
    No statistical analyses for this end point

    Secondary: Phase 2: Percentage of Participants With One or More Treatment Emergent Adverse Events (TEAEs)

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    End point title
    		 Phase 2: Percentage of Participants With One or More Treatment Emergent Adverse Events (TEAEs)
    End point description
    An AE is any untoward medical occurrence in a participant administered a medicinal investigational drug. The untoward medical occurrence does not necessarily have to have a causal relationship with treatment. A TEAE is defined as an AE that occurs after administration of first dose of study drug and through 30 days after last dose of study drug or until start of subsequent antineoplastic therapy. AEs were evaluated according to NCI CTCAE, Version 5.0 except CRS, which was graded according to ASTCT Consensus Grading for CRS. Safety Analysis Set included participants who received at least 1 dose, even if incomplete, of study drug.
    End point type
    Secondary
    End point timeframe
    Up to approximately 25 months
    End point values
    		 Dose Expansion: Cohort A: Non-squamous NSCLC TAK-981 90 mg Dose Expansion: Cohort A: Non-squamous NSCLC TAK-981 120 mg Dose Expansion: Cohort B: Cervical Cancer Dose Expansion: Cohort C: MSS-CRC Dose Expansion: Cohort D: Cutaneous Melanoma Dose Expansion: Cohort E: Squamous NSCLC Dose Expansion: Cohort F: CPI Refractory Squamous or NSCLC
    Number of subjects analysed
    14
    9
    21
    9
    28
    15
    4
    Units: percentage of participants
        number (not applicable)
    100
    100
    100
    100
    100
    93.3
    100
    No statistical analyses for this end point

    Secondary: Phase 2: Number of Participants with One or More TEAEs Leading to Dose Modifications and Treatment Discontinuation

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    End point title
    		 Phase 2: Number of Participants with One or More TEAEs Leading to Dose Modifications and Treatment Discontinuation
    End point description
    An AE is any untoward medical occurrence in a participant administered a medicinal investigational drug. The untoward medical occurrence does not necessarily have to have a causal relationship with treatment. A TEAE is defined as an AE that occurs after administration of first dose of study drug and through 30 days after last dose of study drug or until start of subsequent antineoplastic therapy. Pembrolizumab is denoted as Pem. Safety Analysis Set included participants who received at least 1 dose, even if incomplete, of study drug.
    End point type
    Secondary
    End point timeframe
    Up to approximately 25 months
    End point values
    		 Dose Expansion: Cohort A: Non-squamous NSCLC TAK-981 90 mg Dose Expansion: Cohort A: Non-squamous NSCLC TAK-981 120 mg Dose Expansion: Cohort B: Cervical Cancer Dose Expansion: Cohort C: MSS-CRC Dose Expansion: Cohort D: Cutaneous Melanoma Dose Expansion: Cohort E: Squamous NSCLC Dose Expansion: Cohort F: CPI Refractory Squamous or NSCLC
    Number of subjects analysed
    14
    9
    21
    9
    28
    15
    4
    Units: participants
        TEAE Resulting in Dose Modifications of TAK-981
    11
    6
    15
    5
    15
    6
    4
        TEAE Resulting in Dose Modifications of Pem
    7
    5
    12
    4
    13
    2
    4
        TEAE Resulting in Drug Discontinuation of TAK-981
    1
    1
    6
    0
    6
    1
    0
        TEAE Resulting in Drug Discontinuation of Pem
    1
    3
    4
    0
    3
    1
    0
    No statistical analyses for this end point

    Secondary: Phase 2: Number of Participants With Grade 3 or Higher Treatment Emergent Adverse Events (TEAEs)

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    End point title
    		 Phase 2: Number of Participants With Grade 3 or Higher Treatment Emergent Adverse Events (TEAEs)
    End point description
    An AE means any untoward medical occurrence in a participant administered a pharmaceutical product. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product whether or not it is related to the medicinal product. A TEAE was defined as an adverse event which occurred on or after the first dose of study drug and no more than 30 days after the last dose of study drug. A severity grade was evaluated as per the NCI CTCAE Version 5.0, except for CRS, which was assessed by ASTCT Consensus Grading for CRS. Safety Analysis Set included participants who received at least 1 dose, even if incomplete, of study drug.
    End point type
    Secondary
    End point timeframe
    Up to approximately 25 months
    End point values
    		 Dose Expansion: Cohort A: Non-squamous NSCLC TAK-981 90 mg Dose Expansion: Cohort A: Non-squamous NSCLC TAK-981 120 mg Dose Expansion: Cohort B: Cervical Cancer Dose Expansion: Cohort C: MSS-CRC Dose Expansion: Cohort D: Cutaneous Melanoma Dose Expansion: Cohort E: Squamous NSCLC Dose Expansion: Cohort F: CPI Refractory Squamous or NSCLC
    Number of subjects analysed
    14
    9
    21
    9
    28
    15
    4
    Units: participants
    7
    5
    18
    8
    14
    4
    2
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Phase 1: Up to approximately 24 months, Phase 2: Up to approximately 25 months
    Adverse event reporting additional description
    Safety Analysis Set included participants who received at least 1 dose, even if incomplete, of study drug.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    27.0
    Reporting groups
    Reporting group title
    Dose Escalation: TAK-981 40 mg + Pembrolizumab
    Reporting group description
    		 Participants received TAK-981 40 mg, IV infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle and pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle until the RP2D was determined (for a maximum of 24 months).

    Reporting group title
    Dose Expansion: Cohort A: Non-squamous NSCLC TAK-981 120 mg
    Reporting group description
    		 Participants with non-squamous NSCLC received TAK-981 as IV infusion on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle up to disease progression or 24-months and pembrolizumab 200 mg IV infusion as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months.

    Reporting group title
    Dose Expansion: Cohort B: Cervical Cancer
    Reporting group description
    		 Participants with cervical cancer received TAK-981 as IV infusion on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle up to disease progression or 24-months and pembrolizumab 200 mg IV infusion as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months.

    Reporting group title
    Dose Expansion: Cohort A: Non-squamous NSCLC TAK-981 90 mg
    Reporting group description
    		 Participants with non-squamous NSCLC received TAK-981 as IV infusion on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle up to disease progression or 24-months and pembrolizumab 200 mg IV infusion as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months.

    Reporting group title
    Dose Expansion: Cohort D: Cutaneous Melanoma
    Reporting group description
    		 Participants with cutaneous melanoma received TAK-981 as IV infusion on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle up to disease progression or 24-months and pembrolizumab 200 mg IV infusion as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months.

    Reporting group title
    Dose Expansion: Cohort F: CPI Refractory Squamous/NSCLC
    Reporting group description
    		 Participants with CPI refractory squamous or non-squamous NSCLC received TAK-981 as IV infusion on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle up to disease progression or 24-months and pembrolizumab 200 mg IV infusion as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months.

    Reporting group title
    Dose Expansion: Cohort E: Squamous NSCLC
    Reporting group description
    		 Participants with squamous NSCLC received TAK-981 as IV infusion on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle up to disease progression or 24-months and pembrolizumab 200 mg IV infusion as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months.

    Reporting group title
    Dose Expansion: Cohort C: MSS-CRC
    Reporting group description
    		 Participants with MSS-CRC received TAK-981 as IV infusion on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle up to disease progression or 24-months and pembrolizumab 200 mg IV infusion as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months.

    Reporting group title
    Dose Escalation: TAK-981 120 mg + Pembrolizumab
    Reporting group description
    		 Participants received TAK-981, 120 mg, IV infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle and pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle until the RP2D was determined (for a maximum of 24 months).

    Reporting group title
    Dose Escalation: TAK-981 90 mg + Pembrolizumab
    Reporting group description
    		 Participants received TAK-981 90 mg, IV infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle and pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle until the RP2D was determined (for a maximum of 24 months).

    Reporting group title
    Dose Escalation: TAK-981 60 mg + Pembrolizumab
    Reporting group description
    		 Participants received TAK-981 60 mg, IV infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle and pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle until the RP2D was determined (for a maximum of 24 months).

    Serious adverse events
    		 Dose Escalation: TAK-981 40 mg + Pembrolizumab Dose Expansion: Cohort A: Non-squamous NSCLC TAK-981 120 mg Dose Expansion: Cohort B: Cervical Cancer Dose Expansion: Cohort A: Non-squamous NSCLC TAK-981 90 mg Dose Expansion: Cohort D: Cutaneous Melanoma Dose Expansion: Cohort F: CPI Refractory Squamous/NSCLC Dose Expansion: Cohort E: Squamous NSCLC Dose Expansion: Cohort C: MSS-CRC Dose Escalation: TAK-981 120 mg + Pembrolizumab Dose Escalation: TAK-981 90 mg + Pembrolizumab Dose Escalation: TAK-981 60 mg + Pembrolizumab
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 3 (0.00%)
    4 / 9 (44.44%)
    11 / 21 (52.38%)
    3 / 14 (21.43%)
    14 / 28 (50.00%)
    3 / 4 (75.00%)
    5 / 15 (33.33%)
    4 / 9 (44.44%)
    10 / 19 (52.63%)
    17 / 33 (51.52%)
    3 / 6 (50.00%)
         number of deaths (all causes)
    2
    4
    9
    2
    8
    1
    2
    2
    4
    8
    2
         number of deaths resulting from adverse events
    0
    0
    1
    0
    2
    0
    1
    1
    2
    4
    1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Acute myeloid leukaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    1 / 33 (3.03%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cancer pain
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 9 (11.11%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    1 / 33 (3.03%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cervix carcinoma
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    1 / 21 (4.76%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Colorectal cancer
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    1 / 6 (16.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Infected neoplasm
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    1 / 21 (4.76%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Malignant neoplasm progression
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    1 / 28 (3.57%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    1 / 9 (11.11%)
    1 / 19 (5.26%)
    1 / 33 (3.03%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 1
    0 / 0
    Metastases to central nervous system
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    1 / 33 (3.03%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Non-small cell lung cancer
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    1 / 33 (3.03%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Malignant melanoma
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    1 / 28 (3.57%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metastatic malignant melanoma
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    1 / 28 (3.57%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Aortic aneurysm rupture
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    1 / 19 (5.26%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Hypotension
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    1 / 28 (3.57%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    1 / 19 (5.26%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    1 / 28 (3.57%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Device related thrombosis
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 9 (11.11%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 9 (11.11%)
    1 / 21 (4.76%)
    0 / 14 (0.00%)
    1 / 28 (3.57%)
    0 / 4 (0.00%)
    1 / 15 (6.67%)
    1 / 9 (11.11%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
    0 / 1
    0 / 0
    1 / 1
    0 / 0
    1 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Malaise
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    1 / 33 (3.03%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Non-cardiac chest pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    1 / 28 (3.57%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oedema peripheral
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    1 / 21 (4.76%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Immune system disorders
    Anaphylactic shock
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    1 / 21 (4.76%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cytokine release syndrome
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    1 / 21 (4.76%)
    1 / 14 (7.14%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    1 / 19 (5.26%)
    3 / 33 (9.09%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    3 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    1 / 21 (4.76%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    1 / 33 (3.03%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Immune-mediated lung disease
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    1 / 21 (4.76%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    1 / 28 (3.57%)
    1 / 4 (25.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    1 / 33 (3.03%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pleuritic pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    1 / 21 (4.76%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    1 / 21 (4.76%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary oedema
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    1 / 28 (3.57%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Mental status changes
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    1 / 9 (11.11%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Platelet count decreased
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 9 (11.11%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    1 / 15 (6.67%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Tracheal obstruction
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    1 / 19 (5.26%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis radiation
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    1 / 21 (4.76%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infusion related reaction
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    1 / 28 (3.57%)
    0 / 4 (0.00%)
    1 / 15 (6.67%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    1 / 33 (3.03%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Post procedural complication
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    1 / 15 (6.67%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Transfusion-related acute lung injury
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    1 / 33 (3.03%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Traumatic haemothorax
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    1 / 21 (4.76%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Arrhythmia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    1 / 15 (6.67%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    2 / 28 (7.14%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrioventricular block
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    1 / 15 (6.67%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pericardial effusion
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    1 / 6 (16.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Supraventricular tachycardia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    1 / 15 (6.67%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Ischaemic stroke
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    1 / 28 (3.57%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spinal cord compression
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    1 / 28 (3.57%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Aplasia pure red cell
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    1 / 6 (16.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Anaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    2 / 21 (9.52%)
    0 / 14 (0.00%)
    2 / 28 (7.14%)
    1 / 4 (25.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    1 / 19 (5.26%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    2 / 2
    0 / 0
    0 / 2
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal distension
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    1 / 33 (3.03%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea haemorrhagic
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    1 / 33 (3.03%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ascites
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    1 / 19 (5.26%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Large intestinal obstruction
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    2 / 33 (6.06%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    1 / 6 (16.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    1 / 33 (3.03%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intestinal perforation
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    1 / 15 (6.67%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haematochezia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    1 / 19 (5.26%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Impaired gastric emptying
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    1 / 19 (5.26%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    1 / 9 (11.11%)
    0 / 19 (0.00%)
    1 / 33 (3.03%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Stomatitis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    1 / 15 (6.67%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    0 / 3 (0.00%)
    2 / 9 (22.22%)
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Biliary obstruction
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    2 / 19 (10.53%)
    1 / 33 (3.03%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholangitis acute
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    1 / 19 (5.26%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatic function abnormal
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    1 / 33 (3.03%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyperbilirubinaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    1 / 33 (3.03%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Jaundice cholestatic
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    1 / 19 (5.26%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Malignant biliary obstruction
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    1 / 19 (5.26%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Dermatomyositis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    1 / 33 (3.03%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Hydronephrosis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    1 / 21 (4.76%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Endocrine disorders
    Adrenal insufficiency
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    1 / 21 (4.76%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    1 / 33 (3.03%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Myalgia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    1 / 28 (3.57%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    2 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    1 / 28 (3.57%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    1 / 19 (5.26%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infection
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    1 / 4 (25.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Orchitis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    1 / 21 (4.76%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    2 / 21 (9.52%)
    1 / 14 (7.14%)
    1 / 28 (3.57%)
    1 / 4 (25.00%)
    1 / 15 (6.67%)
    1 / 9 (11.11%)
    0 / 19 (0.00%)
    2 / 33 (6.06%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 3
    0 / 1
    0 / 1
    0 / 1
    0 / 1
    0 / 1
    0 / 0
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    Pneumonia bacterial
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    2 / 28 (7.14%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 9 (11.11%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    1 / 9 (11.11%)
    0 / 19 (0.00%)
    2 / 33 (6.06%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Hypercalcaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    1 / 21 (4.76%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypokalaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    1 / 28 (3.57%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Dose Escalation: TAK-981 40 mg + Pembrolizumab Dose Expansion: Cohort A: Non-squamous NSCLC TAK-981 120 mg Dose Expansion: Cohort B: Cervical Cancer Dose Expansion: Cohort A: Non-squamous NSCLC TAK-981 90 mg Dose Expansion: Cohort D: Cutaneous Melanoma Dose Expansion: Cohort F: CPI Refractory Squamous/NSCLC Dose Expansion: Cohort E: Squamous NSCLC Dose Expansion: Cohort C: MSS-CRC Dose Escalation: TAK-981 120 mg + Pembrolizumab Dose Escalation: TAK-981 90 mg + Pembrolizumab Dose Escalation: TAK-981 60 mg + Pembrolizumab
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    3 / 3 (100.00%)
    9 / 9 (100.00%)
    21 / 21 (100.00%)
    14 / 14 (100.00%)
    28 / 28 (100.00%)
    4 / 4 (100.00%)
    14 / 15 (93.33%)
    9 / 9 (100.00%)
    19 / 19 (100.00%)
    33 / 33 (100.00%)
    6 / 6 (100.00%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Nervous system neoplasm
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    1 / 9 (11.11%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    Tumour associated fever
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    1 / 19 (5.26%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    2
    0
    0
    Tumour pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    1 / 21 (4.76%)
    0 / 14 (0.00%)
    1 / 28 (3.57%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    1 / 9 (11.11%)
    1 / 19 (5.26%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    1
    0
    0
    1
    1
    0
    0
    Cancer pain
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 9 (11.11%)
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    0 / 28 (0.00%)
    1 / 4 (25.00%)
    0 / 15 (0.00%)
    2 / 9 (22.22%)
    1 / 19 (5.26%)
    0 / 33 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    1
    0
    1
    0
    1
    0
    3
    1
    0
    1
    Colon cancer
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    1 / 19 (5.26%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Vascular disorders
    Hypotension
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    1 / 21 (4.76%)
    1 / 14 (7.14%)
    2 / 28 (7.14%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    1 / 9 (11.11%)
    2 / 19 (10.53%)
    3 / 33 (9.09%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    7
    2
    0
    0
    3
    3
    3
    0
    Poor peripheral circulation
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    1 / 19 (5.26%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    2
    0
    0
    Hot flush
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    1 / 19 (5.26%)
    1 / 33 (3.03%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    1
    0
    Hypertension
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    3 / 28 (10.71%)
    0 / 4 (0.00%)
    1 / 15 (6.67%)
    0 / 9 (0.00%)
    1 / 19 (5.26%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    4
    0
    1
    0
    1
    0
    0
    Vasculitis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    2 / 33 (6.06%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    3
    0
    General disorders and administration site conditions
    Early satiety
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    1 / 9 (11.11%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    Asthenia
         subjects affected / exposed
    0 / 3 (0.00%)
    3 / 9 (33.33%)
    4 / 21 (19.05%)
    0 / 14 (0.00%)
    1 / 28 (3.57%)
    1 / 4 (25.00%)
    3 / 15 (20.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    2 / 33 (6.06%)
    0 / 6 (0.00%)
         occurrences all number
    0
    3
    5
    0
    2
    2
    3
    0
    0
    3
    0
    Chills
         subjects affected / exposed
    0 / 3 (0.00%)
    2 / 9 (22.22%)
    1 / 21 (4.76%)
    5 / 14 (35.71%)
    4 / 28 (14.29%)
    1 / 4 (25.00%)
    1 / 15 (6.67%)
    1 / 9 (11.11%)
    11 / 19 (57.89%)
    12 / 33 (36.36%)
    1 / 6 (16.67%)
         occurrences all number
    0
    2
    1
    8
    6
    1
    1
    1
    20
    27
    1
    Fatigue
         subjects affected / exposed
    2 / 3 (66.67%)
    5 / 9 (55.56%)
    6 / 21 (28.57%)
    5 / 14 (35.71%)
    9 / 28 (32.14%)
    1 / 4 (25.00%)
    0 / 15 (0.00%)
    5 / 9 (55.56%)
    4 / 19 (21.05%)
    13 / 33 (39.39%)
    1 / 6 (16.67%)
         occurrences all number
    3
    8
    6
    9
    12
    1
    0
    8
    9
    15
    1
    Feeling cold
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Injection site pain
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 9 (11.11%)
    2 / 21 (9.52%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    3
    0
    0
    0
    0
    0
    0
    0
    0
    Peripheral swelling
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    1 / 4 (25.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Pyrexia
         subjects affected / exposed
    0 / 3 (0.00%)
    4 / 9 (44.44%)
    11 / 21 (52.38%)
    9 / 14 (64.29%)
    11 / 28 (39.29%)
    1 / 4 (25.00%)
    6 / 15 (40.00%)
    3 / 9 (33.33%)
    14 / 19 (73.68%)
    17 / 33 (51.52%)
    1 / 6 (16.67%)
         occurrences all number
    0
    19
    40
    21
    80
    1
    22
    4
    59
    37
    5
    General physical health deterioration
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Influenza like illness
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    2 / 28 (7.14%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    3 / 19 (15.79%)
    1 / 33 (3.03%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    0
    0
    5
    1
    0
    Infusion site extravasation
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    1 / 28 (3.57%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    1 / 19 (5.26%)
    0 / 33 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    1
    0
    1
    Injection site erythema
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    2 / 21 (9.52%)
    1 / 14 (7.14%)
    1 / 28 (3.57%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    3
    1
    1
    0
    0
    0
    0
    0
    0
    Non-cardiac chest pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    1 / 21 (4.76%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    1 / 4 (25.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    1
    0
    0
    1
    0
    0
    0
    0
    1
    Oedema peripheral
         subjects affected / exposed
    0 / 3 (0.00%)
    2 / 9 (22.22%)
    2 / 21 (9.52%)
    2 / 14 (14.29%)
    5 / 28 (17.86%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    3 / 19 (15.79%)
    2 / 33 (6.06%)
    0 / 6 (0.00%)
         occurrences all number
    0
    2
    3
    5
    5
    0
    0
    0
    5
    2
    0
    Pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    1 / 28 (3.57%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    1 / 33 (3.03%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    1
    0
    0
    0
    0
    1
    0
    Malaise
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    2 / 21 (9.52%)
    1 / 14 (7.14%)
    1 / 28 (3.57%)
    0 / 4 (0.00%)
    1 / 15 (6.67%)
    1 / 9 (11.11%)
    0 / 19 (0.00%)
    4 / 33 (12.12%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    2
    1
    1
    0
    1
    1
    0
    7
    0
    Swelling face
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    1 / 19 (5.26%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    2
    0
    0
    Localised oedema
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    1 / 19 (5.26%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Immune system disorders
    Cytokine release syndrome
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    1 / 21 (4.76%)
    1 / 14 (7.14%)
    1 / 28 (3.57%)
    0 / 4 (0.00%)
    1 / 15 (6.67%)
    0 / 9 (0.00%)
    1 / 19 (5.26%)
    3 / 33 (9.09%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    2
    1
    3
    0
    1
    0
    8
    4
    0
    Reproductive system and breast disorders
    Epididymal cyst
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Penile oedema
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    1 / 19 (5.26%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Perineal pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    1 / 19 (5.26%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    3 / 21 (14.29%)
    2 / 14 (14.29%)
    10 / 28 (35.71%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    2 / 9 (22.22%)
    4 / 19 (21.05%)
    3 / 33 (9.09%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    3
    2
    11
    0
    0
    2
    4
    3
    0
    Dyspnoea exertional
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    1 / 19 (5.26%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    2
    0
    0
    Epistaxis
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 9 (11.11%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    1 / 28 (3.57%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    1 / 19 (5.26%)
    1 / 33 (3.03%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    1
    0
    0
    0
    1
    1
    0
    Haemoptysis
         subjects affected / exposed
    0 / 3 (0.00%)
    2 / 9 (22.22%)
    1 / 21 (4.76%)
    1 / 14 (7.14%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    1 / 15 (6.67%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    2
    1
    1
    0
    0
    1
    0
    0
    0
    0
    Dysphonia
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 9 (11.11%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    1 / 33 (3.03%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Dyspnoea
         subjects affected / exposed
    1 / 3 (33.33%)
    1 / 9 (11.11%)
    2 / 21 (9.52%)
    2 / 14 (14.29%)
    1 / 28 (3.57%)
    2 / 4 (50.00%)
    0 / 15 (0.00%)
    1 / 9 (11.11%)
    4 / 19 (21.05%)
    5 / 33 (15.15%)
    0 / 6 (0.00%)
         occurrences all number
    1
    2
    2
    2
    1
    2
    0
    1
    6
    5
    0
    Oropharyngeal pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    1 / 28 (3.57%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    1 / 19 (5.26%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    0
    0
    1
    0
    0
    Rhinorrhoea
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    1 / 28 (3.57%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    1 / 9 (11.11%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    1
    0
    0
    0
    Productive cough
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    1 / 21 (4.76%)
    1 / 14 (7.14%)
    2 / 28 (7.14%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    1
    2
    0
    0
    0
    0
    0
    0
    Pleural effusion
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    1 / 4 (25.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Psychiatric disorders
    Agitation
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Anxiety
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    1 / 21 (4.76%)
    0 / 14 (0.00%)
    2 / 28 (7.14%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    1 / 9 (11.11%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    2
    0
    0
    1
    0
    0
    0
    Depression
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    2 / 28 (7.14%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    1 / 9 (11.11%)
    0 / 19 (0.00%)
    1 / 33 (3.03%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    0
    1
    0
    1
    0
    Hallucination
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    1 / 9 (11.11%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    Insomnia
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 9 (11.11%)
    2 / 21 (9.52%)
    1 / 14 (7.14%)
    1 / 28 (3.57%)
    0 / 4 (0.00%)
    1 / 15 (6.67%)
    1 / 9 (11.11%)
    0 / 19 (0.00%)
    2 / 33 (6.06%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    2
    1
    1
    0
    1
    1
    0
    2
    0
    Libido decreased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Investigations
    Blood alkaline phosphatase increased
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 9 (11.11%)
    4 / 21 (19.05%)
    2 / 14 (14.29%)
    1 / 28 (3.57%)
    0 / 4 (0.00%)
    1 / 15 (6.67%)
    1 / 9 (11.11%)
    0 / 19 (0.00%)
    5 / 33 (15.15%)
    0 / 6 (0.00%)
         occurrences all number
    0
    2
    10
    3
    1
    0
    1
    1
    0
    5
    0
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 3 (0.00%)
    4 / 9 (44.44%)
    4 / 21 (19.05%)
    4 / 14 (28.57%)
    3 / 28 (10.71%)
    0 / 4 (0.00%)
    1 / 15 (6.67%)
    2 / 9 (22.22%)
    2 / 19 (10.53%)
    13 / 33 (39.39%)
    0 / 6 (0.00%)
         occurrences all number
    0
    6
    11
    9
    3
    0
    2
    3
    2
    17
    0
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 3 (0.00%)
    2 / 9 (22.22%)
    4 / 21 (19.05%)
    4 / 14 (28.57%)
    2 / 28 (7.14%)
    0 / 4 (0.00%)
    1 / 15 (6.67%)
    0 / 9 (0.00%)
    1 / 19 (5.26%)
    7 / 33 (21.21%)
    0 / 6 (0.00%)
         occurrences all number
    0
    5
    9
    5
    3
    0
    1
    0
    1
    8
    0
    Blood bilirubin increased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    1 / 21 (4.76%)
    0 / 14 (0.00%)
    2 / 28 (7.14%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    3
    0
    0
    0
    0
    0
    0
    Blood creatinine increased
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 9 (11.11%)
    1 / 21 (4.76%)
    1 / 14 (7.14%)
    1 / 28 (3.57%)
    1 / 4 (25.00%)
    1 / 15 (6.67%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    3 / 33 (9.09%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    1
    1
    1
    2
    1
    0
    0
    7
    0
    Blood thyroid stimulating hormone increased
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 9 (11.11%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    CD4 lymphocytes decreased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    3 / 21 (14.29%)
    0 / 14 (0.00%)
    2 / 28 (7.14%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    3
    0
    4
    0
    0
    0
    0
    0
    0
    Blood lactate dehydrogenase increased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    5 / 28 (17.86%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    1 / 33 (3.03%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    8
    0
    0
    0
    0
    2
    0
    Brain natriuretic peptide increased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    C-reactive protein increased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    1 / 28 (3.57%)
    2 / 4 (50.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    3
    0
    0
    0
    0
    0
    Blood pressure increased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    1 / 15 (6.67%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Ejection fraction decreased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Electrocardiogram QT prolonged
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 9 (11.11%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    1 / 28 (3.57%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    1 / 19 (5.26%)
    1 / 33 (3.03%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    2
    0
    0
    0
    1
    1
    0
    Electrocardiogram ST-T segment abnormal
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 9 (11.11%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 9 (11.11%)
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    1 / 15 (6.67%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    1 / 33 (3.03%)
    0 / 6 (0.00%)
         occurrences all number
    0
    2
    0
    2
    0
    0
    2
    0
    0
    1
    0
    Interleukin level increased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    1 / 15 (6.67%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Lipase increased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Lymphocyte count decreased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    4 / 21 (19.05%)
    1 / 14 (7.14%)
    3 / 28 (10.71%)
    0 / 4 (0.00%)
    2 / 15 (13.33%)
    0 / 9 (0.00%)
    1 / 19 (5.26%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    10
    7
    5
    0
    9
    0
    1
    0
    0
    SARS-CoV-2 test positive
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    2 / 28 (7.14%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    1 / 9 (11.11%)
    0 / 19 (0.00%)
    2 / 33 (6.06%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    0
    1
    0
    2
    0
    Procalcitonin increased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    1 / 15 (6.67%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Platelet count decreased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    2 / 28 (7.14%)
    0 / 4 (0.00%)
    1 / 15 (6.67%)
    0 / 9 (0.00%)
    3 / 19 (15.79%)
    6 / 33 (18.18%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    4
    3
    0
    1
    0
    7
    14
    0
    Neutrophil count decreased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    2 / 21 (9.52%)
    0 / 14 (0.00%)
    1 / 28 (3.57%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    2 / 33 (6.06%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    5
    0
    1
    0
    0
    0
    0
    5
    0
    N-terminal prohormone brain natriuretic peptide increased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    T-lymphocyte count decreased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    2 / 21 (9.52%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    6
    0
    0
    0
    0
    0
    0
    0
    0
    Weight decreased
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 9 (11.11%)
    2 / 21 (9.52%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    1 / 9 (11.11%)
    2 / 19 (10.53%)
    2 / 33 (6.06%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    2
    0
    0
    0
    0
    2
    4
    2
    0
    White blood cell count decreased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    3 / 21 (14.29%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    2 / 33 (6.06%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    7
    0
    0
    0
    0
    0
    0
    4
    0
    Injury, poisoning and procedural complications
    Limb injury
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    1 / 15 (6.67%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Infusion related reaction
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    1 / 21 (4.76%)
    0 / 14 (0.00%)
    1 / 28 (3.57%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    2 / 19 (10.53%)
    7 / 33 (21.21%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    13
    0
    1
    0
    0
    0
    4
    19
    0
    Oral contusion
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    1 / 28 (3.57%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    1 / 19 (5.26%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    2
    0
    0
    Fall
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    1 / 28 (3.57%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    1 / 33 (3.03%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    1
    0
    0
    0
    0
    1
    0
    Cardiac disorders
    Angina pectoris
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    1 / 19 (5.26%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    2
    0
    0
    Sinus tachycardia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    1 / 21 (4.76%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    1 / 15 (6.67%)
    0 / 9 (0.00%)
    2 / 19 (10.53%)
    1 / 33 (3.03%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    1
    0
    2
    1
    0
    Supraventricular tachycardia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    1 / 19 (5.26%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Atrial fibrillation
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    1 / 28 (3.57%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    4
    1
    0
    0
    0
    0
    0
    0
    Atrial flutter
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    1 / 4 (25.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Cardiac failure
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    2 / 28 (7.14%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    2
    0
    0
    0
    0
    0
    0
    Palpitations
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    1 / 21 (4.76%)
    0 / 14 (0.00%)
    1 / 28 (3.57%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    1 / 9 (11.11%)
    1 / 19 (5.26%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    1
    0
    0
    1
    2
    0
    0
    Pericardial effusion
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 9 (11.11%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Paroxysmal arrhythmia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Nervous system disorders
    Balance disorder
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Cerebrovascular accident
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Depressed level of consciousness
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    1 / 9 (11.11%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    Dizziness
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    1 / 33 (3.03%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    0
    0
    0
    0
    1
    0
    Dysgeusia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    1 / 28 (3.57%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    2 / 9 (22.22%)
    1 / 19 (5.26%)
    1 / 33 (3.03%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    2
    1
    1
    0
    Headache
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    2 / 21 (9.52%)
    3 / 14 (21.43%)
    5 / 28 (17.86%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    2 / 9 (22.22%)
    4 / 19 (21.05%)
    6 / 33 (18.18%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    2
    3
    12
    0
    0
    4
    4
    7
    1
    Hypoaesthesia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    1 / 21 (4.76%)
    1 / 14 (7.14%)
    1 / 28 (3.57%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    2
    2
    1
    0
    0
    0
    0
    0
    0
    Paraesthesia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    2 / 14 (14.29%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    1 / 9 (11.11%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    0
    0
    1
    0
    0
    0
    Burning sensation
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    2
    Restless legs syndrome
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    1 / 19 (5.26%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Seizure
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    1 / 15 (6.67%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Somnolence
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 9 (11.11%)
    1 / 21 (4.76%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    2
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Tremor
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    1 / 9 (11.11%)
    1 / 19 (5.26%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    0
    0
    1
    1
    0
    0
    Parosmia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    1 / 9 (11.11%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    Polyneuropathy
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 9 (11.11%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    2 / 9 (22.22%)
    13 / 21 (61.90%)
    3 / 14 (21.43%)
    7 / 28 (25.00%)
    2 / 4 (50.00%)
    2 / 15 (13.33%)
    3 / 9 (33.33%)
    6 / 19 (31.58%)
    16 / 33 (48.48%)
    1 / 6 (16.67%)
         occurrences all number
    0
    5
    24
    5
    9
    7
    2
    8
    7
    32
    3
    Anaemia of chronic disease
         subjects affected / exposed
    0 / 3 (0.00%)
    2 / 9 (22.22%)
    1 / 21 (4.76%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    2
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Anaemia of malignant disease
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    1 / 21 (4.76%)
    0 / 14 (0.00%)
    1 / 28 (3.57%)
    0 / 4 (0.00%)
    1 / 15 (6.67%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    2
    0
    2
    0
    0
    0
    0
    Neutropenia
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 9 (11.11%)
    2 / 21 (9.52%)
    4 / 14 (28.57%)
    2 / 28 (7.14%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    1 / 33 (3.03%)
    0 / 6 (0.00%)
         occurrences all number
    0
    10
    12
    8
    3
    0
    0
    0
    0
    1
    0
    Thrombocytopenia
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 9 (11.11%)
    1 / 21 (4.76%)
    2 / 14 (14.29%)
    2 / 28 (7.14%)
    1 / 4 (25.00%)
    1 / 15 (6.67%)
    1 / 9 (11.11%)
    4 / 19 (21.05%)
    1 / 33 (3.03%)
    0 / 6 (0.00%)
         occurrences all number
    0
    4
    4
    8
    4
    1
    1
    1
    18
    1
    0
    Lymphopenia
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 9 (11.11%)
    1 / 21 (4.76%)
    0 / 14 (0.00%)
    1 / 28 (3.57%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    2
    0
    1
    0
    0
    0
    0
    0
    0
    Leukocytosis
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 9 (11.11%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    1 / 4 (25.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Leukopenia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    2 / 21 (9.52%)
    0 / 14 (0.00%)
    1 / 28 (3.57%)
    0 / 4 (0.00%)
    1 / 15 (6.67%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    6
    0
    2
    0
    1
    0
    0
    0
    0
    Lymph node pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    1 / 15 (6.67%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Ear and labyrinth disorders
    Cerumen impaction
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    1 / 19 (5.26%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Vertigo
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    1 / 15 (6.67%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Tinnitus
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    1 / 19 (5.26%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Eye disorders
    Dry eye
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 9 (11.11%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Diplopia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    1 / 19 (5.26%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Visual acuity reduced
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    1 / 21 (4.76%)
    1 / 14 (7.14%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    0
    0
    0
    0
    0
    0
    Ocular hyperaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Gastrointestinal disorders
    Abdominal pain upper
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 9 (11.11%)
    5 / 21 (23.81%)
    1 / 14 (7.14%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    2 / 33 (6.06%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    5
    1
    0
    0
    0
    0
    0
    2
    0
    Abdominal pain lower
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    1 / 19 (5.26%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Abdominal pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    1 / 28 (3.57%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    3 / 9 (33.33%)
    1 / 19 (5.26%)
    3 / 33 (9.09%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    4
    1
    3
    0
    Abdominal distension
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    2 / 9 (22.22%)
    0 / 19 (0.00%)
    1 / 33 (3.03%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    2
    0
    1
    0
    Anal fissure
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    1 / 28 (3.57%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    1 / 9 (11.11%)
    0 / 19 (0.00%)
    1 / 33 (3.03%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    1
    0
    1
    0
    Angular cheilitis
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 9 (11.11%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    1 / 28 (3.57%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Diarrhoea
         subjects affected / exposed
    1 / 3 (33.33%)
    2 / 9 (22.22%)
    7 / 21 (33.33%)
    3 / 14 (21.43%)
    7 / 28 (25.00%)
    1 / 4 (25.00%)
    3 / 15 (20.00%)
    3 / 9 (33.33%)
    9 / 19 (47.37%)
    9 / 33 (27.27%)
    0 / 6 (0.00%)
         occurrences all number
    1
    4
    8
    3
    17
    1
    5
    4
    12
    16
    0
    Defaecation urgency
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    1 / 19 (5.26%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Constipation
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    3 / 21 (14.29%)
    0 / 14 (0.00%)
    1 / 28 (3.57%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    1 / 9 (11.11%)
    1 / 19 (5.26%)
    3 / 33 (9.09%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    4
    0
    1
    0
    0
    1
    1
    3
    1
    Cheilitis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Ascites
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    1 / 19 (5.26%)
    1 / 33 (3.03%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    1
    0
    Flatulence
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    1 / 19 (5.26%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Dyspepsia
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    1 / 9 (11.11%)
    1 / 19 (5.26%)
    1 / 33 (3.03%)
    1 / 6 (16.67%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    1
    1
    3
    1
    Dry mouth
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 9 (11.11%)
    2 / 21 (9.52%)
    3 / 14 (21.43%)
    1 / 28 (3.57%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    1 / 19 (5.26%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    2
    3
    1
    0
    0
    0
    1
    0
    0
    Dysphagia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    1 / 28 (3.57%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    1 / 9 (11.11%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    0
    1
    0
    0
    0
    Haemorrhoidal haemorrhage
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 9 (11.11%)
    1 / 21 (4.76%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    1 / 19 (5.26%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    0
    0
    1
    0
    0
    Large intestine polyp
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    1 / 19 (5.26%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Intestinal polyp
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    1 / 19 (5.26%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Immune-mediated enterocolitis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    1 / 19 (5.26%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Rectal haemorrhage
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    1 / 19 (5.26%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Odynophagia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    1 / 28 (3.57%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    1
    0
    0
    0
    0
    0
    0
    Nausea
         subjects affected / exposed
    1 / 3 (33.33%)
    6 / 9 (66.67%)
    9 / 21 (42.86%)
    3 / 14 (21.43%)
    13 / 28 (46.43%)
    1 / 4 (25.00%)
    1 / 15 (6.67%)
    2 / 9 (22.22%)
    5 / 19 (26.32%)
    8 / 33 (24.24%)
    0 / 6 (0.00%)
         occurrences all number
    1
    10
    14
    6
    40
    1
    1
    2
    5
    10
    0
    Mouth ulceration
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 9 (11.11%)
    1 / 21 (4.76%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Lip oedema
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    1 / 19 (5.26%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Haemorrhoids
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    2 / 19 (10.53%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    2
    0
    0
    Tongue ulceration
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    1 / 4 (25.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Vomiting
         subjects affected / exposed
    2 / 3 (66.67%)
    2 / 9 (22.22%)
    5 / 21 (23.81%)
    4 / 14 (28.57%)
    4 / 28 (14.29%)
    1 / 4 (25.00%)
    1 / 15 (6.67%)
    2 / 9 (22.22%)
    5 / 19 (26.32%)
    7 / 33 (21.21%)
    0 / 6 (0.00%)
         occurrences all number
    2
    2
    5
    5
    19
    6
    1
    2
    6
    7
    0
    Stomatitis
         subjects affected / exposed
    0 / 3 (0.00%)
    2 / 9 (22.22%)
    1 / 21 (4.76%)
    4 / 14 (28.57%)
    8 / 28 (28.57%)
    0 / 4 (0.00%)
    1 / 15 (6.67%)
    3 / 9 (33.33%)
    8 / 19 (42.11%)
    8 / 33 (24.24%)
    0 / 6 (0.00%)
         occurrences all number
    0
    2
    1
    4
    16
    0
    5
    4
    11
    13
    0
    Hepatobiliary disorders
    Biliary obstruction
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    1 / 19 (5.26%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Cholangitis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    1 / 19 (5.26%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Hyperbilirubinaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    1 / 19 (5.26%)
    1 / 33 (3.03%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    3
    1
    0
    Hypertransaminasaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    1 / 15 (6.67%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Skin and subcutaneous tissue disorders
    Angioedema
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    1 / 19 (5.26%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Dermatitis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    1 / 21 (4.76%)
    1 / 14 (7.14%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    1 / 15 (6.67%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    0
    1
    0
    0
    0
    0
    Dermatitis acneiform
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    1 / 21 (4.76%)
    0 / 14 (0.00%)
    4 / 28 (14.29%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    2 / 19 (10.53%)
    2 / 33 (6.06%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    4
    0
    7
    0
    0
    0
    2
    2
    0
    Alopecia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    1 / 21 (4.76%)
    1 / 14 (7.14%)
    1 / 28 (3.57%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    1 / 19 (5.26%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    1
    1
    0
    0
    0
    1
    0
    0
    Erythema
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    1 / 21 (4.76%)
    1 / 14 (7.14%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    1 / 19 (5.26%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    0
    0
    0
    1
    0
    0
    Dermatitis bullous
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    1 / 19 (5.26%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Dry skin
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    1 / 19 (5.26%)
    1 / 33 (3.03%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    1
    0
    Dermatitis psoriasiform
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    1 / 19 (5.26%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    2
    0
    0
    Hyperhidrosis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    2 / 33 (6.06%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    3
    0
    Ingrowing nail
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    1 / 19 (5.26%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Rash
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    1 / 9 (11.11%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    1
    0
    0
    0
    Perioral dermatitis
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 9 (11.11%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Palmar-plantar erythrodysaesthesia syndrome
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    1 / 19 (5.26%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Night sweats
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    2 / 28 (7.14%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    2 / 19 (10.53%)
    1 / 33 (3.03%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    0
    0
    2
    1
    0
    Psoriasis
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 9 (11.11%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    1 / 33 (3.03%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Skin ulcer
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    1 / 15 (6.67%)
    0 / 9 (0.00%)
    1 / 19 (5.26%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    1
    0
    0
    Rash erythematous
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    1 / 21 (4.76%)
    1 / 14 (7.14%)
    1 / 28 (3.57%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    1
    1
    0
    0
    0
    0
    0
    0
    Pruritus
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 9 (11.11%)
    2 / 21 (9.52%)
    1 / 14 (7.14%)
    6 / 28 (21.43%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    3 / 19 (15.79%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    2
    3
    1
    9
    0
    0
    0
    4
    0
    0
    Rash vesicular
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 9 (11.11%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Rash maculo-papular
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    3 / 21 (14.29%)
    1 / 14 (7.14%)
    3 / 28 (10.71%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    4 / 19 (21.05%)
    2 / 33 (6.06%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    9
    1
    6
    0
    0
    0
    6
    4
    0
    Rash macular
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Urticaria
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    1 / 19 (5.26%)
    0 / 33 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    2
    0
    1
    Vitiligo
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    7 / 28 (25.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    10
    0
    0
    0
    0
    0
    0
    Renal and urinary disorders
    Chromaturia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    1 / 19 (5.26%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Cystitis noninfective
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Leukocyturia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Proteinuria
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 9 (11.11%)
    2 / 21 (9.52%)
    1 / 14 (7.14%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    1 / 33 (3.03%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    2
    1
    0
    0
    0
    0
    0
    1
    0
    Haematuria
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    1 / 21 (4.76%)
    2 / 14 (14.29%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    1 / 33 (3.03%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    2
    0
    0
    0
    0
    0
    1
    0
    Dysuria
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    1 / 21 (4.76%)
    0 / 14 (0.00%)
    2 / 28 (7.14%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    1 / 19 (5.26%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    2
    0
    0
    0
    1
    0
    0
    Hydronephrosis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    1 / 9 (11.11%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    Renal impairment
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    1 / 21 (4.76%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    1 / 19 (5.26%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    1
    0
    0
    Urinary retention
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    1 / 28 (3.57%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    1 / 33 (3.03%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    1
    0
    0
    0
    0
    1
    0
    Urinary incontinence
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    1 / 33 (3.03%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    3
    0
    Endocrine disorders
    Hyperthyroidism
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 9 (11.11%)
    1 / 21 (4.76%)
    0 / 14 (0.00%)
    1 / 28 (3.57%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    1 / 19 (5.26%)
    1 / 33 (3.03%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    1
    0
    1
    0
    0
    0
    1
    1
    0
    Hypothyroidism
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    5 / 21 (23.81%)
    0 / 14 (0.00%)
    2 / 28 (7.14%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    1 / 19 (5.26%)
    2 / 33 (6.06%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    5
    0
    2
    0
    0
    0
    1
    2
    0
    Adrenal insufficiency
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    1 / 28 (3.57%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    1 / 9 (11.11%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    1
    0
    0
    1
    Musculoskeletal and connective tissue disorders
    Joint stiffness
         subjects affected / exposed
    0 / 3 (0.00%)
    2 / 9 (22.22%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Bone pain
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 9 (11.11%)
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    5
    0
    0
    0
    0
    0
    0
    0
    Arthralgia
         subjects affected / exposed
    2 / 3 (66.67%)
    1 / 9 (11.11%)
    4 / 21 (19.05%)
    4 / 14 (28.57%)
    5 / 28 (17.86%)
    0 / 4 (0.00%)
    1 / 15 (6.67%)
    2 / 9 (22.22%)
    3 / 19 (15.79%)
    5 / 33 (15.15%)
    2 / 6 (33.33%)
         occurrences all number
    2
    2
    4
    13
    5
    0
    1
    2
    6
    5
    2
    Back pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    3 / 14 (21.43%)
    2 / 28 (7.14%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    1 / 19 (5.26%)
    3 / 33 (9.09%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    3
    2
    0
    0
    0
    1
    4
    1
    Bone disorder
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Myalgia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    3 / 21 (14.29%)
    1 / 14 (7.14%)
    5 / 28 (17.86%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    3 / 33 (9.09%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    35
    1
    9
    0
    0
    0
    0
    4
    0
    Musculoskeletal stiffness
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    1 / 21 (4.76%)
    0 / 14 (0.00%)
    2 / 28 (7.14%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    3
    0
    0
    0
    0
    0
    0
    Musculoskeletal pain
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 9 (11.11%)
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    1 / 9 (11.11%)
    1 / 19 (5.26%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    2
    0
    0
    0
    1
    1
    0
    0
    Musculoskeletal chest pain
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 9 (11.11%)
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Neck pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    1 / 21 (4.76%)
    1 / 14 (7.14%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    1 / 33 (3.03%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    0
    0
    0
    0
    1
    0
    Muscular weakness
         subjects affected / exposed
    1 / 3 (33.33%)
    1 / 9 (11.11%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    1 / 33 (3.03%)
    1 / 6 (16.67%)
         occurrences all number
    1
    2
    0
    0
    0
    0
    0
    0
    0
    2
    1
    Polyarthritis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    1 / 9 (11.11%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    Pain in extremity
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    2 / 28 (7.14%)
    1 / 4 (25.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    1 / 19 (5.26%)
    2 / 33 (6.06%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    1
    0
    0
    1
    4
    0
    Osteoarthritis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    2 / 28 (7.14%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    0
    0
    0
    0
    0
    Spinal pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    2 / 21 (9.52%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    0
    0
    0
    0
    0
    0
    Tendon disorder
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Infections and infestations
    Balanitis candida
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    COVID-19
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    3 / 14 (21.43%)
    2 / 28 (7.14%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    1 / 9 (11.11%)
    0 / 19 (0.00%)
    1 / 33 (3.03%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    3
    2
    0
    0
    1
    0
    1
    1
    Dengue fever
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    2 / 28 (7.14%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    0
    0
    0
    0
    0
    Gastrointestinal infection
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    1 / 15 (6.67%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Influenza
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    1 / 21 (4.76%)
    0 / 14 (0.00%)
    2 / 28 (7.14%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    2
    0
    2
    0
    0
    0
    0
    0
    0
    Infection
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    1 / 21 (4.76%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    1 / 9 (11.11%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    0
    0
    1
    0
    0
    0
    Gastroenteritis norovirus
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Eye infection
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    1 / 19 (5.26%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Herpes simplex reactivation
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    1 / 28 (3.57%)
    1 / 4 (25.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    1 / 19 (5.26%)
    1 / 33 (3.03%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    0
    0
    1
    1
    0
    Herpes zoster
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    1 / 21 (4.76%)
    1 / 14 (7.14%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    0
    0
    0
    0
    0
    0
    Kidney infection
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    1 / 9 (11.11%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    Paronychia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    1 / 19 (5.26%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Oral herpes
         subjects affected / exposed
    0 / 3 (0.00%)
    2 / 9 (22.22%)
    2 / 21 (9.52%)
    2 / 14 (14.29%)
    0 / 28 (0.00%)
    1 / 4 (25.00%)
    0 / 15 (0.00%)
    1 / 9 (11.11%)
    3 / 19 (15.79%)
    1 / 33 (3.03%)
    0 / 6 (0.00%)
         occurrences all number
    0
    3
    5
    2
    0
    2
    0
    1
    3
    1
    0
    Oral candidiasis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    1 / 9 (11.11%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    Nasopharyngitis
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 9 (11.11%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    1 / 33 (3.03%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Orchitis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Respiratory tract infection
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 9 (11.11%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    1 / 28 (3.57%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Pulpitis dental
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Pneumonia
         subjects affected / exposed
    1 / 3 (33.33%)
    1 / 9 (11.11%)
    1 / 21 (4.76%)
    1 / 14 (7.14%)
    2 / 28 (7.14%)
    1 / 4 (25.00%)
    1 / 15 (6.67%)
    0 / 9 (0.00%)
    1 / 19 (5.26%)
    1 / 33 (3.03%)
    0 / 6 (0.00%)
         occurrences all number
    1
    1
    2
    1
    2
    2
    1
    0
    1
    1
    0
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 9 (11.11%)
    1 / 21 (4.76%)
    1 / 14 (7.14%)
    2 / 28 (7.14%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    2
    1
    1
    2
    0
    0
    0
    0
    0
    0
    Urethritis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Urinary tract infection
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 9 (11.11%)
    6 / 21 (28.57%)
    1 / 14 (7.14%)
    5 / 28 (17.86%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    1 / 9 (11.11%)
    1 / 19 (5.26%)
    4 / 33 (12.12%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    10
    3
    7
    0
    0
    1
    1
    5
    0
    Sinusitis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Skin candida
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    1 / 19 (5.26%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Skin infection
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Tinea pedis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    1 / 19 (5.26%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Viral infection
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    1 / 33 (3.03%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    1
    Viral upper respiratory tract infection
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Metabolism and nutrition disorders
    Diabetes mellitus
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    1 / 21 (4.76%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    1 / 19 (5.26%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    2
    0
    0
    Dehydration
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    1 / 9 (11.11%)
    1 / 19 (5.26%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    2
    2
    0
    0
    Decreased appetite
         subjects affected / exposed
    0 / 3 (0.00%)
    4 / 9 (44.44%)
    4 / 21 (19.05%)
    1 / 14 (7.14%)
    5 / 28 (17.86%)
    3 / 4 (75.00%)
    1 / 15 (6.67%)
    3 / 9 (33.33%)
    6 / 19 (31.58%)
    10 / 33 (30.30%)
    0 / 6 (0.00%)
         occurrences all number
    0
    6
    4
    1
    6
    4
    1
    4
    7
    12
    0
    Abnormal weight gain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    2 / 28 (7.14%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    4
    0
    0
    0
    0
    0
    0
    Abnormal loss of weight
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 9 (11.11%)
    3 / 21 (14.29%)
    1 / 14 (7.14%)
    3 / 28 (10.71%)
    1 / 4 (25.00%)
    0 / 15 (0.00%)
    1 / 9 (11.11%)
    1 / 19 (5.26%)
    1 / 33 (3.03%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    4
    1
    3
    1
    0
    1
    1
    1
    0
    Hypochloraemia
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 9 (11.11%)
    1 / 21 (4.76%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    17
    0
    0
    0
    0
    0
    0
    0
    0
    Hypocalcaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 9 (11.11%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    1 / 4 (25.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    1 / 19 (5.26%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    3
    0
    0
    0
    1
    0
    0
    2
    0
    0
    Hypoalbuminaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    2 / 9 (22.22%)
    1 / 21 (4.76%)
    2 / 14 (14.29%)
    3 / 28 (10.71%)
    3 / 4 (75.00%)
    2 / 15 (13.33%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    2 / 33 (6.06%)
    0 / 6 (0.00%)
         occurrences all number
    0
    2
    1
    9
    3
    3
    3
    0
    0
    3
    0
    Hyperuricaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    1 / 19 (5.26%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    1
    0
    0
    Hyperphosphataemia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Hypertriglyceridaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 9 (11.11%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Hyperglycaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    2 / 21 (9.52%)
    2 / 14 (14.29%)
    2 / 28 (7.14%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    1 / 33 (3.03%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    3
    2
    2
    0
    0
    0
    0
    2
    0
    Steroid diabetes
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 9 (11.11%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Hypophosphataemia
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 9 (11.11%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    2 / 33 (6.06%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    3
    0
    Hyponatraemia
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 9 (11.11%)
    2 / 21 (9.52%)
    1 / 14 (7.14%)
    1 / 28 (3.57%)
    0 / 4 (0.00%)
    1 / 15 (6.67%)
    1 / 9 (11.11%)
    0 / 19 (0.00%)
    2 / 33 (6.06%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    20
    1
    2
    0
    3
    1
    0
    4
    0
    Hypomagnesaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 9 (11.11%)
    2 / 21 (9.52%)
    1 / 14 (7.14%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    1 / 9 (11.11%)
    1 / 19 (5.26%)
    3 / 33 (9.09%)
    1 / 6 (16.67%)
         occurrences all number
    0
    4
    3
    2
    0
    0
    0
    1
    1
    4
    1
    Hypokalaemia
         subjects affected / exposed
    1 / 3 (33.33%)
    2 / 9 (22.22%)
    1 / 21 (4.76%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    2 / 15 (13.33%)
    1 / 9 (11.11%)
    5 / 19 (26.32%)
    3 / 33 (9.09%)
    1 / 6 (16.67%)
         occurrences all number
    2
    5
    3
    0
    0
    0
    4
    2
    7
    4
    1
    Hypoproteinaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 9 (11.11%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Type 2 diabetes mellitus
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 9 (11.11%)
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 4 (0.00%)
    0 / 15 (0.00%)
    0 / 9 (0.00%)
    0 / 19 (0.00%)
    0 / 33 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    22 Apr 2020
    The following changes were made as per amendment 01: 1. Modified inclusion and exclusion criteria. 2. Added a 90-day follow-up visit after last dose with the study treatment to capture any late-onset immune-related AEs. 3. Added AESI definition, procedure for recording and reporting AESIs, and monitoring of AESIs.
    10 Feb 2021
    The following changes were made as per amendment 02: 1.Modified inclusion criteria. 2. Added DCR, DRR, TTP, and OS as secondary endpoints for disclosure for phase 2.
    23 Apr 2021
    The following changes were made as per amendment 03: 1. Incorporated additional local laboratory assessments for safety during Cycle 1. 2. Provided guidance on COVID-19 vaccination and procedures during the trial.
    09 Sep 2021
    The primary reason for amendment 04 was to update the translational strategy for sample collection for analysis of biomarkers in phase 2.
    01 Jul 2022
    The primary reason for amendment 05 was to expand phase 2 enrollment in Cohort A to evaluate the dose regimen of subasumstat at 120 mg QW in addition to the 90 mg BIW dose regimen.
    22 Jun 2023
    The primary reason for amendment 06 was to remove nonsquamous NSCLC, SCLC, and MSI-H/dMMR CRC populations.

    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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    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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