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    Clinical Trial Results:
    A Phase 1 / 2 Open Label, Multi-Arm, Multicenter Study of MK-1308 in Combination with Pembrolizumab in Subjects with Advanced Solid Tumors

    Summary
    EudraCT number
    		 2019-003703-35
    Trial protocol
    		 PL   GR   IT  
    Global end of trial date
    08 Apr 2024

    Results information
    Results version number
    		 v1(current)
    This version publication date
    06 Apr 2025
    First version publication date
    06 Apr 2025
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    MK-1308-001
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Merck Sharp & Dohme LLC
    Sponsor organisation address
    126 East Lincoln Avenue, P.O. Box 2000, Rahway, NJ, United States, 07065
    Public contact
    Clinical Trials Disclosure, Merck Sharp & Dohme LLC, ClinicalTrialsDisclosure@merck.com
    Scientific contact
    Clinical Trials Disclosure, Merck Sharp & Dohme LLC, ClinicalTrialsDisclosure@merck.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
    08 Apr 2024
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    08 Apr 2024
    Global end of trial reached?
    Yes
    Global end of trial date
    08 Apr 2024
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    This study assessed the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of escalating doses of quavonlimab when used in combination with pembrolizumab in participants with advanced solid tumors.
    Protection of trial subjects
    This study was conducted in conformance with Good Clinical Practice standards and applicable country and/or local statutes and regulations regarding ethical committee review, informed consent, and the protection of human subjects participating in biomedical research.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    02 Jul 2017
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Australia: 43
    Country: Number of subjects enrolled
    Canada: 9
    Country: Number of subjects enrolled
    Chile: 5
    Country: Number of subjects enrolled
    China: 20
    Country: Number of subjects enrolled
    France: 19
    Country: Number of subjects enrolled
    Greece: 13
    Country: Number of subjects enrolled
    Israel: 66
    Country: Number of subjects enrolled
    Italy: 11
    Country: Number of subjects enrolled
    Japan: 17
    Country: Number of subjects enrolled
    Korea, Republic of: 89
    Country: Number of subjects enrolled
    New Zealand: 25
    Country: Number of subjects enrolled
    Poland: 18
    Country: Number of subjects enrolled
    Spain: 23
    Country: Number of subjects enrolled
    United States: 57
    Worldwide total number of subjects
    415
    EEA total number of subjects
    84
    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)
    208
    From 65 to 84 years
    205
    85 years and over
    2

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 This study was conducted at 53 centers in 16 countries

    Pre-assignment
    Screening details
    		 Per protocol, participants who showed blinded independent central review (BICR) - verified radiographical-progressive disease in Arm G were eligible to crossover to combination arm (MK-1308 25 mg + Pembrolizumab 400 mg Switchover) upon consultation with the Sponsor.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Non-randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Cohort 1: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W
    Arm description
    		 On cycle 1, day 1 of the dose escalation phase, participants with advanced solid tumors received 25 mg quavonlimab (MK-1308) monotherapy followed by 25 mg quavonlimab in combination with 200 mg pembrolizumab (pembro) every 3 weeks (Q3W) for cycles 2-5. Participants then received 200 mg pembrolizumab monotherapy Q3W starting on Cycle 6, for up to 35 cycles total (up to approximately 24 months).
    Arm type
    		 Experimental

    Investigational medicinal product name
    Pembrolizumab
    Investigational medicinal product code
    Other name
    MK-3475, Keytruda®
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    200 mg Q3W for 24 months

    Investigational medicinal product name
    MK-1308
    Investigational medicinal product code
    Other name
    Quavonlimab
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    25 mg every 3 weeks (Q3W) for 24 months

    Arm title
    		 Cohort 2: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W
    Arm description
    		 On cycle 1, day 1 of the dose escalation phase, participants with advanced solid tumor except non–small cell lung cancer (NSCLC) received 75 mg quavonlimab monotherapy followed by 75 mg quavonlimab in combination with 200 mg pembrolizumab Q3W for cycles 2-5. Participants then received 200 mg pembrolizumab monotherapy Q3W starting on Cycle 6, for up to 35 cycles total (up to approximately 24 months).
    Arm type
    		 Experimental

    Investigational medicinal product name
    Pembrolizumab
    Investigational medicinal product code
    Other name
    MK-3475, Keytruda®
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    200 mg Q3W for 24 months

    Investigational medicinal product name
    MK-1308
    Investigational medicinal product code
    Other name
    Quavonlimab
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    75 mg Q3W for 24 months

    Arm title
    		 Cohort 3: MK-1308 200 mg Q3W + Pembro. 200 mg Q3W
    Arm description
    		 On cycle 1, day 1 of the dose escalation phase, participants with advanced solid tumor except non–small cell lung cancer (NSCLC) received 200 mg quavonlimab monotherapy followed by 200 mg quavonlimab in combination with 200 mg pembrolizumab Q3W for cycles 2-5. Participants then received 200 mg pembrolizumab monotherapy Q3W starting on Cycle 6, for up to 35 cycles total (up to approximately 24 months).
    Arm type
    		 Experimental

    Investigational medicinal product name
    Pembrolizumab
    Investigational medicinal product code
    Other name
    MK-3475, Keytruda®
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    200 mg Q3W for 24 months

    Investigational medicinal product name
    MK-1308
    Investigational medicinal product code
    Other name
    Quavonlimab
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    200 mg Q3W for 24 months

    Arm title
    		 Arm A: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W
    Arm description
    		 On cycle 1, day 1 of the dose confirmation phase and during all subsequent cycles, participants with advanced/metastatic NSCLC received 25 mg quavonlimab in combination with 200 mg pembrolizumab Q3W. Participants were treated for 35 cycles total (up to approximately 24 months).
    Arm type
    		 Experimental

    Investigational medicinal product name
    Pembrolizumab
    Investigational medicinal product code
    Other name
    MK-3475, Keytruda®
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    200 mg Q3W for 24 months

    Investigational medicinal product name
    MK-1308
    Investigational medicinal product code
    Other name
    Quavonlimab
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    25 mg Q3W for 24 months

    Arm title
    		 Arm B: MK-1308 25 mg Q6W + Pembro. 200 mg Q3W
    Arm description
    		 On cycle 1, day 1 of the dose confirmation phase, participants with advanced/metastatic NSCLC received 25 mg quavonlimab in combination with 200 mg pembrolizumab Q3W. On all subsequent cycles, participants received 200 mg pembrolizumab Q3W and 25 mg quavonlimab every 6 weeks (Q6W). Participants were treated for up to 35 cycles total (up to approximately 24 months).
    Arm type
    		 Experimental

    Investigational medicinal product name
    Pembrolizumab
    Investigational medicinal product code
    Other name
    MK-3475, Keytruda®
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    200 mg Q3W for 24 months

    Investigational medicinal product name
    MK-1308
    Investigational medicinal product code
    Other name
    Quavonlimab
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    25 mg Q6W for 24 months

    Arm title
    		 Arm C: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W
    Arm description
    		 On cycle 1, day 1 of the dose confirmation phase, participants with advanced/metastatic NSCLC received 75 mg quavonlimab in combination with 200 mg pembrolizumab Q3W. On all subsequent cycles, participants received 200 mg pembrolizumab Q3W and 75 mg quavonlimab Q6W. Participants were treated for 35 cycles total (up to approximately 24 months).
    Arm type
    		 Experimental

    Investigational medicinal product name
    MK-1308
    Investigational medicinal product code
    Other name
    Quavonlimab
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    75 mg Q6W for 24 months

    Investigational medicinal product name
    Pembrolizumab
    Investigational medicinal product code
    Other name
    MK-3475, Keytruda®
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    200 mg Q3W for 24 months

    Arm title
    		 Arm D: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W
    Arm description
    		 On cycle 1, day 1 of the dose confirmation phase, participants with advanced/metastatic small cell lung cancer (SCLC) received 75 mg quavonlimab in combination with 200 mg pembrolizumab Q3W. On all subsequent cycles, participants received 200 mg pembrolizumab Q3W and 75 mg quavonlimab Q6W. Participants were treated for 35 cycles total (up to approximately 24 months).
    Arm type
    		 Experimental

    Investigational medicinal product name
    Pembrolizumab
    Investigational medicinal product code
    Other name
    MK-3475, Keytruda®
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    200 mg Q3W for 24 months

    Investigational medicinal product name
    MK-1308
    Investigational medicinal product code
    Other name
    Quavonlimab
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    75 mg Q6W for 24 months

    Arm title
    		 Arm E: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W
    Arm description
    		 On cycle 1, day 1 of the dose confirmation phase and during all subsequent cycles, participants with NSCLC received 75 mg quavonlimab in combination with 200 mg pembrolizumab Q3W. Participants were treated for 35 cycles total (up to approximately 24 months).
    Arm type
    		 Experimental

    Investigational medicinal product name
    Pembrolizumab
    Investigational medicinal product code
    Other name
    MK-3475, Keytruda®
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    200 mg Q3W for 24 months

    Investigational medicinal product name
    MK-1308
    Investigational medicinal product code
    Other name
    Quavonlimab
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    75 mg Q3W for 24 months

    Arm title
    		 Arm F: MK-1308 25 mg Q6W + Pembro. 400 mg Q6W Co-admin
    Arm description
    		 On cycle 1, day 1 of the efficacy expansion phase and during all subsequent cycles, participants with programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) refractory melanoma received 25 mg quavonlimab in combination with 400 mg pembrolizumab. Both quavonlimab and pembrolizumab were administered Q6W for 24 months.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Pembrolizumab
    Investigational medicinal product code
    Other name
    MK-3475, Keytruda®
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    400 mg Q6W for 24 months

    Investigational medicinal product name
    MK-1308
    Investigational medicinal product code
    Other name
    Quavonlimab
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    25 mg Q6W for 24 months

    Arm title
    		 Arm G: MK-1308 25 mg Q6W
    Arm description
    		 ‌On cycle 1, day 1 of the efficacy expansion phase and during all subsequent cycles, participants with PD-1/PD-L1 refractory melanoma received 25 mg quavonlimab Q6W for up to 24 months.
    Arm type
    		 Experimental

    Investigational medicinal product name
    MK-1308
    Investigational medicinal product code
    Other name
    Quavonlimab
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    25 mg Q6W for 24 months

    Arm title
    		 Arm I: MK-1308A Q6W (Co-form)
    Arm description
    		 On cycle 1, day 1 of the coformulation (Co-form) phase and during all subsequent cycles, participants with advanced/metastatic solid tumors received 400 mg pembrolizumab co-formulated with 25 mg quavonlimab (MK-1308A) Q6W for 24 months.
    Arm type
    		 Experimental

    Investigational medicinal product name
    MK-1308A
    Investigational medicinal product code
    Other name
    Quavonlimab
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    25 mg Q6W for 24 months

    Investigational medicinal product name
    Pembrolizumab
    Investigational medicinal product code
    Other name
    MK-3475, Keytruda®
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    400 mg Q6W for 24 months

    Arm title
    		 Arm K: MK-1308A Q6W (Co-form)
    Arm description
    		 On cycle 1, day 1 of the coformulation phase and during all subsequent cycles, participants in mainland China with advanced/metastatic solid tumors received 400 mg pembrolizumab co-formulated with 25 mg quavonlimab (MK-1308A) Q6W for 24 months.
    Arm type
    		 Experimental

    Investigational medicinal product name
    MK-1308A
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    25 mg Q6W for 24 months

    Investigational medicinal product name
    Pembrolizumab
    Investigational medicinal product code
    Other name
    MK-3475, Keytruda®
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    400 mg Q6W for 24 months

    Number of subjects in period 1
    		Cohort 1: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W Cohort 2: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W Cohort 3: MK-1308 200 mg Q3W + Pembro. 200 mg Q3W Arm A: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W Arm B: MK-1308 25 mg Q6W + Pembro. 200 mg Q3W Arm C: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W Arm D: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W Arm E: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W Arm F: MK-1308 25 mg Q6W + Pembro. 400 mg Q6W Co-admin Arm G: MK-1308 25 mg Q6W Arm I: MK-1308A Q6W (Co-form) Arm K: MK-1308A Q6W (Co-form)
    Started
    14
    18
    8
    40
    40
    41
    40
    14
    111
    40
    29
    20
    Switched over to combination treatment
    0
    0
    0
    0
    0
    0
    0
    0
    0
    21
    0
    0
    Treated
    14
    17
    8
    40
    40
    40
    40
    14
    111
    40
    29
    20
    Completed
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Not completed
    14
    18
    8
    40
    40
    41
    40
    14
    111
    40
    29
    20
         Death
    12
    17
    7
    32
    29
    30
    33
    9
    84
    33
    22
    15
         Randomized by mistake without Study Treatment
    -
    1
    -
    -
    -
    1
    -
    -
    -
    -
    -
    -
         Withdrawal by Parent/Guardian
    -
    -
    -
    -
    -
    -
    -
    1
    -
    -
    -
    -
         Withdrawal by Subject
    1
    -
    -
    4
    2
    2
    5
    -
    3
    -
    -
    -
         Sponsor Decision
    -
    -
    1
    3
    9
    7
    2
    4
    23
    6
    7
    5
         Lost to follow-up
    1
    -
    -
    1
    -
    1
    -
    -
    1
    1
    -
    -

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Cohort 1: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W
    Reporting group description
    		 On cycle 1, day 1 of the dose escalation phase, participants with advanced solid tumors received 25 mg quavonlimab (MK-1308) monotherapy followed by 25 mg quavonlimab in combination with 200 mg pembrolizumab (pembro) every 3 weeks (Q3W) for cycles 2-5. Participants then received 200 mg pembrolizumab monotherapy Q3W starting on Cycle 6, for up to 35 cycles total (up to approximately 24 months).

    Reporting group title
    Cohort 2: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W
    Reporting group description
    		 On cycle 1, day 1 of the dose escalation phase, participants with advanced solid tumor except non–small cell lung cancer (NSCLC) received 75 mg quavonlimab monotherapy followed by 75 mg quavonlimab in combination with 200 mg pembrolizumab Q3W for cycles 2-5. Participants then received 200 mg pembrolizumab monotherapy Q3W starting on Cycle 6, for up to 35 cycles total (up to approximately 24 months).

    Reporting group title
    Cohort 3: MK-1308 200 mg Q3W + Pembro. 200 mg Q3W
    Reporting group description
    		 On cycle 1, day 1 of the dose escalation phase, participants with advanced solid tumor except non–small cell lung cancer (NSCLC) received 200 mg quavonlimab monotherapy followed by 200 mg quavonlimab in combination with 200 mg pembrolizumab Q3W for cycles 2-5. Participants then received 200 mg pembrolizumab monotherapy Q3W starting on Cycle 6, for up to 35 cycles total (up to approximately 24 months).

    Reporting group title
    Arm A: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W
    Reporting group description
    		 On cycle 1, day 1 of the dose confirmation phase and during all subsequent cycles, participants with advanced/metastatic NSCLC received 25 mg quavonlimab in combination with 200 mg pembrolizumab Q3W. Participants were treated for 35 cycles total (up to approximately 24 months).

    Reporting group title
    Arm B: MK-1308 25 mg Q6W + Pembro. 200 mg Q3W
    Reporting group description
    		 On cycle 1, day 1 of the dose confirmation phase, participants with advanced/metastatic NSCLC received 25 mg quavonlimab in combination with 200 mg pembrolizumab Q3W. On all subsequent cycles, participants received 200 mg pembrolizumab Q3W and 25 mg quavonlimab every 6 weeks (Q6W). Participants were treated for up to 35 cycles total (up to approximately 24 months).

    Reporting group title
    Arm C: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W
    Reporting group description
    		 On cycle 1, day 1 of the dose confirmation phase, participants with advanced/metastatic NSCLC received 75 mg quavonlimab in combination with 200 mg pembrolizumab Q3W. On all subsequent cycles, participants received 200 mg pembrolizumab Q3W and 75 mg quavonlimab Q6W. Participants were treated for 35 cycles total (up to approximately 24 months).

    Reporting group title
    Arm D: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W
    Reporting group description
    		 On cycle 1, day 1 of the dose confirmation phase, participants with advanced/metastatic small cell lung cancer (SCLC) received 75 mg quavonlimab in combination with 200 mg pembrolizumab Q3W. On all subsequent cycles, participants received 200 mg pembrolizumab Q3W and 75 mg quavonlimab Q6W. Participants were treated for 35 cycles total (up to approximately 24 months).

    Reporting group title
    Arm E: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W
    Reporting group description
    		 On cycle 1, day 1 of the dose confirmation phase and during all subsequent cycles, participants with NSCLC received 75 mg quavonlimab in combination with 200 mg pembrolizumab Q3W. Participants were treated for 35 cycles total (up to approximately 24 months).

    Reporting group title
    Arm F: MK-1308 25 mg Q6W + Pembro. 400 mg Q6W Co-admin
    Reporting group description
    		 On cycle 1, day 1 of the efficacy expansion phase and during all subsequent cycles, participants with programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) refractory melanoma received 25 mg quavonlimab in combination with 400 mg pembrolizumab. Both quavonlimab and pembrolizumab were administered Q6W for 24 months.

    Reporting group title
    Arm G: MK-1308 25 mg Q6W
    Reporting group description
    		 ‌On cycle 1, day 1 of the efficacy expansion phase and during all subsequent cycles, participants with PD-1/PD-L1 refractory melanoma received 25 mg quavonlimab Q6W for up to 24 months.

    Reporting group title
    Arm I: MK-1308A Q6W (Co-form)
    Reporting group description
    		 On cycle 1, day 1 of the coformulation (Co-form) phase and during all subsequent cycles, participants with advanced/metastatic solid tumors received 400 mg pembrolizumab co-formulated with 25 mg quavonlimab (MK-1308A) Q6W for 24 months.

    Reporting group title
    Arm K: MK-1308A Q6W (Co-form)
    Reporting group description
    		 On cycle 1, day 1 of the coformulation phase and during all subsequent cycles, participants in mainland China with advanced/metastatic solid tumors received 400 mg pembrolizumab co-formulated with 25 mg quavonlimab (MK-1308A) Q6W for 24 months.

    Reporting group values
    		 Cohort 1: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W Cohort 2: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W Cohort 3: MK-1308 200 mg Q3W + Pembro. 200 mg Q3W Arm A: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W Arm B: MK-1308 25 mg Q6W + Pembro. 200 mg Q3W Arm C: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W Arm D: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W Arm E: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W Arm F: MK-1308 25 mg Q6W + Pembro. 400 mg Q6W Co-admin Arm G: MK-1308 25 mg Q6W Arm I: MK-1308A Q6W (Co-form) Arm K: MK-1308A Q6W (Co-form) Total
    Number of subjects
    		 14 18 8 40 40 41 40 14 111 40 29 20 415
    Age Categorical
    Units: Subjects
        In utero
    		 0 0 0 0 0 0 0 0 0 0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0 0 0 0 0 0 0 0 0 0 0
        Newborns (0-27 days)
    		 0 0 0 0 0 0 0 0 0 0 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0 0 0 0 0 0 0 0 0 0 0
        Children (2-11 years)
    		 0 0 0 0 0 0 0 0 0 0 0 0 0
        Adolescents (12-17 years)
    		 0 0 0 0 0 0 0 0 0 0 0 0 0
        Adults (18-64 years)
    		 8 12 2 23 18 17 17 4 53 24 16 14 208
        From 65-84 years
    		 6 6 6 17 21 24 23 10 57 16 13 6 205
        85 years and over
    		 0 0 0 0 1 0 0 0 1 0 0 0 2
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 57.1 ( 15.4 ) 57.6 ( 11.3 ) 66.8 ( 3.2 ) 64.2 ( 10.9 ) 63.7 ( 11.4 ) 66.3 ( 9.2 ) 64.1 ( 8.3 ) 68.0 ( 11.5 ) 63.5 ( 12.6 ) 59.7 ( 11.6 ) 63.7 ( 11.5 ) 56.6 ( 11.9 ) -
    Gender Categorical
    Units: Subjects
        Female
    		 11 10 4 10 12 17 16 5 34 18 13 8 158
        Male
    		 3 8 4 30 28 24 24 9 77 22 16 12 257
    Race
    Units: Subjects
        Asian
    		 0 0 0 30 26 26 16 8 3 0 3 20 132
        Black Or African American
    		 0 1 0 0 0 1 1 0 0 0 0 0 3
        Native Hawaiian Or Other Pacific Islander
    		 0 0 0 0 0 0 0 0 0 0 3 0 3
        White
    		 14 17 8 10 14 14 23 6 105 38 23 0 272
        Missing
    		 0 0 0 0 0 0 0 0 3 2 0 0 5
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    		 1 1 1 0 3 0 0 0 1 4 0 0 11
        Not Hispanic or Latino
    		 13 17 7 40 37 41 39 13 102 33 29 20 391
        Not Reported
    		 0 0 0 0 0 0 0 1 6 2 0 0 9
        Unknown
    		 0 0 0 0 0 0 1 0 2 1 0 0 4

    End points

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    End points reporting groups
    Reporting group title
    Cohort 1: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W
    Reporting group description
    		 On cycle 1, day 1 of the dose escalation phase, participants with advanced solid tumors received 25 mg quavonlimab (MK-1308) monotherapy followed by 25 mg quavonlimab in combination with 200 mg pembrolizumab (pembro) every 3 weeks (Q3W) for cycles 2-5. Participants then received 200 mg pembrolizumab monotherapy Q3W starting on Cycle 6, for up to 35 cycles total (up to approximately 24 months).

    Reporting group title
    Cohort 2: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W
    Reporting group description
    		 On cycle 1, day 1 of the dose escalation phase, participants with advanced solid tumor except non–small cell lung cancer (NSCLC) received 75 mg quavonlimab monotherapy followed by 75 mg quavonlimab in combination with 200 mg pembrolizumab Q3W for cycles 2-5. Participants then received 200 mg pembrolizumab monotherapy Q3W starting on Cycle 6, for up to 35 cycles total (up to approximately 24 months).

    Reporting group title
    Cohort 3: MK-1308 200 mg Q3W + Pembro. 200 mg Q3W
    Reporting group description
    		 On cycle 1, day 1 of the dose escalation phase, participants with advanced solid tumor except non–small cell lung cancer (NSCLC) received 200 mg quavonlimab monotherapy followed by 200 mg quavonlimab in combination with 200 mg pembrolizumab Q3W for cycles 2-5. Participants then received 200 mg pembrolizumab monotherapy Q3W starting on Cycle 6, for up to 35 cycles total (up to approximately 24 months).

    Reporting group title
    Arm A: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W
    Reporting group description
    		 On cycle 1, day 1 of the dose confirmation phase and during all subsequent cycles, participants with advanced/metastatic NSCLC received 25 mg quavonlimab in combination with 200 mg pembrolizumab Q3W. Participants were treated for 35 cycles total (up to approximately 24 months).

    Reporting group title
    Arm B: MK-1308 25 mg Q6W + Pembro. 200 mg Q3W
    Reporting group description
    		 On cycle 1, day 1 of the dose confirmation phase, participants with advanced/metastatic NSCLC received 25 mg quavonlimab in combination with 200 mg pembrolizumab Q3W. On all subsequent cycles, participants received 200 mg pembrolizumab Q3W and 25 mg quavonlimab every 6 weeks (Q6W). Participants were treated for up to 35 cycles total (up to approximately 24 months).

    Reporting group title
    Arm C: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W
    Reporting group description
    		 On cycle 1, day 1 of the dose confirmation phase, participants with advanced/metastatic NSCLC received 75 mg quavonlimab in combination with 200 mg pembrolizumab Q3W. On all subsequent cycles, participants received 200 mg pembrolizumab Q3W and 75 mg quavonlimab Q6W. Participants were treated for 35 cycles total (up to approximately 24 months).

    Reporting group title
    Arm D: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W
    Reporting group description
    		 On cycle 1, day 1 of the dose confirmation phase, participants with advanced/metastatic small cell lung cancer (SCLC) received 75 mg quavonlimab in combination with 200 mg pembrolizumab Q3W. On all subsequent cycles, participants received 200 mg pembrolizumab Q3W and 75 mg quavonlimab Q6W. Participants were treated for 35 cycles total (up to approximately 24 months).

    Reporting group title
    Arm E: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W
    Reporting group description
    		 On cycle 1, day 1 of the dose confirmation phase and during all subsequent cycles, participants with NSCLC received 75 mg quavonlimab in combination with 200 mg pembrolizumab Q3W. Participants were treated for 35 cycles total (up to approximately 24 months).

    Reporting group title
    Arm F: MK-1308 25 mg Q6W + Pembro. 400 mg Q6W Co-admin
    Reporting group description
    		 On cycle 1, day 1 of the efficacy expansion phase and during all subsequent cycles, participants with programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) refractory melanoma received 25 mg quavonlimab in combination with 400 mg pembrolizumab. Both quavonlimab and pembrolizumab were administered Q6W for 24 months.

    Reporting group title
    Arm G: MK-1308 25 mg Q6W
    Reporting group description
    		 ‌On cycle 1, day 1 of the efficacy expansion phase and during all subsequent cycles, participants with PD-1/PD-L1 refractory melanoma received 25 mg quavonlimab Q6W for up to 24 months.

    Reporting group title
    Arm I: MK-1308A Q6W (Co-form)
    Reporting group description
    		 On cycle 1, day 1 of the coformulation (Co-form) phase and during all subsequent cycles, participants with advanced/metastatic solid tumors received 400 mg pembrolizumab co-formulated with 25 mg quavonlimab (MK-1308A) Q6W for 24 months.

    Reporting group title
    Arm K: MK-1308A Q6W (Co-form)
    Reporting group description
    		 On cycle 1, day 1 of the coformulation phase and during all subsequent cycles, participants in mainland China with advanced/metastatic solid tumors received 400 mg pembrolizumab co-formulated with 25 mg quavonlimab (MK-1308A) Q6W for 24 months.

    Subject analysis set title
    Arm F Crossover: MK-1308 25mg Q6W + Pembro. 400mg Q6W Co-admin
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Participants who demonstrated radiographically confirmed progressive disease in Arm G and switched over to combination therapy received 25 mg quavonlimab in combination with 400 mg pembrolizumab. Both quavonlimab and pembrolizumab were administered Q6W for 24 months.

    Primary: Percentage of participants with ≥1 Dose Limiting Toxicity (DLT)

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    End point title
    		 Percentage of participants with ≥1 Dose Limiting Toxicity (DLT) [1] [2]
    End point description
    DLTs include Grade (Gr)4 non-hematologic toxicity (not laboratory); Gr 4 hematologic toxicity lasting ≥7 days (except thrombocytopenia); most non-hematologic AEs ≥ Gr 3 in severity; any Gr 3 or Gr 4 non-hematologic laboratory value that requires clinically significant medical intervention, leads to hospitalization, persists for >1 week, or results in a drug-induced liver injury; Gr 3 or Gr 4 febrile neutropenia; a prolonged delay in initiating Cycle 2 or 3 of Dose Escalation or Cycle 2 of Dose Confirmation due to treatment-related toxicity; any treatment-related toxicity that causes the participant to discontinue treatment during the DLT observation period, and Gr 5 toxicity. Analysis population consists of all participants who received ≥1 dose of study treatment who finished the DLT observation period in the dose escalation and dose confirmation phase only. Per protocol, no analysis was planned for arms F, G, I, K and participants crossing over into MK-1308 25 mg and Pembrolizumab.
    End point type
    Primary
    End point timeframe
    Up to 6 weeks
    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: No statistical analyses were planned for this endpoint.
    [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Per protocol, no analysis was planned for arm G and participants crossing over into MK-1308 25 mg and Pembrolizumab.
    End point values
    		 Cohort 1: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W Cohort 2: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W Cohort 3: MK-1308 200 mg Q3W + Pembro. 200 mg Q3W Arm A: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W Arm B: MK-1308 25 mg Q6W + Pembro. 200 mg Q3W Arm C: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W Arm D: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W Arm E: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W
    Number of subjects analysed
    13
    15
    7
    40
    40
    40
    40
    14
    Units: Percentage of Participants
        number (confidence interval 80%)
    0.0 (0.0 to 10.9)
    13.3 (4.9 to 26.6)
    0.0 (0.0 to 18.2)
    7.5 (3.3 to 14.0)
    5.0 (1.7 to 10.8)
    10.0 (5.0 to 17.1)
    10.0 (5.0 to 17.1)
    7.1 (1.4 to 19.4)
    No statistical analyses for this end point

    Primary: Number of participants with ≥1 adverse event (AE)

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    End point title
    		 Number of participants with ≥1 adverse event (AE) [3]
    End point description
    An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product temporally associated with the use of study treatment, whether or not considered related to the study treatment. The analysis population included all participants who received at least one dose of study intervention in the dose escalation (Cohorts 1-3), confirmation (arms A,B,C,D,E), efficacy expansion (arm F, G) and coformulation phases (arms I,K) only. Per protocol, no analysis was planned for participants crossing over into MK-1308 25 mg and Pembrolizumab. The number of participants who experienced an AE are presented.
    End point type
    Primary
    End point timeframe
    Up to approximately 77 months
    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: No statistical analyses were planned for this endpoint.
    End point values
    		 Cohort 1: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W Cohort 2: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W Cohort 3: MK-1308 200 mg Q3W + Pembro. 200 mg Q3W Arm A: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W Arm B: MK-1308 25 mg Q6W + Pembro. 200 mg Q3W Arm C: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W Arm D: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W Arm E: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W Arm F: MK-1308 25 mg Q6W + Pembro. 400 mg Q6W Co-admin Arm G: MK-1308 25 mg Q6W Arm I: MK-1308A Q6W (Co-form) Arm K: MK-1308A Q6W (Co-form)
    Number of subjects analysed
    14
    17
    8
    40
    40
    40
    40
    14
    111
    40
    29
    20
    Units: Participants
    14
    17
    8
    39
    38
    40
    38
    14
    104
    37
    28
    18
    No statistical analyses for this end point

    Primary: Number of participants discontinuing study treatment due to an AE

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    End point title
    		 Number of participants discontinuing study treatment due to an AE [4]
    End point description
    An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product temporally associated with the use of study treatment, whether or not considered related to the study treatment. The analysis population included all participants who received at least one dose of study intervention in the dose escalation (Cohorts 1-3), confirmation (arms A,B,C,D,E), efficacy expansion (arm F, G) and coformulation phases (arms I,K) only. Per protocol, no analysis was planned for participants crossing over into MK-1308 25 mg and Pembrolizumab. The number of participants who discontinued study treatment due to an AE are presented.
    End point type
    Primary
    End point timeframe
    Up to approximately 26 months
    Notes
    [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analyses were planned for this endpoint.
    End point values
    		 Cohort 1: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W Cohort 2: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W Cohort 3: MK-1308 200 mg Q3W + Pembro. 200 mg Q3W Arm A: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W Arm B: MK-1308 25 mg Q6W + Pembro. 200 mg Q3W Arm C: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W Arm D: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W Arm E: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W Arm F: MK-1308 25 mg Q6W + Pembro. 400 mg Q6W Co-admin Arm G: MK-1308 25 mg Q6W Arm I: MK-1308A Q6W (Co-form) Arm K: MK-1308A Q6W (Co-form)
    Number of subjects analysed
    14
    17
    8
    40
    40
    40
    40
    14
    111
    40
    29
    20
    Units: Participants
    1
    4
    3
    7
    7
    17
    7
    6
    14
    1
    4
    2
    No statistical analyses for this end point

    Primary: Efficacy Expansion: Objective Response Rate (ORR) as assessed by blinded independent central review (BICR) based on adjusted Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)

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    End point title
    		 Efficacy Expansion: Objective Response Rate (ORR) as assessed by blinded independent central review (BICR) based on adjusted Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) [5]
    End point description
    ORR is defined as the percentage of participants with Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per adjusted Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1). The percentage of participants who experience CR or PR in the concurrent randomized subset as assessed by Blinded Independent Central Review (BICR) will be presented. Per protocol, only data for arms F and G were presented for this endpoint. Analysis population consists of all participants with a baseline scan that demonstrated measurable disease and who were administered at least 1 dose of study intervention.
    End point type
    Primary
    End point timeframe
    Up to approximately 72 months
    Notes
    [5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Per protocol, no analysis was planned for arm G and participants crossing over into MK-1308 25 mg and Pembrolizumab.
    End point values
    		 Arm F: MK-1308 25 mg Q6W + Pembro. 400 mg Q6W Co-admin Arm G: MK-1308 25 mg Q6W
    Number of subjects analysed
    41
    40
    Units: Percentage of participants
        number (confidence interval 95%)
    4.9 (0.6 to 16.5)
    2.5 (0.1 to 13.2)
    Statistical analysis title
    		 Difference in Percentage
    Statistical analysis description
    Comparision based on Miettinen & Nurminen method
    Comparison groups
    Arm F: MK-1308 25 mg Q6W + Pembro. 400 mg Q6W Co-admin v Arm G: MK-1308 25 mg Q6W
    Number of subjects included in analysis
    81
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Difference in Percentage
    Point estimate
    2.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -8.7
         upper limit
    		 14.1

    Secondary: Area under the plasma concentration time curve (AUC) of pembrolizumab

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    End point title
    		 Area under the plasma concentration time curve (AUC) of pembrolizumab [6]
    End point description
    AUC was defined as a measure of pembrolizumab exposure that was calculated as the product of plasma drug concentration and time after drug administration. AUC determined by blood samples collected pre-dose and at designated timepoints post-dose are presented. The analysis population included all participants who complied with the protocol sufficiently to ensure that their data will be likely to show the effects of treatment, according to the underlying scientific model and had available data from at least 1 dose of study intervention. Per protocol, no analysis was planned for arm G and participants crossing over into MK-1308 25 mg and Pembrolizumab. AUC of pembrolizumab is presented. N = number of participants analyzed per cycle.
    End point type
    Secondary
    End point timeframe
    At designated time points up to - Cohorts 1-3: Day 15 Cycle 3, Arms A, B, C, D, E: Day 15 Cycle 3, Arm F: Day 21 Cycle 3, Arm I: Day 21 Cycle 3, Arm K: Day 21 Cycle 3. Each cycle is 21 days.
    Notes
    [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Per protocol, no analysis was planned for arm G and participants crossing over into MK-1308 25 mg and Pembrolizumab.
    End point values
    		 Cohort 1: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W Cohort 2: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W Cohort 3: MK-1308 200 mg Q3W + Pembro. 200 mg Q3W Arm A: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W Arm B: MK-1308 25 mg Q6W + Pembro. 200 mg Q3W Arm C: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W Arm D: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W Arm E: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W Arm F: MK-1308 25 mg Q6W + Pembro. 400 mg Q6W Co-admin Arm I: MK-1308A Q6W (Co-form) Arm K: MK-1308A Q6W (Co-form)
    Number of subjects analysed
    14 [7]
    17 [8]
    8 [9]
    40 [10]
    40 [11]
    40 [12]
    40 [13]
    14 [14]
    111 [15]
    29 [16]
    20 [17]
    Units: day*μg/mL
    geometric mean (geometric coefficient of variation)
        Cycle 1
    0 ( 0 )
    0 ( 0 )
    0 ( 0 )
    608 ( 24.6 )
    620 ( 25.9 )
    627 ( 20.6 )
    642 ( 23.9 )
    554 ( 15.6 )
    2050 ( 33.6 )
    2250 ( 18.7 )
    1610 ( 25.0 )
        Cycle 2
    729 ( 18.3 )
    546 ( 40.5 )
    727 ( 24.5 )
    788 ( 24.7 )
    854 ( 19.9 )
    822 ( 25.0 )
    877 ( 28.3 )
    794 ( 18.0 )
    2370 ( 40.6 )
    2820 ( 29.7 )
    1770 ( 34.4 )
        Cycle 3
    0 ( 0 )
    0 ( 0 )
    0 ( 0 )
    911 ( 22.7 )
    971 ( 22.9 )
    944 ( 26.0 )
    1050 ( 20.8 )
    872 ( 16.3 )
    2410 ( 29.5 )
    3410 ( 16.1 )
    2440 ( 39.8 )
    Notes
    [7] - N=0 for cycle 1, N=11 for cycle 2, N=0 for cycle 3.
    [8] - N=0 for cycle 1, N=8 for cycle 2, N=0 for cycle 3.
    [9] - N=0 for cycle 1, N=3 for cycle 2, N=0 for cycle 3.
    [10] - N=30 for cycle 1, N=30 for cycle 2, N=21 for cycle 3.
    [11] - N=34 for cycle 1, N=31 for cycle 2, N=27 for cycle 3.
    [12] - N=27 for cycle 1, N=24 for cycle 2, N=19 for cycle 3.
    [13] - N=28 for cycle 1, N=26 for cycle 2, N=15 for cycle 3.
    [14] - N=9 for cycle 1, N=9 for cycle 2, N=7 for cycle 3
    [15] - N=31 for cycle 1, N=18 for cycle 2, N=16 for cycle 3
    [16] - N=8 for cycle 1, N=5 for cycle 2, N=2 for cycle 3
    [17] - N=20 for cycle 1, N=16 for cycle 2, N=6 for cycle 3
    No statistical analyses for this end point

    Secondary: Maximum concentration (Cmax) of pembrolizumab

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    End point title
    		 Maximum concentration (Cmax) of pembrolizumab [18]
    End point description
    Cmax was defined as the maximum concentration of pembrolizumab observed in plasma. Cmax determined by blood samples collected pre-dose and at designated timepoints post-dose are presented. The analysis population included all participants who complied with the protocol sufficiently to ensure that their data will be likely to show the effects of treatment, according to the underlying scientific model and had available data from at least 1 dose of study intervention. Per protocol, no analysis was planned for arm G and participants crossing over into MK-1308 25 mg and Pembrolizumab. Cmax of pembrolizumab is presented. N = number of participants analyzed per cycle.
    End point type
    Secondary
    End point timeframe
    At designated time points up to - Cohorts 1-3: Day 15 Cycle 3, Arms A, B, C, D, E: Day 15 Cycle 3, Arm F: Day 21 Cycle 3, Arm I: Day 21 Cycle 3, Arm K: Day 21 Cycle 3. Each cycle is 21 days.
    Notes
    [18] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Per protocol, no analysis was planned for arm G and participants crossing over into MK-1308 25 mg and Pembrolizumab.
    End point values
    		 Cohort 1: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W Cohort 2: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W Cohort 3: MK-1308 200 mg Q3W + Pembro. 200 mg Q3W Arm A: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W Arm B: MK-1308 25 mg Q6W + Pembro. 200 mg Q3W Arm C: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W Arm D: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W Arm E: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W Arm F: MK-1308 25 mg Q6W + Pembro. 400 mg Q6W Co-admin Arm I: MK-1308A Q6W (Co-form) Arm K: MK-1308A Q6W (Co-form)
    Number of subjects analysed
    14 [19]
    17 [20]
    8 [21]
    40 [22]
    40 [23]
    40 [24]
    40 [25]
    14 [26]
    111 [27]
    29 [28]
    20 [29]
    Units: μg/mL
    geometric mean (geometric coefficient of variation)
        Cycle 1
    0.0 ( 0.0 )
    0.0 ( 0.0 )
    0.0 ( 0.0 )
    71.8 ( 24.0 )
    77.1 ( 26.7 )
    74.0 ( 27.8 )
    73.6 ( 22.3 )
    70.9 ( 35.3 )
    149 ( 29.1 )
    149 ( 23.8 )
    128 ( 21.9 )
        Cycle 2
    79.8 ( 31.3 )
    82.3 ( 32.3 )
    78.7 ( 32.4 )
    82.9 ( 20.2 )
    88.2 ( 20.9 )
    83.9 ( 23.2 )
    90.4 ( 23.7 )
    84.8 ( 18.6 )
    150 ( 28.9 )
    164 ( 22.8 )
    139 ( 20.5 )
        Cycle 3
    93.9 ( 21.0 )
    74.9 ( 28.1 )
    88.6 ( 12.2 )
    84.2 ( 16.9 )
    92.3 ( 27.5 )
    91.8 ( 21.7 )
    98.0 ( 27.4 )
    84.5 ( 13.8 )
    153 ( 22.1 )
    168 ( 22.3 )
    138 ( 31.1 )
    Notes
    [19] - N=0 for cycle 1, N=13 for cycle 2, N=10 for cycle 3.
    [20] - N=0 for cycle 1, N=13 for cycle 2, N=11 for cycle 3.
    [21] - N=0 for cycle 1, N=8 for cycle 2, N=3 for cycle 3.
    [22] - N=39 for cycle 1, N=34 for cycle 2, N=31 for cycle 3.
    [23] - N=40 for cycle 1, N=33 for cycle 2, N=32 for cycle 3.
    [24] - N=37 for cycle 1, N=30 for cycle 2, N=28 for cycle 3.
    [25] - N=39 for cycle 1, N=31 for cycle 2, N=26 for cycle 3.
    [26] - N=14 for cycle 1, N=10 for cycle 2, N=8 for cycle 3.
    [27] - N=105 for cycle 1, N=94 for cycle 2, N=63 for cycle 3.
    [28] - N=28 for cycle 1, N=21 for cycle 2, N=13 for cycle 3.
    [29] - N=20 for cycle 1, N=16 for cycle 2, N=12 for cycle 3.
    No statistical analyses for this end point

    Secondary: Minimum concentration (Cmin) of pembrolizumab

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    End point title
    		 Minimum concentration (Cmin) of pembrolizumab [30]
    End point description
    Cmin was defined as the minimum or "trough" concentration of pembrolizumab observed after its administration and just prior to the administration of a subsequent dose. Cmin determined by blood samples collected pre-dose and at designated timepoints post-dose are presented. The analysis population included all participants who complied with the protocol sufficiently to ensure that their data will be likely to show the effects of treatment, according to the underlying scientific model and had available data from at least 1 dose of study intervention. Per protocol, no analysis was planned for arm G and participants crossing over into MK-1308 25 mg and Pembrolizumab. Cmin of pembrolizumab is presented. N = number of participants analyzed per cycle.
    End point type
    Secondary
    End point timeframe
    At designated time points up to - Cohorts 1-3: Day 1 Cycle 4, Arms A, B, C, D, E: Day 15 Cycle 3, Arm F: Day 21 Cycle 3, Arm I: Day 21 Cycle 3, Arm K: Day 21 Cycle 3. Each cycle is 21 days.
    Notes
    [30] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Per protocol, no analysis was planned for arm G and participants crossing over into MK-1308 25 mg and Pembrolizumab.
    End point values
    		 Cohort 1: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W Cohort 2: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W Cohort 3: MK-1308 200 mg Q3W + Pembro. 200 mg Q3W Arm A: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W Arm B: MK-1308 25 mg Q6W + Pembro. 200 mg Q3W Arm C: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W Arm D: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W Arm E: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W Arm F: MK-1308 25 mg Q6W + Pembro. 400 mg Q6W Co-admin Arm I: MK-1308A Q6W (Co-form) Arm K: MK-1308A Q6W (Co-form)
    Number of subjects analysed
    14 [31]
    17 [32]
    8 [33]
    40 [34]
    40 [35]
    40 [36]
    40 [37]
    14 [38]
    111 [39]
    29 [40]
    20 [41]
    Units: μg/mL
    median (full range (min-max))
        Cycle 1
    0.00 (0.00 to 0.00)
    0.00 (0.00 to 0.00)
    0.00 (0.00 to 0.00)
    13.3 (0.00 to 22.3)
    13.1 (3.93 to 24.9)
    14.3 (5.59 to 90.4)
    15.6 (6.35 to 35.9)
    11.5 (4.77 to 18.0)
    21.9 (1.89 to 143)
    19.5 (7.25 to 35.8)
    14.4 (5.74 to 26.0)
        Cycle 2
    18.3 (11.3 to 27.8)
    11.3 (0.00 to 28.1)
    19.0 (9.21 to 24.6)
    19.6 (6.62 to 37.4)
    24.3 (9.06 to 34.6)
    20.4 (9.19 to 44.9)
    25.2 (10.1 to 55.1)
    18.9 (8.52 to 25.5)
    23.1 (0.0266 to 51.6)
    30.0 (16.2 to 60.4)
    22.5 (8.74 to 37.1)
        Cycle 3
    0.00 (0.00 to 0.00)
    0.00 (0.00 to 0.00)
    0.00 (0.00 to 0.00)
    25.7 (13.7 to 40.3)
    27.5 (12.4 to 42.2)
    25.5 (11.3 to 98.2)
    29.3 (10.4 to 56.7)
    27.7 (14.5 to 30.5)
    24.5 (2.22 to 127)
    34.0 (18.9 to 72.2)
    26.6 (7.74 to 32.6)
        Cycle 4
    34.3 (29.8 to 39.9)
    14.1 (0.00 to 38.1)
    23.5 (23.5 to 23.5)
    0.00 (0.00 to 0.00)
    0.00 (0.00 to 0.00)
    0.00 (0.00 to 0.00)
    0.00 (0.00 to 0.00)
    0.00 (0.00 to 0.00)
    0.00 (0.00 to 0.00)
    0.00 (0.00 to 0.00)
    0.00 (0.00 to 0.00)
    Notes
    [31] - N=0 for cycle 1, N=11 for cycle 2, N=0 for cycle 3, N=4 for cycle 4.
    [32] - N=0 for cycle 1, N=10 for cycle 2, N=0 for cycle 3, N=5 for cycle 4.
    [33] - N=0 for cycle 1, N=3 for cycle 2, N=0 for cycle 3, N=1 for cycle 4.
    [34] - N=33 for cycle 1, N=31 for cycle 2, N=22 for cycle 3, N=0 for cycle 4.
    [35] - N=35 for cycle 1, N=33 for cycle 2, N=28 for cycle 3, N=0 for cycle 4.
    [36] - N=30 for cycle 1, N=28 for cycle 2, N=20 for cycle 3, N=0 for cycle 4
    [37] - N=29 for cycle 1, N=28 for cycle 2, N=18 for cycle 3, N=0 for cycle 4.
    [38] - N=9 for cycle 1, N=9 for cycle 2, N=7 for cycle 3, N=0 for cycle 4.
    [39] - N=92 for cycle 1, N=63 for cycle 2, N=43 for cycle 3, N=0 for cycle 4.
    [40] - N=21 for cycle 1, N=13 for cycle 2, N=9 for cycle 3, N=0 for cycle 4.
    [41] - N=16 for cycle 1, N=12 for cycle 2, N=9 for cycle 3, N=0 for cycle 4.
    No statistical analyses for this end point

    Secondary: AUC of quavonlimab (MK-1308)

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    End point title
    		 AUC of quavonlimab (MK-1308)
    End point description
    AUC was defined as a measure of quavonlimab exposure that was calculated as the product of plasma drug concentration and time after drug administration. AUC determined by blood samples collected pre-dose and at designated timepoints post-dose are presented. The analysis population included all participants who complied with the protocol sufficiently to ensure that their data will be likely to show the effects of treatment, according to the underlying scientific model and had available data from at least 1 dose of study intervention. Per protocol, no analysis was planned for participants crossing over into MK-1308 25 mg and Pembrolizumab. AUC of quavonlimab is presented. N = number of participants analyzed per cycle.
    End point type
    Secondary
    End point timeframe
    At designated time points up to - Cohorts 1-3: Day 15 Cycle 3, Arms A, B, C, D, E: Day 15 Cycle 3, Arm F, G, I: Day 21 Cycle 3, Arm K: Day 21 Cycle 3. Each cycle is 21 days.
    End point values
    		 Cohort 1: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W Cohort 2: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W Cohort 3: MK-1308 200 mg Q3W + Pembro. 200 mg Q3W Arm A: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W Arm B: MK-1308 25 mg Q6W + Pembro. 200 mg Q3W Arm C: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W Arm D: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W Arm E: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W Arm F: MK-1308 25 mg Q6W + Pembro. 400 mg Q6W Co-admin Arm G: MK-1308 25 mg Q6W Arm I: MK-1308A Q6W (Co-form) Arm K: MK-1308A Q6W (Co-form)
    Number of subjects analysed
    14 [42]
    17 [43]
    8 [44]
    40 [45]
    40 [46]
    40 [47]
    40 [48]
    14 [49]
    111 [50]
    40 [51]
    29 [52]
    20 [53]
    Units: day*μg/mL
    geometric mean (geometric coefficient of variation)
        Cycle 1
    68.2 ( 17.7 )
    160 ( 19.5 )
    510 ( 25.7 )
    55.0 ( 26.6 )
    69.6 ( 33.5 )
    199 ( 36.2 )
    222 ( 39.7 )
    178 ( 17.6 )
    77.1 ( 32.7 )
    92.8 ( 38.1 )
    106 ( 34.7 )
    85.8 ( 24.2 )
        Cycle 2
    91.5 ( 19.9 )
    178 ( 53.9 )
    751 ( 23.4 )
    73.6 ( 26.4 )
    0.0 ( 0.0 )
    0.0 ( 0.0 )
    0.0 ( 0.0 )
    192 ( 17.7 )
    94.4 ( 43.9 )
    65.9 ( 27.8 )
    96.1 ( 39.7 )
    86.0 ( 47.7 )
        Cycle 3
    0.0 ( 0.0 )
    0.0 ( 0.0 )
    0.0 ( 0.0 )
    64.3 ( 56.5 )
    59.4 ( 74.9 )
    182 ( 75.1 )
    193 ( 90.8 )
    186 ( 22.1 )
    95.2 ( 63.4 )
    95.0 ( 58.2 )
    72.1 ( 9.92 )
    92.3 ( 60.2 )
    Notes
    [42] - N=10 for cycle 1, N=8 for cycle 2, N=0 for cycle 3.
    [43] - N=13 for cycle 1, N=4 for cycle 2, N=0 for cycle 3.
    [44] - N=8 for cycle 1, N=3 for cycle 2, N=0 for cycle 3.
    [45] - N=26 for cycle 1, N=21 for cycle 2, N=16 for cycle 3.
    [46] - N=21 for cycle 1, N=0 for cycle 2, N=20 for cycle 3.
    [47] - N=28 for cycle 1, N=0 for cycle 2, N=19 for cycle 3.
    [48] - N=28 for cycle 1, N=0 for cycle 2, N=16 for cycle 3.
    [49] - N=10 for cycle 1, N=8 for cycle 2, N=6 for cycle 3.
    [50] - N=34 for cycle 1, N=18 for cycle 2, N=17 for cycle 3.
    [51] - N=9 for cycle 1, N=4 for cycle 2, N=3 for cycle 3.
    [52] - N=8 for cycle 1, N=5 for cycle 2, N=2 for cycle 3.
    [53] - N=20 for cycle 1, N=14 for cycle 2, N=6 for cycle 3.
    No statistical analyses for this end point

    Secondary: Maximum concentration (Cmax) of quavonlimab

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    End point title
    		 Maximum concentration (Cmax) of quavonlimab
    End point description
    Cmax was defined as the maximum concentration of quavonlimab observed in plasma. Cmax determined by blood samples collected pre-dose and at designated timepoints post-dose are presented. The analysis population included all participants who complied with the protocol sufficiently to ensure that their data will be likely to show the effects of treatment, according to the underlying scientific model and had available data from at least 1 dose of study intervention. Per protocol, no analysis was planned for participants crossing over into MK-1308 25 mg and Pembrolizumab. Cmax of quavonlimab is presented. N = number of participants analyzed per cycle.
    End point type
    Secondary
    End point timeframe
    At designated time points up to - Cohorts 1-3: Day 15 Cycle 3, Arms A, B, C, D, E: Day 15 Cycle 3, Arm F, G, I: Day 21 Cycle 3, Arm K: Day 21 Cycle 3. Each cycle is 21 days.
    End point values
    		 Cohort 1: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W Cohort 2: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W Cohort 3: MK-1308 200 mg Q3W + Pembro. 200 mg Q3W Arm A: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W Arm B: MK-1308 25 mg Q6W + Pembro. 200 mg Q3W Arm C: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W Arm D: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W Arm E: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W Arm F: MK-1308 25 mg Q6W + Pembro. 400 mg Q6W Co-admin Arm G: MK-1308 25 mg Q6W Arm I: MK-1308A Q6W (Co-form) Arm K: MK-1308A Q6W (Co-form)
    Number of subjects analysed
    14 [54]
    17 [55]
    8 [56]
    40 [57]
    40 [58]
    40 [59]
    40 [60]
    14 [61]
    111 [62]
    40 [63]
    29 [64]
    20 [65]
    Units: μg/mL
    geometric mean (geometric coefficient of variation)
        Cycle 1
    8.23 ( 26.1 )
    22.5 ( 29.8 )
    68.3 ( 17.2 )
    7.28 ( 30.6 )
    8.02 ( 29.5 )
    23.4 ( 24.3 )
    24.1 ( 30.1 )
    25.0 ( 20.6 )
    7.25 ( 26.4 )
    7.42 ( 30.4 )
    8.06 ( 26.5 )
    8.23 ( 26.7 )
        Cycle 2
    9.41 ( 20.4 )
    23.5 ( 25.1 )
    71.9 ( 29.0 )
    8.58 ( 22.4 )
    0.0 ( 0.0 )
    0.0 ( 0.0 )
    0.0 ( 0.0 )
    26.3 ( 24.7 )
    7.65 ( 25.3 )
    7.22 ( 29.3 )
    8.17 ( 26.2 )
    7.99 ( 29.7 )
        Cycle 3
    9.11 ( 24.7 )
    23.3 ( 48.0 )
    88.3 ( 16.0 )
    7.72 ( 27.7 )
    6.98 ( 43.7 )
    22.7 ( 33.1 )
    24.2 ( 50.4 )
    27.2 ( 10.2 )
    7.94 ( 29.6 )
    6.65 ( 32.7 )
    7.25 ( 21.9 )
    7.94 ( 35.4 )
    Notes
    [54] - N=12 for cycle 1, N=13 for cycle 2, N=10 for cycle 3.
    [55] - N=17 for cycle 1, N=10 for cycle 2, N=9 for cycle 3.
    [56] - N=8 for cycle 1, N=7 for cycle 2, N=3 for cycle 3.
    [57] - N=38 for cycle 1, N=35 for cycle 2, N=31 for cycle 3.
    [58] - N=39 for cycle 1, N=0 for cycle 2, N=32 for cycle 3.
    [59] - N=38 for cycle 1, N=0 for cycle 2, N=26 for cycle 3.
    [60] - N=38 for cycle 1, N=0 for cycle 2, N=26 for cycle 3.
    [61] - N=14 for cycle 1, N=10 for cycle 2, N=7 for cycle 3.
    [62] - N=106 for cycle 1, N=95 for cycle 2, N=65 for cycle 3.
    [63] - N=37 for cycle 1, N=33 for cycle 2, N=11 for cycle 3.
    [64] - N=27 for cycle 1, N=21 for cycle 2, N=13 for cycle 3.
    [65] - N=20 for cycle 1, N=16 for cycle 2, N=12 for cycle 3.
    No statistical analyses for this end point

    Secondary: Minimum concentration (Cmin) of quavonlimab

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    End point title
    		 Minimum concentration (Cmin) of quavonlimab
    End point description
    Cmin was defined as the minimum or "trough" concentration of quavonlimab observed after its administration and just prior to the administration of a subsequent dose. Cmin determined by blood samples collected pre-dose and at designated timepoints post-dose are presented. The analysis population included all participants who complied with the protocol sufficiently to ensure that their data will be likely to show the effects of treatment, according to the underlying scientific model and had available data from at least 1 dose of study intervention. Per protocol, no analysis was planned for participants crossing over into MK-1308 25 mg and Pembrolizumab. Cmin of quavonlimab is presented. Data points listed as "0" had no participants that met per protocol criteria and were not analyzed. N = number of participants analyzed per cycle.
    End point type
    Secondary
    End point timeframe
    At designated time points up to - Cohorts 1-3: Day 15 Cycle 3, Arms A, B, C, D, E: Day 15 Cycle 3, Arm F, G, I: Day 21 Cycle 3, Arm K: Day 21 Cycle 3. Each cycle is 21 days.
    End point values
    		 Cohort 1: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W Cohort 2: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W Cohort 3: MK-1308 200 mg Q3W + Pembro. 200 mg Q3W Arm A: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W Arm B: MK-1308 25 mg Q6W + Pembro. 200 mg Q3W Arm C: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W Arm D: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W Arm E: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W Arm F: MK-1308 25 mg Q6W + Pembro. 400 mg Q6W Co-admin Arm G: MK-1308 25 mg Q6W Arm I: MK-1308A Q6W (Co-form) Arm K: MK-1308A Q6W (Co-form)
    Number of subjects analysed
    14 [66]
    17 [67]
    8 [68]
    40 [69]
    40 [70]
    40 [71]
    40 [72]
    14 [73]
    111 [74]
    40 [75]
    29 [76]
    20 [77]
    Units: μg/mL
    median (full range (min-max))
        Cycle 1
    1.44 (0.00 to 2.11)
    3.29 (0.00 to 6.86)
    8.01 (1.51 to 17.8)
    1.05 (0.00 to 1.80)
    0.00 (0.00 to 0.00)
    0.00 (0.00 to 3.44)
    15.6 (6.35 to 35.9)
    3.20 (0.00 to 5.26)
    0.00 (0.00 to 1.65)
    0.00 (0.00 to 1.26)
    0.00 (0.00 to 2.02)
    0.00 (0.00 to 1.32)
        Cycle 2
    1.75 (0.00 to 3.10)
    2.83 (0.00 to 10.3)
    17.4 (1.73 to 19.2)
    1.17 (0.00 to 2.73)
    0.00 (0.00 to 0.00)
    0.00 (0.00 to 0.00)
    25.2 (10.1 to 55.1)
    3.40 (1.35 to 6.32)
    0.00 (0.00 to 8.23)
    0.00 (0.00 to 2.09)
    0.00 (0.00 to 1.68)
    0.00 (0.00 to 1.65)
        Cycle 3
    0.00 (0.00 to 0.00)
    1.91 (1.91 to 1.91)
    0.00 (0.00 to 0.00)
    1.42 (0.00 to 2.86)
    0.00 (0.00 to 0.00)
    0.00 (0.00 to 3.10)
    29.3 (10.4 to 56.7)
    2.91 (2.21 to 5.77)
    0.00 (0.00 to 7.50)
    0.00 (0.00 to 7.20)
    0.00 (0.00 to 2.37)
    0.00 (0.00 to 1.05)
    Notes
    [66] - N=13 for cycle 1, N=11 for cycle 2, N=0 for cycle 3.
    [67] - N=14 for cycle 1, N=10 for cycle 2, N=1 for cycle 3.
    [68] - N=8 for cycle 1, N=3 for cycle 2, N=0 for cycle 3.
    [69] - N=35 for cycle 1, N=31 for cycle 2, N=22 for cycle 3.
    [70] - N=33 for cycle 1, N=0 for cycle 2, N=25 for cycle 3.
    [71] - N=26 for cycle 1, N=0 for cycle 2, N=21 for cycle 3.
    [72] - N=29 for cycle 1, N=28 for cycle 2, N=18 for cycle 3.
    [73] - N=10 for cycle 1, N=8 for cycle 2, N=6 for cycle 3.
    [74] - N=95 for cycle 1, N=62 for cycle 2, N=43 for cycle 3.
    [75] - N=32 for cycle 1, N=11 for cycle 2, N=8 for cycle 3.
    [76] - N=21 for cycle 1, N=13 for cycle 2, N=9 for cycle 3.
    [77] - N=16 for cycle 1, N=12 for cycle 2, N=9 for cycle 3.
    No statistical analyses for this end point

    Secondary: Number of participants with pembrolizumab anti-drug antibodies (ADAs)

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    End point title
    		 Number of participants with pembrolizumab anti-drug antibodies (ADAs) [78]
    End point description
    Non-Treatment emergent (TE) ADA refers to presence of ADAs (as determined by assay) in the absence of treatment with pembrolizumab (i.e., at predose). Evaluable participants (used as the denominator for analysis) are the total number of negative, inconclusive, and positive participants (non-treatment emergent, treatment emergent and treatment boosted). Inconclusive participants are the number of participants with no positive ADA samples present and the drug concentration in the last sample above the drug tolerance level. ADA determined by blood samples collected pre-dose and at designated timepoints post-dose are presented. The analysis population included all participants with at least one ADA sample available after treatment with pembrolizumab. Per protocol, no analysis was planned for arm G and participants crossing over into MK-1308 25 mg and Pembrolizumab. N = number of participants analyzed per cycle.
    End point type
    Secondary
    End point timeframe
    Cohorts 1-3: Predose and day 1 of cycles 2, 3, 5, 6, 7, 9 and every 4 cycles up to 35 cycles. Arms A-E: Predose and day 1 of cycles 1-5, 6, 8 and every 4 cycles up to 35 cycles. Arms F, I, K: Predose and day 1 of cycles 1, 2, 3, 4. Each cycle is 21 days.
    Notes
    [78] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Per protocol, no analysis was planned for arm G and participants crossing over into MK-1308 25 mg and Pembrolizumab.
    End point values
    		 Cohort 1: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W Cohort 2: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W Cohort 3: MK-1308 200 mg Q3W + Pembro. 200 mg Q3W Arm A: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W Arm B: MK-1308 25 mg Q6W + Pembro. 200 mg Q3W Arm C: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W Arm D: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W Arm E: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W Arm F: MK-1308 25 mg Q6W + Pembro. 400 mg Q6W Co-admin Arm I: MK-1308A Q6W (Co-form) Arm K: MK-1308A Q6W (Co-form)
    Number of subjects analysed
    12
    13
    5
    36
    39
    37
    35
    11
    103
    23
    20
    Units: Participants
    number (not applicable)
        Evaluable
    12
    13
    5
    36
    39
    37
    35
    11
    103
    23
    20
        Negative
    12
    12
    5
    31
    33
    33
    31
    10
    94
    20
    13
        Non - TE Neutralizing Antibody(NAB) NEG (Negative)
    0
    1
    0
    0
    0
    0
    0
    0
    0
    1
    0
        TE NAB NEG
    0
    0
    0
    4
    4
    3
    4
    1
    3
    0
    2
        TE NAB Positive (POS)
    0
    0
    0
    1
    0
    1
    0
    0
    0
    0
    1
        Inconclusive
    0
    0
    0
    0
    2
    0
    0
    0
    5
    2
    4
        Treatment Boosted (TB) NAB NEG
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    No statistical analyses for this end point

    Secondary: Number of participants with quavonlimab anti-drug antibodies (ADAs)

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    End point title
    		 Number of participants with quavonlimab anti-drug antibodies (ADAs)
    End point description
    Non-Treatment emergent (TE) ADA refers to presence of ADAs (as determined by assay) in the absence of treatment with quavonlimab (i.e., at predose). Evaluable participants (used as the denominator for analysis) are the total number of negative, inconclusive, and positive participants (non-treatment emergent, treatment emergent and treatment boosted). Inconclusive participants are the number of participants with no positive ADA samples present and the drug concentration in the last sample above the drug tolerance level. ADA determined by blood samples collected pre-dose and at designated timepoints post-dose are presented. The analysis population included all participants with at least one ADA sample available after treatment with quavonlimab. Per protocol, no analysis was planned for arm G and participants crossing over into MK-1308 25 mg and Pembrolizumab. N = number of participants analyzed per cycle.
    End point type
    Secondary
    End point timeframe
    Cohort 1-3: Predose and day 1 of cycles 2, 3, 5, 6, 7, 9 and every 4 cycles up to 35 cycles. Arms A-E: Predose and day 1 of cycle 1-5, 6, 8 and every 4 cycles up to 35 cycles. Arms F, G, I, K: Predose and day 1 of cycles 1, 2, 3, 4. Each cycle is 21 days.
    End point values
    		 Cohort 1: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W Cohort 2: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W Cohort 3: MK-1308 200 mg Q3W + Pembro. 200 mg Q3W Arm A: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W Arm B: MK-1308 25 mg Q6W + Pembro. 200 mg Q3W Arm C: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W Arm D: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W Arm E: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W Arm F: MK-1308 25 mg Q6W + Pembro. 400 mg Q6W Co-admin Arm G: MK-1308 25 mg Q6W Arm I: MK-1308A Q6W (Co-form) Arm K: MK-1308A Q6W (Co-form)
    Number of subjects analysed
    14
    15
    8
    36
    39
    37
    35
    11
    102
    38
    23
    20
    Units: Participants
    number (not applicable)
        Evaluable
    14
    15
    8
    36
    39
    37
    35
    11
    102
    38
    23
    20
        Negative
    3
    7
    4
    12
    6
    6
    8
    4
    35
    21
    8
    6
        Non - TE Neutralizing Antibody(NAB) NEG (Negative)
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
        TE NAB NEG
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
        TE NAB POS
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
        Inconclusive
    0
    0
    0
    0
    0
    0
    1
    0
    2
    1
    0
    1
        TB NAB NEG
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
        TB NAB MISSING
    0
    1
    0
    0
    0
    1
    0
    0
    3
    2
    0
    2
        TE NAB MISSING
    11
    7
    4
    23
    32
    30
    26
    7
    61
    13
    15
    11
        NON-TE NAB MISSING
    0
    0
    0
    1
    1
    0
    0
    0
    1
    1
    0
    0
    No statistical analyses for this end point

    Secondary: Dose Escalation, Dose Confirmation, Coformulation: ORR as assessed by investigator based on adjusted RECIST v1.1

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    End point title
    		 Dose Escalation, Dose Confirmation, Coformulation: ORR as assessed by investigator based on adjusted RECIST v1.1 [79]
    End point description
    ORR is defined as the percentage of participants with Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1). The percentage of participants who experience CR or PR as assessed by BICR will be presented. Per protocol, only data for Dose Escalation (Cohorts 1, 2, 3), Dose Confirmation (Arms A, B, C, D, E), Coformulation (Arms I and K) were presented for this endpoint, no analysis was planned for participants crossing over into MK-1308 25 mg and Pembrolizumab. Analysis population consists of all participants with a baseline scan that demonstrated measurable disease and who were administered at least 1 dose of study intervention.
    End point type
    Secondary
    End point timeframe
    Up to approximately 72 months
    Notes
    [79] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Per protocol, no analysis was planned for arm G and participants crossing over into MK-1308 25 mg and Pembrolizumab.
    End point values
    		 Cohort 1: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W Cohort 2: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W Cohort 3: MK-1308 200 mg Q3W + Pembro. 200 mg Q3W Arm A: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W Arm B: MK-1308 25 mg Q6W + Pembro. 200 mg Q3W Arm C: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W Arm D: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W Arm E: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W Arm I: MK-1308A Q6W (Co-form) Arm K: MK-1308A Q6W (Co-form)
    Number of subjects analysed
    14
    17
    8
    40
    40
    40
    40
    14
    29
    20
    Units: Percentage
        number (confidence interval 95%)
    0.0 (0.0 to 23.2)
    0.0 (0.0 to 19.5)
    25.0 (3.2 to 65.1)
    32.5 (18.6 to 49.1)
    37.5 (22.7 to 54.2)
    30.0 (16.6 to 46.5)
    15.0 (5.7 to 29.8)
    35.7 (12.8 to 64.9)
    10.3 (2.2 to 27.4)
    20.0 (5.7 to 43.7)
    No statistical analyses for this end point

    Secondary: Efficacy Expansion: Duration of Response (DOR) as assessed by BICR based on adjusted RECIST v1.1

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    End point title
    		 Efficacy Expansion: Duration of Response (DOR) as assessed by BICR based on adjusted RECIST v1.1 [80]
    End point description
    DOR was defined as the time from first documented evidence of complete response (CR: Disappearance of all target lesions) or confirmed partial response (PR: At least a 30% decrease in the sum of diameters of target lesions) until progressive disease (PD) or death. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. DOR as assessed by Blinded Independent Central Review (BICR) will be presented. A value of 9999 = median and lower limit not reached at time of data cut-off due to insufficient number of responding participants with relapse. Per protocol, only data for arms F and G were presented for this endpoint. Analysis population consists of all participants who received at least one dose of study intervention in arms F and G who had either a CR or PR.
    End point type
    Secondary
    End point timeframe
    Up to approximately 72 months
    Notes
    [80] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Per protocol, no analysis was planned for arm G and participants crossing over into MK-1308 25 mg and Pembrolizumab.
    End point values
    		 Arm F: MK-1308 25 mg Q6W + Pembro. 400 mg Q6W Co-admin Arm G: MK-1308 25 mg Q6W
    Number of subjects analysed
    15
    1
    Units: Months
        median (full range (min-max))
    9999 (6.2 to 9999)
    8.6 (8.6 to 8.6)
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Up to approximately 77 months
    Adverse event reporting additional description
    Analysis population for all-cause mortality consists of all allocated participants. Analysis population for safety consists of all participants who received at least one dose of study intervention.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    27.0
    Reporting groups
    Reporting group title
    Cohort 1: MK-1308 25 mg Q3W+Pembro. 200 mg Q3W
    Reporting group description
    		 -

    Reporting group title
    Cohort 3: MK-1308 200 mg Q3W + Pembro. 200 mg Q3W
    Reporting group description
    		 -

    Reporting group title
    Arm A: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W
    Reporting group description
    		 -

    Reporting group title
    Arm B: MK-1308 25 mg Q6W + Pembro. 200 mg Q3W
    Reporting group description
    		 -

    Reporting group title
    Arm C: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W
    Reporting group description
    		 -

    Reporting group title
    Cohort 2: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W
    Reporting group description
    		 -

    Reporting group title
    Arm D: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W
    Reporting group description
    		 -

    Reporting group title
    Arm E: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W
    Reporting group description
    		 -

    Reporting group title
    Arm F: MK-1308 25 mg Q6W + Pembro. 400 mg Q6W Co-admin
    Reporting group description
    		 -

    Reporting group title
    Arm F Crossover: MK-1308 25mg Q6W + Pembro. 400mg Q6W Co-admin
    Reporting group description
    		 -

    Reporting group title
    Arm G: MK-1308 25 mg Q6W
    Reporting group description
    		 -

    Reporting group title
    Arm I: MK-1308A Q6W (Co-form)
    Reporting group description
    		 -

    Reporting group title
    Arm K: MK-1308A Q6W (Co-form)
    Reporting group description
    		 -

    Serious adverse events
    		 Cohort 1: MK-1308 25 mg Q3W+Pembro. 200 mg Q3W Cohort 3: MK-1308 200 mg Q3W + Pembro. 200 mg Q3W Arm A: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W Arm B: MK-1308 25 mg Q6W + Pembro. 200 mg Q3W Arm C: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W Cohort 2: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W Arm D: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W Arm E: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W Arm F: MK-1308 25 mg Q6W + Pembro. 400 mg Q6W Co-admin Arm F Crossover: MK-1308 25mg Q6W + Pembro. 400mg Q6W Co-admin Arm G: MK-1308 25 mg Q6W Arm I: MK-1308A Q6W (Co-form) Arm K: MK-1308A Q6W (Co-form)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    2 / 14 (14.29%)
    4 / 8 (50.00%)
    20 / 40 (50.00%)
    14 / 40 (35.00%)
    23 / 40 (57.50%)
    10 / 17 (58.82%)
    16 / 40 (40.00%)
    10 / 14 (71.43%)
    31 / 111 (27.93%)
    4 / 21 (19.05%)
    9 / 40 (22.50%)
    15 / 29 (51.72%)
    4 / 20 (20.00%)
         number of deaths (all causes)
    13
    7
    33
    31
    32
    17
    35
    9
    86
    17
    16
    22
    15
         number of deaths resulting from adverse events
    0
    0
    3
    1
    7
    1
    3
    2
    3
    0
    0
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Bowen's disease
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    1 / 40 (2.50%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cancer pain
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    1 / 29 (3.45%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metastases to central nervous system
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    1 / 40 (2.50%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neuroendocrine tumour
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    1 / 111 (0.90%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Paraneoplastic syndrome
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    1 / 17 (5.88%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Prostate cancer
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    1 / 29 (3.45%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tumour pain
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    1 / 29 (3.45%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Deep vein thrombosis
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    1 / 111 (0.90%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Embolism
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    1 / 17 (5.88%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    1 / 40 (2.50%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    1 / 40 (2.50%)
    0 / 29 (0.00%)
    0 / 20 (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 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chest pain
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    1 / 111 (0.90%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Death
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    1 / 40 (2.50%)
    1 / 40 (2.50%)
    0 / 17 (0.00%)
    1 / 40 (2.50%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    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 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fatigue
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    1 / 17 (5.88%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    1 / 111 (0.90%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (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 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General physical health deterioration
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 8 (12.50%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Incarcerated hernia
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    1 / 111 (0.90%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Malaise
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    1 / 17 (5.88%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    1 / 40 (2.50%)
    1 / 40 (2.50%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    3 / 111 (2.70%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 3
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Multiple organ dysfunction syndrome
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    1 / 21 (4.76%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (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
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Benign prostatic hyperplasia
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    1 / 40 (2.50%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Atelectasis
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    1 / 40 (2.50%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (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
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    1 / 40 (2.50%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    2 / 40 (5.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    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
    0 / 0
    0 / 0
    Haemoptysis
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    1 / 40 (2.50%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    1 / 40 (2.50%)
    0 / 40 (0.00%)
    1 / 40 (2.50%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    1 / 21 (4.76%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lung disorder
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    1 / 111 (0.90%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    2 / 40 (5.00%)
    2 / 40 (5.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    1 / 40 (2.50%)
    1 / 29 (3.45%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 3
    1 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumothorax
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    1 / 40 (2.50%)
    2 / 40 (5.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonitis
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 8 (12.50%)
    5 / 40 (12.50%)
    4 / 40 (10.00%)
    2 / 40 (5.00%)
    0 / 17 (0.00%)
    2 / 40 (5.00%)
    0 / 14 (0.00%)
    1 / 111 (0.90%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    5 / 5
    4 / 4
    2 / 2
    0 / 0
    2 / 2
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    2 / 2
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    2 / 40 (5.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    1 / 111 (0.90%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    1 / 14 (7.14%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Confusional state
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    1 / 111 (0.90%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    Delirium
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    1 / 40 (2.50%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    1 / 29 (3.45%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    1 / 40 (2.50%)
    0 / 40 (0.00%)
    2 / 40 (5.00%)
    0 / 17 (0.00%)
    1 / 40 (2.50%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    2 / 2
    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
    0 / 0
    0 / 0
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    2 / 40 (5.00%)
    0 / 40 (0.00%)
    1 / 40 (2.50%)
    0 / 17 (0.00%)
    1 / 40 (2.50%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    1 / 20 (5.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    2 / 2
    0 / 0
    2 / 2
    0 / 0
    1 / 1
    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
    0 / 0
    0 / 0
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    1 / 40 (2.50%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (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
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Troponin increased
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    1 / 111 (0.90%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Animal bite
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    1 / 29 (3.45%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Radiation oesophagitis
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    1 / 40 (2.50%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (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
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Subdural haemorrhage
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    1 / 40 (2.50%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Acute myocardial infarction
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    1 / 40 (2.50%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    1 / 111 (0.90%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrioventricular block complete
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    1 / 40 (2.50%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (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
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac arrest
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    1 / 40 (2.50%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (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
    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
    0 / 0
    0 / 0
    Cardiac failure
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    1 / 40 (2.50%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (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
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure congestive
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    1 / 17 (5.88%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiogenic shock
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    1 / 40 (2.50%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         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 / 0
    0 / 0
    0 / 0
    0 / 0
    Coronary artery disease
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    1 / 14 (7.14%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    1 / 40 (2.50%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         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
    0 / 0
    0 / 0
    Tachyarrhythmia
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    1 / 40 (2.50%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (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
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pericarditis
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    1 / 40 (2.50%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (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
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Autonomic nervous system imbalance
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    1 / 17 (5.88%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Brain oedema
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    1 / 111 (0.90%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebral infarction
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    1 / 20 (5.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebral haematoma
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    1 / 111 (0.90%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    1 / 40 (2.50%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    1 / 40 (2.50%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Guillain-Barre syndrome
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    1 / 111 (0.90%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemorrhage intracranial
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    1 / 111 (0.90%)
    0 / 21 (0.00%)
    1 / 40 (2.50%)
    1 / 29 (3.45%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    1 / 29 (3.45%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolic encephalopathy
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    1 / 14 (7.14%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 8 (12.50%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    3 / 111 (2.70%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (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 / 3
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Autoimmune haemolytic anaemia
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    1 / 111 (0.90%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    Febrile neutropenia
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    1 / 14 (7.14%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    Mesenteric lymphadenitis
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    1 / 14 (7.14%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Vestibular disorder
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    1 / 111 (0.90%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Retinal detachment
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    1 / 40 (2.50%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    1 / 111 (0.90%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    1 / 20 (5.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 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
    0 / 0
    0 / 0
    Ascites
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 8 (12.50%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    1 / 40 (2.50%)
    0 / 29 (0.00%)
    0 / 20 (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 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    1 / 40 (2.50%)
    1 / 14 (7.14%)
    4 / 111 (3.60%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    1 / 29 (3.45%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 1
    4 / 4
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    1 / 40 (2.50%)
    0 / 40 (0.00%)
    1 / 40 (2.50%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    1 / 40 (2.50%)
    0 / 14 (0.00%)
    3 / 111 (2.70%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    2 / 3
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diverticular perforation
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    1 / 111 (0.90%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Enterocolitis
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    1 / 40 (2.50%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (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
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    1 / 111 (0.90%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Large intestinal obstruction
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    1 / 40 (2.50%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Large intestine perforation
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    1 / 17 (5.88%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    1 / 40 (2.50%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (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
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rectal haemorrhage
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    1 / 14 (7.14%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oesophagitis
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    1 / 40 (2.50%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    1 / 29 (3.45%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 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
    0 / 0
    0 / 0
    Subileus
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    1 / 21 (4.76%)
    1 / 40 (2.50%)
    0 / 29 (0.00%)
    0 / 20 (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 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    1 / 40 (2.50%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Autoimmune hepatitis
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    1 / 111 (0.90%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    Biliary obstruction
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    1 / 111 (0.90%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholangitis
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    1 / 29 (3.45%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholecystitis
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    1 / 111 (0.90%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    1 / 29 (3.45%)
    0 / 20 (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
    2 / 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
    0 / 0
    0 / 0
    Cholelithiasis
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    1 / 20 (5.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatitis
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    1 / 40 (2.50%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (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
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypertransaminasaemia
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    1 / 40 (2.50%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (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
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Immune-mediated hepatitis
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    1 / 40 (2.50%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    1 / 29 (3.45%)
    1 / 20 (5.00%)
         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
    1 / 1
    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
    0 / 0
    0 / 0
    Cholestasis
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    1 / 21 (4.76%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    1 / 40 (2.50%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (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
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin lesion
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    1 / 29 (3.45%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 8 (12.50%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    1 / 17 (5.88%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    2 / 111 (1.80%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    1 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haematuria
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nephritis
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    1 / 14 (7.14%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    Urinary tract obstruction
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinoma
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    1 / 14 (7.14%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Endocrine disorders
    Adrenal insufficiency
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    1 / 40 (2.50%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    1 / 14 (7.14%)
    2 / 111 (1.80%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    1 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyperthyroidism
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    1 / 40 (2.50%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (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
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypophysitis
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    1 / 40 (2.50%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    1 / 111 (0.90%)
    1 / 21 (4.76%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypothyroidism
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    1 / 40 (2.50%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (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
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthritis
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    1 / 40 (2.50%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (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
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Back pain
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    2 / 40 (5.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Muscular weakness
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    1 / 40 (2.50%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Osteolysis
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    1 / 14 (7.14%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spinal pain
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    1 / 111 (0.90%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spinal stenosis
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    1 / 40 (2.50%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (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
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Appendicitis perforated
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    1 / 111 (0.90%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arthritis infective
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    1 / 111 (0.90%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bacteraemia
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 8 (12.50%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    1 / 40 (2.50%)
    1 / 17 (5.88%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bronchopulmonary aspergillosis
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    1 / 40 (2.50%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    COVID-19 pneumonia
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    1 / 40 (2.50%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    1 / 111 (0.90%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Clostridium difficile infection
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    1 / 111 (0.90%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Encephalitis
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    2 / 40 (5.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    Herpes zoster
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    1 / 40 (2.50%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infective exacerbation of bronchiectasis
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    1 / 111 (0.90%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infective exacerbation of chronic obstructive airways disease
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    1 / 40 (2.50%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (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
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lower respiratory tract infection
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    1 / 29 (3.45%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Meningitis
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    1 / 40 (2.50%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    1 / 29 (3.45%)
    0 / 20 (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
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oesophageal candidiasis
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    1 / 40 (2.50%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         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
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    1 / 40 (2.50%)
    4 / 40 (10.00%)
    9 / 40 (22.50%)
    0 / 17 (0.00%)
    3 / 40 (7.50%)
    3 / 14 (21.43%)
    1 / 111 (0.90%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 4
    2 / 10
    0 / 0
    0 / 3
    0 / 3
    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 / 4
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    1 / 111 (0.90%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary sepsis
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    1 / 40 (2.50%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spinal cord infection
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    1 / 40 (2.50%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    1 / 17 (5.88%)
    1 / 40 (2.50%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    2 / 40 (5.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (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
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urosepsis
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    1 / 29 (3.45%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    1 / 111 (0.90%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diabetic metabolic decompensation
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    1 / 111 (0.90%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    Hypercalcaemia
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    1 / 29 (3.45%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyperglycaemia
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    1 / 17 (5.88%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    1 / 40 (2.50%)
    1 / 40 (2.50%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    1 / 29 (3.45%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyperkalaemia
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    1 / 17 (5.88%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Type 1 diabetes mellitus
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 8 (12.50%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    1 / 40 (2.50%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
    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
    0 / 0
    0 / 0
    Type 2 diabetes mellitus
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    1 / 40 (2.50%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    1 / 14 (7.14%)
    1 / 111 (0.90%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Cohort 1: MK-1308 25 mg Q3W+Pembro. 200 mg Q3W Cohort 3: MK-1308 200 mg Q3W + Pembro. 200 mg Q3W Arm A: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W Arm B: MK-1308 25 mg Q6W + Pembro. 200 mg Q3W Arm C: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W Cohort 2: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W Arm D: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W Arm E: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W Arm F: MK-1308 25 mg Q6W + Pembro. 400 mg Q6W Co-admin Arm F Crossover: MK-1308 25mg Q6W + Pembro. 400mg Q6W Co-admin Arm G: MK-1308 25 mg Q6W Arm I: MK-1308A Q6W (Co-form) Arm K: MK-1308A Q6W (Co-form)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    14 / 14 (100.00%)
    8 / 8 (100.00%)
    38 / 40 (95.00%)
    38 / 40 (95.00%)
    38 / 40 (95.00%)
    16 / 17 (94.12%)
    37 / 40 (92.50%)
    13 / 14 (92.86%)
    102 / 111 (91.89%)
    17 / 21 (80.95%)
    31 / 40 (77.50%)
    26 / 29 (89.66%)
    16 / 20 (80.00%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Seborrhoeic keratosis
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    1 / 17 (5.88%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    1 / 111 (0.90%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    1 / 29 (3.45%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    2
    0
    0
    1
    0
    Tumour pain
         subjects affected / exposed
    3 / 14 (21.43%)
    1 / 8 (12.50%)
    1 / 40 (2.50%)
    1 / 40 (2.50%)
    1 / 40 (2.50%)
    2 / 17 (11.76%)
    2 / 40 (5.00%)
    1 / 14 (7.14%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    1 / 40 (2.50%)
    1 / 29 (3.45%)
    0 / 20 (0.00%)
         occurrences all number
    3
    1
    1
    1
    1
    2
    2
    1
    0
    0
    1
    1
    0
    Tumour haemorrhage
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    2 / 21 (9.52%)
    1 / 40 (2.50%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    2
    1
    0
    0
    Vascular disorders
    Deep vein thrombosis
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    1 / 40 (2.50%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    1 / 14 (7.14%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Hypertension
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    1 / 40 (2.50%)
    0 / 40 (0.00%)
    1 / 17 (5.88%)
    1 / 40 (2.50%)
    0 / 14 (0.00%)
    5 / 111 (4.50%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    1 / 29 (3.45%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    1
    0
    5
    0
    0
    1
    0
    Hypotension
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 8 (0.00%)
    1 / 40 (2.50%)
    2 / 40 (5.00%)
    5 / 40 (12.50%)
    1 / 17 (5.88%)
    3 / 40 (7.50%)
    1 / 14 (7.14%)
    2 / 111 (1.80%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    2
    0
    1
    3
    5
    1
    4
    2
    2
    0
    0
    0
    0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    0 / 14 (0.00%)
    2 / 8 (25.00%)
    4 / 40 (10.00%)
    2 / 40 (5.00%)
    1 / 40 (2.50%)
    1 / 17 (5.88%)
    4 / 40 (10.00%)
    1 / 14 (7.14%)
    13 / 111 (11.71%)
    6 / 21 (28.57%)
    4 / 40 (10.00%)
    5 / 29 (17.24%)
    1 / 20 (5.00%)
         occurrences all number
    0
    2
    5
    2
    3
    1
    4
    1
    15
    6
    4
    5
    1
    Catheter site pain
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    1 / 40 (2.50%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    1 / 17 (5.88%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Chest discomfort
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    1 / 40 (2.50%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    1 / 111 (0.90%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    2 / 29 (6.90%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    1
    0
    0
    2
    0
    Chills
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    1 / 17 (5.88%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    1 / 111 (0.90%)
    0 / 21 (0.00%)
    1 / 40 (2.50%)
    2 / 29 (6.90%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    1
    0
    1
    3
    0
    Chest pain
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    2 / 40 (5.00%)
    3 / 40 (7.50%)
    2 / 40 (5.00%)
    1 / 17 (5.88%)
    1 / 40 (2.50%)
    0 / 14 (0.00%)
    3 / 111 (2.70%)
    3 / 21 (14.29%)
    0 / 40 (0.00%)
    2 / 29 (6.90%)
    1 / 20 (5.00%)
         occurrences all number
    0
    0
    2
    3
    2
    1
    1
    0
    3
    3
    0
    2
    1
    Early satiety
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    1 / 17 (5.88%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Fatigue
         subjects affected / exposed
    7 / 14 (50.00%)
    2 / 8 (25.00%)
    9 / 40 (22.50%)
    9 / 40 (22.50%)
    6 / 40 (15.00%)
    3 / 17 (17.65%)
    11 / 40 (27.50%)
    4 / 14 (28.57%)
    26 / 111 (23.42%)
    1 / 21 (4.76%)
    6 / 40 (15.00%)
    9 / 29 (31.03%)
    2 / 20 (10.00%)
         occurrences all number
    7
    2
    13
    12
    8
    3
    12
    5
    28
    1
    6
    9
    2
    General physical health deterioration
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    1 / 17 (5.88%)
    1 / 40 (2.50%)
    0 / 14 (0.00%)
    1 / 111 (0.90%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    1
    1
    0
    1
    0
    0
    0
    0
    Influenza like illness
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 8 (12.50%)
    1 / 40 (2.50%)
    2 / 40 (5.00%)
    2 / 40 (5.00%)
    1 / 17 (5.88%)
    2 / 40 (5.00%)
    0 / 14 (0.00%)
    2 / 111 (1.80%)
    0 / 21 (0.00%)
    1 / 40 (2.50%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    1
    1
    2
    3
    1
    2
    0
    2
    0
    1
    0
    0
    Localised oedema
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    1 / 17 (5.88%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    1 / 20 (5.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    1
    Malaise
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 8 (0.00%)
    1 / 40 (2.50%)
    1 / 40 (2.50%)
    1 / 40 (2.50%)
    0 / 17 (0.00%)
    1 / 40 (2.50%)
    2 / 14 (14.29%)
    0 / 111 (0.00%)
    1 / 21 (4.76%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    1
    1
    2
    0
    1
    2
    0
    1
    0
    0
    0
    Mucosal inflammation
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    1 / 40 (2.50%)
    1 / 17 (5.88%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    1 / 111 (0.90%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    1
    0
    0
    1
    0
    0
    0
    0
    Pyrexia
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 8 (0.00%)
    4 / 40 (10.00%)
    4 / 40 (10.00%)
    5 / 40 (12.50%)
    1 / 17 (5.88%)
    3 / 40 (7.50%)
    4 / 14 (28.57%)
    9 / 111 (8.11%)
    2 / 21 (9.52%)
    2 / 40 (5.00%)
    3 / 29 (10.34%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    4
    5
    10
    1
    3
    7
    12
    2
    3
    3
    0
    Oedema peripheral
         subjects affected / exposed
    0 / 14 (0.00%)
    2 / 8 (25.00%)
    0 / 40 (0.00%)
    5 / 40 (12.50%)
    1 / 40 (2.50%)
    1 / 17 (5.88%)
    1 / 40 (2.50%)
    1 / 14 (7.14%)
    8 / 111 (7.21%)
    0 / 21 (0.00%)
    1 / 40 (2.50%)
    0 / 29 (0.00%)
    1 / 20 (5.00%)
         occurrences all number
    0
    2
    0
    7
    1
    1
    1
    2
    12
    0
    1
    0
    1
    Immune system disorders
    Contrast media allergy
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    3 / 40 (7.50%)
    1 / 40 (2.50%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    1 / 29 (3.45%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    3
    1
    0
    0
    0
    0
    0
    0
    1
    0
    Drug hypersensitivity
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    1 / 111 (0.90%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Hypersensitivity
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    1 / 17 (5.88%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Reproductive system and breast disorders
    Gynaecomastia
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    1 / 17 (5.88%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    1 / 40 (2.50%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    1
    0
    0
    Vulvovaginal burning sensation
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 8 (12.50%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Chylothorax
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    1 / 17 (5.88%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Dysphonia
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    2 / 40 (5.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    1 / 14 (7.14%)
    3 / 111 (2.70%)
    0 / 21 (0.00%)
    1 / 40 (2.50%)
    1 / 29 (3.45%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    0
    0
    1
    3
    0
    1
    1
    0
    Cough
         subjects affected / exposed
    1 / 14 (7.14%)
    1 / 8 (12.50%)
    5 / 40 (12.50%)
    5 / 40 (12.50%)
    4 / 40 (10.00%)
    3 / 17 (17.65%)
    6 / 40 (15.00%)
    0 / 14 (0.00%)
    10 / 111 (9.01%)
    0 / 21 (0.00%)
    1 / 40 (2.50%)
    1 / 29 (3.45%)
    0 / 20 (0.00%)
         occurrences all number
    1
    1
    7
    5
    4
    3
    7
    0
    10
    0
    1
    1
    0
    Dyspnoea
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 8 (0.00%)
    7 / 40 (17.50%)
    7 / 40 (17.50%)
    7 / 40 (17.50%)
    3 / 17 (17.65%)
    5 / 40 (12.50%)
    2 / 14 (14.29%)
    9 / 111 (8.11%)
    0 / 21 (0.00%)
    1 / 40 (2.50%)
    1 / 29 (3.45%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    7
    9
    7
    3
    5
    2
    9
    0
    1
    1
    0
    Hypercapnia
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    1 / 14 (7.14%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Oropharyngeal pain
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    2 / 40 (5.00%)
    0 / 40 (0.00%)
    4 / 40 (10.00%)
    1 / 17 (5.88%)
    1 / 40 (2.50%)
    0 / 14 (0.00%)
    3 / 111 (2.70%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    1 / 29 (3.45%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    2
    0
    4
    1
    1
    0
    3
    0
    0
    1
    0
    Hypoxia
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    1 / 40 (2.50%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    1 / 14 (7.14%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    1
    0
    0
    0
    0
    0
    Pleural effusion
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 8 (0.00%)
    4 / 40 (10.00%)
    4 / 40 (10.00%)
    2 / 40 (5.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    1 / 111 (0.90%)
    0 / 21 (0.00%)
    1 / 40 (2.50%)
    1 / 29 (3.45%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    5
    4
    2
    0
    0
    0
    1
    0
    1
    1
    0
    Pneumonitis
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 8 (0.00%)
    1 / 40 (2.50%)
    6 / 40 (15.00%)
    3 / 40 (7.50%)
    0 / 17 (0.00%)
    4 / 40 (10.00%)
    1 / 14 (7.14%)
    1 / 111 (0.90%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    1 / 29 (3.45%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    1
    8
    4
    0
    5
    1
    1
    0
    0
    1
    0
    Productive cough
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    3 / 40 (7.50%)
    5 / 40 (12.50%)
    2 / 40 (5.00%)
    1 / 17 (5.88%)
    4 / 40 (10.00%)
    2 / 14 (14.29%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    3
    6
    2
    1
    5
    2
    0
    0
    0
    0
    0
    Wheezing
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    2 / 40 (5.00%)
    1 / 40 (2.50%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    3 / 40 (7.50%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    2 / 29 (6.90%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    2
    1
    0
    0
    3
    0
    0
    0
    0
    3
    0
    Psychiatric disorders
    Confusional state
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    1 / 17 (5.88%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    1 / 111 (0.90%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    2
    0
    0
    0
    0
    Insomnia
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    6 / 40 (15.00%)
    5 / 40 (12.50%)
    2 / 40 (5.00%)
    0 / 17 (0.00%)
    2 / 40 (5.00%)
    2 / 14 (14.29%)
    8 / 111 (7.21%)
    1 / 21 (4.76%)
    1 / 40 (2.50%)
    3 / 29 (10.34%)
    1 / 20 (5.00%)
         occurrences all number
    0
    0
    8
    5
    2
    0
    3
    3
    8
    1
    1
    3
    1
    Depression
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 8 (0.00%)
    2 / 40 (5.00%)
    1 / 40 (2.50%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    2 / 40 (5.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    1 / 29 (3.45%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    2
    1
    0
    0
    2
    0
    0
    0
    0
    1
    0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    10 / 40 (25.00%)
    5 / 40 (12.50%)
    9 / 40 (22.50%)
    1 / 17 (5.88%)
    5 / 40 (12.50%)
    6 / 14 (42.86%)
    10 / 111 (9.01%)
    1 / 21 (4.76%)
    1 / 40 (2.50%)
    2 / 29 (6.90%)
    3 / 20 (15.00%)
         occurrences all number
    0
    0
    12
    5
    11
    1
    7
    10
    13
    1
    1
    2
    4
    Ammonia increased
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    1 / 14 (7.14%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Aspartate aminotransferase increased
         subjects affected / exposed
    1 / 14 (7.14%)
    2 / 8 (25.00%)
    9 / 40 (22.50%)
    6 / 40 (15.00%)
    11 / 40 (27.50%)
    3 / 17 (17.65%)
    4 / 40 (10.00%)
    6 / 14 (42.86%)
    6 / 111 (5.41%)
    3 / 21 (14.29%)
    3 / 40 (7.50%)
    3 / 29 (10.34%)
    3 / 20 (15.00%)
         occurrences all number
    2
    2
    9
    6
    15
    4
    6
    12
    9
    3
    3
    4
    3
    Blood alkaline phosphatase increased
         subjects affected / exposed
    2 / 14 (14.29%)
    2 / 8 (25.00%)
    0 / 40 (0.00%)
    1 / 40 (2.50%)
    2 / 40 (5.00%)
    1 / 17 (5.88%)
    0 / 40 (0.00%)
    2 / 14 (14.29%)
    6 / 111 (5.41%)
    4 / 21 (19.05%)
    3 / 40 (7.50%)
    2 / 29 (6.90%)
    1 / 20 (5.00%)
         occurrences all number
    2
    2
    0
    1
    2
    1
    0
    2
    6
    5
    3
    4
    2
    Blood corticotrophin increased
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 8 (12.50%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    1 / 40 (2.50%)
    0 / 14 (0.00%)
    1 / 111 (0.90%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    1
    0
    1
    0
    0
    0
    0
    Blood bilirubin increased
         subjects affected / exposed
    0 / 14 (0.00%)
    2 / 8 (25.00%)
    0 / 40 (0.00%)
    1 / 40 (2.50%)
    0 / 40 (0.00%)
    1 / 17 (5.88%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    2 / 111 (1.80%)
    0 / 21 (0.00%)
    1 / 40 (2.50%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    2
    0
    4
    0
    1
    0
    0
    2
    0
    1
    0
    0
    Blood lactate dehydrogenase increased
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 8 (12.50%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    1 / 40 (2.50%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    3 / 111 (2.70%)
    1 / 21 (4.76%)
    1 / 40 (2.50%)
    1 / 29 (3.45%)
    0 / 20 (0.00%)
         occurrences all number
    0
    1
    0
    0
    1
    0
    0
    0
    4
    1
    1
    1
    0
    Blood creatinine increased
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 8 (12.50%)
    1 / 40 (2.50%)
    3 / 40 (7.50%)
    2 / 40 (5.00%)
    0 / 17 (0.00%)
    2 / 40 (5.00%)
    2 / 14 (14.29%)
    1 / 111 (0.90%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    1 / 29 (3.45%)
    2 / 20 (10.00%)
         occurrences all number
    0
    1
    1
    5
    4
    0
    4
    2
    1
    0
    0
    1
    2
    C-reactive protein increased
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    6 / 111 (5.41%)
    1 / 21 (4.76%)
    3 / 40 (7.50%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    7
    1
    3
    0
    0
    Cortisol increased
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 8 (12.50%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    2 / 14 (14.29%)
    2 / 8 (25.00%)
    1 / 40 (2.50%)
    1 / 40 (2.50%)
    1 / 40 (2.50%)
    1 / 17 (5.88%)
    3 / 40 (7.50%)
    1 / 14 (7.14%)
    4 / 111 (3.60%)
    3 / 21 (14.29%)
    4 / 40 (10.00%)
    3 / 29 (10.34%)
    1 / 20 (5.00%)
         occurrences all number
    2
    2
    1
    1
    2
    1
    3
    1
    4
    4
    4
    3
    1
    Lipase increased
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 8 (12.50%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    1 / 40 (2.50%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    3 / 111 (2.70%)
    3 / 21 (14.29%)
    2 / 40 (5.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    1
    0
    0
    1
    0
    0
    0
    3
    3
    2
    0
    0
    Lymphocyte count decreased
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 8 (12.50%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    1 / 17 (5.88%)
    1 / 40 (2.50%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    1
    1
    0
    0
    0
    0
    0
    0
    Neutrophil count decreased
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    1 / 40 (2.50%)
    2 / 40 (5.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    2 / 20 (10.00%)
         occurrences all number
    0
    0
    0
    1
    2
    0
    0
    0
    0
    0
    0
    0
    4
    Platelet count decreased
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 8 (12.50%)
    0 / 40 (0.00%)
    1 / 40 (2.50%)
    1 / 40 (2.50%)
    1 / 17 (5.88%)
    0 / 40 (0.00%)
    1 / 14 (7.14%)
    1 / 111 (0.90%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    1 / 20 (5.00%)
         occurrences all number
    0
    1
    0
    1
    1
    1
    0
    1
    1
    0
    0
    0
    1
    Weight decreased
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 8 (12.50%)
    5 / 40 (12.50%)
    4 / 40 (10.00%)
    3 / 40 (7.50%)
    3 / 17 (17.65%)
    7 / 40 (17.50%)
    4 / 14 (28.57%)
    6 / 111 (5.41%)
    2 / 21 (9.52%)
    0 / 40 (0.00%)
    1 / 29 (3.45%)
    1 / 20 (5.00%)
         occurrences all number
    0
    1
    5
    4
    3
    4
    7
    4
    6
    2
    0
    1
    1
    White blood cell count decreased
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 8 (12.50%)
    0 / 40 (0.00%)
    1 / 40 (2.50%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    3 / 20 (15.00%)
         occurrences all number
    0
    1
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    7
    Amylase increased
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    1 / 40 (2.50%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    1 / 111 (0.90%)
    2 / 21 (9.52%)
    2 / 40 (5.00%)
    1 / 29 (3.45%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    1
    2
    2
    1
    0
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    2 / 14 (14.29%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    2 / 40 (5.00%)
    1 / 14 (7.14%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    0
    2
    1
    0
    0
    0
    0
    0
    Dental restoration failure
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Animal bite
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Foot fracture
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Infusion related reaction
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 8 (12.50%)
    1 / 40 (2.50%)
    2 / 40 (5.00%)
    1 / 40 (2.50%)
    1 / 17 (5.88%)
    2 / 40 (5.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    1 / 29 (3.45%)
    0 / 20 (0.00%)
         occurrences all number
    0
    1
    1
    3
    2
    1
    2
    0
    0
    0
    0
    1
    0
    Cardiac disorders
    Tachycardia
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    1 / 14 (7.14%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Nervous system disorders
    Ataxia
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    1 / 17 (5.88%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Dysaesthesia
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Dizziness
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    5 / 40 (12.50%)
    1 / 40 (2.50%)
    1 / 40 (2.50%)
    0 / 17 (0.00%)
    5 / 40 (12.50%)
    2 / 14 (14.29%)
    7 / 111 (6.31%)
    2 / 21 (9.52%)
    1 / 40 (2.50%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    5
    1
    1
    0
    7
    2
    7
    2
    1
    0
    0
    Hypoaesthesia
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 8 (12.50%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    1 / 14 (7.14%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Headache
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 8 (0.00%)
    7 / 40 (17.50%)
    3 / 40 (7.50%)
    5 / 40 (12.50%)
    2 / 17 (11.76%)
    3 / 40 (7.50%)
    2 / 14 (14.29%)
    14 / 111 (12.61%)
    3 / 21 (14.29%)
    3 / 40 (7.50%)
    2 / 29 (6.90%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    7
    3
    5
    2
    3
    2
    15
    3
    4
    2
    0
    Neuralgia
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Neuropathy peripheral
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    3 / 40 (7.50%)
    1 / 40 (2.50%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    2 / 111 (1.80%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    4
    1
    0
    0
    0
    0
    2
    0
    0
    0
    0
    Presyncope
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    2 / 17 (11.76%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    1 / 111 (0.90%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    0
    0
    1
    0
    0
    0
    0
    Seizure
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    1 / 17 (5.88%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Somnolence
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    1 / 111 (0.90%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 14 (7.14%)
    2 / 8 (25.00%)
    1 / 40 (2.50%)
    3 / 40 (7.50%)
    8 / 40 (20.00%)
    2 / 17 (11.76%)
    5 / 40 (12.50%)
    2 / 14 (14.29%)
    11 / 111 (9.91%)
    4 / 21 (19.05%)
    8 / 40 (20.00%)
    3 / 29 (10.34%)
    5 / 20 (25.00%)
         occurrences all number
    2
    2
    1
    3
    9
    2
    5
    3
    12
    4
    9
    4
    13
    Eosinophilia
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    1 / 17 (5.88%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    1 / 111 (0.90%)
    2 / 21 (9.52%)
    3 / 40 (7.50%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    1
    2
    4
    0
    0
    Lymphopenia
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    3 / 111 (2.70%)
    3 / 21 (14.29%)
    3 / 40 (7.50%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    4
    4
    3
    0
    0
    Neutropenia
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 8 (12.50%)
    0 / 40 (0.00%)
    1 / 40 (2.50%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    1
    0
    2
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Thrombocytosis
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    2 / 21 (9.52%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    2
    0
    0
    0
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    1 / 17 (5.88%)
    2 / 40 (5.00%)
    0 / 14 (0.00%)
    1 / 111 (0.90%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    1
    2
    0
    1
    0
    0
    0
    0
    Eye disorders
    Lacrimation increased
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    1 / 17 (5.88%)
    0 / 40 (0.00%)
    1 / 14 (7.14%)
    1 / 111 (0.90%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    1
    1
    0
    0
    0
    0
    Vision blurred
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    1 / 29 (3.45%)
    2 / 20 (10.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    2
    Gastrointestinal disorders
    Abdominal distension
         subjects affected / exposed
    2 / 14 (14.29%)
    0 / 8 (0.00%)
    1 / 40 (2.50%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    1 / 17 (5.88%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    2 / 111 (1.80%)
    1 / 21 (4.76%)
    0 / 40 (0.00%)
    1 / 29 (3.45%)
    1 / 20 (5.00%)
         occurrences all number
    3
    0
    1
    0
    0
    1
    0
    0
    3
    1
    0
    1
    1
    Abdominal pain
         subjects affected / exposed
    2 / 14 (14.29%)
    1 / 8 (12.50%)
    2 / 40 (5.00%)
    1 / 40 (2.50%)
    1 / 40 (2.50%)
    1 / 17 (5.88%)
    2 / 40 (5.00%)
    1 / 14 (7.14%)
    13 / 111 (11.71%)
    1 / 21 (4.76%)
    3 / 40 (7.50%)
    1 / 29 (3.45%)
    2 / 20 (10.00%)
         occurrences all number
    2
    1
    2
    1
    1
    1
    2
    1
    13
    1
    3
    1
    2
    Abdominal pain upper
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 8 (12.50%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    4 / 40 (10.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    9 / 111 (8.11%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    2 / 29 (6.90%)
    0 / 20 (0.00%)
         occurrences all number
    0
    1
    0
    0
    4
    0
    0
    0
    9
    0
    0
    2
    0
    Aphthous ulcer
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Ascites
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    1 / 17 (5.88%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Colitis
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    1 / 40 (2.50%)
    1 / 14 (7.14%)
    2 / 111 (1.80%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    1
    2
    0
    0
    0
    0
    Constipation
         subjects affected / exposed
    3 / 14 (21.43%)
    1 / 8 (12.50%)
    4 / 40 (10.00%)
    4 / 40 (10.00%)
    5 / 40 (12.50%)
    3 / 17 (17.65%)
    4 / 40 (10.00%)
    3 / 14 (21.43%)
    14 / 111 (12.61%)
    2 / 21 (9.52%)
    4 / 40 (10.00%)
    4 / 29 (13.79%)
    2 / 20 (10.00%)
         occurrences all number
    4
    1
    4
    4
    5
    3
    4
    3
    17
    2
    4
    4
    2
    Dental caries
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Diarrhoea
         subjects affected / exposed
    3 / 14 (21.43%)
    3 / 8 (37.50%)
    9 / 40 (22.50%)
    3 / 40 (7.50%)
    9 / 40 (22.50%)
    2 / 17 (11.76%)
    10 / 40 (25.00%)
    3 / 14 (21.43%)
    27 / 111 (24.32%)
    4 / 21 (19.05%)
    3 / 40 (7.50%)
    2 / 29 (6.90%)
    3 / 20 (15.00%)
         occurrences all number
    4
    3
    18
    7
    15
    2
    22
    6
    37
    4
    3
    4
    3
    Diarrhoea haemorrhagic
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    1 / 14 (7.14%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Dry mouth
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 8 (12.50%)
    0 / 40 (0.00%)
    2 / 40 (5.00%)
    2 / 40 (5.00%)
    2 / 17 (11.76%)
    2 / 40 (5.00%)
    2 / 14 (14.29%)
    9 / 111 (8.11%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    1 / 29 (3.45%)
    1 / 20 (5.00%)
         occurrences all number
    0
    1
    0
    3
    2
    2
    2
    2
    9
    0
    0
    1
    1
    Dyspepsia
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    2 / 40 (5.00%)
    3 / 40 (7.50%)
    0 / 17 (0.00%)
    1 / 40 (2.50%)
    0 / 14 (0.00%)
    2 / 111 (1.80%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    2
    4
    0
    1
    0
    2
    0
    0
    0
    0
    Gingival pain
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    1 / 14 (7.14%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Haematochezia
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    1 / 111 (0.90%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Inguinal hernia
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    1 / 17 (5.88%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Nausea
         subjects affected / exposed
    1 / 14 (7.14%)
    3 / 8 (37.50%)
    10 / 40 (25.00%)
    5 / 40 (12.50%)
    2 / 40 (5.00%)
    0 / 17 (0.00%)
    10 / 40 (25.00%)
    0 / 14 (0.00%)
    21 / 111 (18.92%)
    0 / 21 (0.00%)
    4 / 40 (10.00%)
    1 / 29 (3.45%)
    0 / 20 (0.00%)
         occurrences all number
    1
    3
    17
    5
    3
    0
    16
    0
    24
    0
    4
    1
    0
    Obstruction gastric
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    1 / 17 (5.88%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Vomiting
         subjects affected / exposed
    2 / 14 (14.29%)
    2 / 8 (25.00%)
    5 / 40 (12.50%)
    4 / 40 (10.00%)
    3 / 40 (7.50%)
    5 / 17 (29.41%)
    6 / 40 (15.00%)
    0 / 14 (0.00%)
    4 / 111 (3.60%)
    1 / 21 (4.76%)
    2 / 40 (5.00%)
    1 / 29 (3.45%)
    0 / 20 (0.00%)
         occurrences all number
    4
    2
    9
    4
    3
    5
    6
    0
    4
    1
    2
    1
    0
    Small intestinal obstruction
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Hepatobiliary disorders
    Hepatitis
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    1 / 40 (2.50%)
    0 / 40 (0.00%)
    1 / 40 (2.50%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    1 / 14 (7.14%)
    2 / 111 (1.80%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    1
    0
    1
    0
    0
    1
    3
    0
    0
    0
    0
    Hypertransaminasaemia
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 8 (12.50%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    1 / 40 (2.50%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    1
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Immune-mediated hepatitis
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 8 (12.50%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    1 / 40 (2.50%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    1
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    1 / 40 (2.50%)
    0 / 40 (0.00%)
    1 / 40 (2.50%)
    1 / 17 (5.88%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    1
    0
    1
    1
    0
    0
    0
    0
    0
    0
    0
    Dry skin
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    1 / 40 (2.50%)
    2 / 40 (5.00%)
    0 / 17 (0.00%)
    2 / 40 (5.00%)
    1 / 14 (7.14%)
    4 / 111 (3.60%)
    0 / 21 (0.00%)
    1 / 40 (2.50%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    1
    2
    0
    2
    2
    4
    0
    1
    0
    0
    Erythema
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    1 / 17 (5.88%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    1 / 111 (0.90%)
    0 / 21 (0.00%)
    3 / 40 (7.50%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    1
    0
    3
    0
    0
    Night sweats
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    1 / 40 (2.50%)
    0 / 40 (0.00%)
    2 / 17 (11.76%)
    1 / 40 (2.50%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    1 / 40 (2.50%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    2
    1
    0
    0
    0
    1
    0
    0
    Rash maculo-papular
         subjects affected / exposed
    3 / 14 (21.43%)
    0 / 8 (0.00%)
    5 / 40 (12.50%)
    3 / 40 (7.50%)
    6 / 40 (15.00%)
    2 / 17 (11.76%)
    8 / 40 (20.00%)
    1 / 14 (7.14%)
    3 / 111 (2.70%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    1 / 29 (3.45%)
    0 / 20 (0.00%)
         occurrences all number
    4
    0
    5
    3
    10
    3
    8
    6
    4
    0
    0
    1
    0
    Rash
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 8 (12.50%)
    11 / 40 (27.50%)
    14 / 40 (35.00%)
    13 / 40 (32.50%)
    4 / 17 (23.53%)
    4 / 40 (10.00%)
    6 / 14 (42.86%)
    20 / 111 (18.02%)
    0 / 21 (0.00%)
    2 / 40 (5.00%)
    8 / 29 (27.59%)
    3 / 20 (15.00%)
         occurrences all number
    0
    1
    12
    16
    14
    6
    6
    7
    25
    0
    2
    8
    4
    Pruritus
         subjects affected / exposed
    2 / 14 (14.29%)
    0 / 8 (0.00%)
    12 / 40 (30.00%)
    10 / 40 (25.00%)
    11 / 40 (27.50%)
    6 / 17 (35.29%)
    15 / 40 (37.50%)
    5 / 14 (35.71%)
    38 / 111 (34.23%)
    2 / 21 (9.52%)
    9 / 40 (22.50%)
    11 / 29 (37.93%)
    8 / 20 (40.00%)
         occurrences all number
    3
    0
    15
    15
    12
    8
    20
    6
    42
    2
    9
    11
    10
    Rash papular
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    1 / 14 (7.14%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Rash pruritic
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    1 / 40 (2.50%)
    0 / 40 (0.00%)
    2 / 17 (11.76%)
    0 / 40 (0.00%)
    1 / 14 (7.14%)
    1 / 111 (0.90%)
    1 / 21 (4.76%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    3
    0
    1
    1
    1
    0
    0
    0
    Skin lesion
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    1 / 17 (5.88%)
    1 / 40 (2.50%)
    0 / 14 (0.00%)
    8 / 111 (7.21%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    1 / 29 (3.45%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    1
    0
    12
    0
    0
    1
    0
    Vitiligo
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    1 / 14 (7.14%)
    6 / 111 (5.41%)
    2 / 21 (9.52%)
    1 / 40 (2.50%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    7
    2
    1
    0
    0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    4 / 40 (10.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    0
    4
    0
    0
    0
    0
    0
    0
    0
    0
    Dysuria
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    1 / 40 (2.50%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    1 / 14 (7.14%)
    1 / 111 (0.90%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    1 / 29 (3.45%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    0
    0
    1
    0
    0
    1
    1
    0
    0
    1
    0
    Haematuria
         subjects affected / exposed
    2 / 14 (14.29%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    1 / 14 (7.14%)
    1 / 111 (0.90%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    2 / 20 (10.00%)
         occurrences all number
    2
    0
    0
    0
    0
    0
    0
    1
    1
    0
    0
    0
    3
    Hydronephrosis
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 8 (12.50%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Nephrolithiasis
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 8 (12.50%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Pollakiuria
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    1 / 40 (2.50%)
    1 / 40 (2.50%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    0
    1
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Renal colic
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Urinary tract pain
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    1 / 14 (7.14%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Urinary tract inflammation
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Endocrine disorders
    Adrenal insufficiency
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    3 / 40 (7.50%)
    4 / 40 (10.00%)
    4 / 40 (10.00%)
    1 / 17 (5.88%)
    1 / 40 (2.50%)
    0 / 14 (0.00%)
    1 / 111 (0.90%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    3
    4
    4
    1
    1
    0
    1
    0
    0
    0
    0
    Hyperthyroidism
         subjects affected / exposed
    3 / 14 (21.43%)
    3 / 8 (37.50%)
    4 / 40 (10.00%)
    3 / 40 (7.50%)
    2 / 40 (5.00%)
    1 / 17 (5.88%)
    7 / 40 (17.50%)
    1 / 14 (7.14%)
    3 / 111 (2.70%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    3
    3
    4
    3
    2
    1
    7
    1
    3
    0
    0
    0
    0
    Hypophysitis
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    1 / 40 (2.50%)
    1 / 40 (2.50%)
    1 / 40 (2.50%)
    0 / 17 (0.00%)
    1 / 40 (2.50%)
    1 / 14 (7.14%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    1 / 40 (2.50%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    1
    1
    1
    0
    1
    1
    0
    0
    1
    0
    0
    Hypothyroidism
         subjects affected / exposed
    3 / 14 (21.43%)
    0 / 8 (0.00%)
    5 / 40 (12.50%)
    9 / 40 (22.50%)
    8 / 40 (20.00%)
    3 / 17 (17.65%)
    8 / 40 (20.00%)
    1 / 14 (7.14%)
    3 / 111 (2.70%)
    1 / 21 (4.76%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    3 / 20 (15.00%)
         occurrences all number
    3
    0
    5
    9
    8
    3
    8
    1
    3
    1
    0
    0
    4
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    2 / 14 (14.29%)
    1 / 8 (12.50%)
    4 / 40 (10.00%)
    6 / 40 (15.00%)
    7 / 40 (17.50%)
    2 / 17 (11.76%)
    4 / 40 (10.00%)
    1 / 14 (7.14%)
    14 / 111 (12.61%)
    3 / 21 (14.29%)
    3 / 40 (7.50%)
    1 / 29 (3.45%)
    1 / 20 (5.00%)
         occurrences all number
    3
    2
    4
    11
    11
    2
    4
    1
    17
    3
    4
    1
    1
    Back pain
         subjects affected / exposed
    3 / 14 (21.43%)
    1 / 8 (12.50%)
    1 / 40 (2.50%)
    2 / 40 (5.00%)
    1 / 40 (2.50%)
    1 / 17 (5.88%)
    4 / 40 (10.00%)
    2 / 14 (14.29%)
    9 / 111 (8.11%)
    3 / 21 (14.29%)
    1 / 40 (2.50%)
    1 / 29 (3.45%)
    1 / 20 (5.00%)
         occurrences all number
    3
    1
    1
    2
    2
    1
    4
    2
    9
    3
    1
    1
    1
    Joint range of motion decreased
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Muscular weakness
         subjects affected / exposed
    1 / 14 (7.14%)
    1 / 8 (12.50%)
    1 / 40 (2.50%)
    2 / 40 (5.00%)
    1 / 40 (2.50%)
    0 / 17 (0.00%)
    3 / 40 (7.50%)
    0 / 14 (0.00%)
    1 / 111 (0.90%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    1
    1
    1
    2
    2
    0
    3
    0
    1
    0
    0
    0
    0
    Muscle rigidity
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    1 / 14 (7.14%)
    1 / 111 (0.90%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    1
    0
    0
    0
    0
    Joint swelling
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    1 / 40 (2.50%)
    1 / 14 (7.14%)
    1 / 111 (0.90%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    1
    1
    0
    0
    0
    0
    Musculoskeletal chest pain
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    1 / 40 (2.50%)
    2 / 40 (5.00%)
    2 / 40 (5.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    1 / 111 (0.90%)
    1 / 21 (4.76%)
    0 / 40 (0.00%)
    2 / 29 (6.90%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    1
    2
    2
    0
    0
    0
    4
    1
    0
    3
    0
    Musculoskeletal pain
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    2 / 40 (5.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    1 / 40 (2.50%)
    0 / 14 (0.00%)
    3 / 111 (2.70%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    0
    2
    0
    0
    2
    0
    3
    0
    0
    0
    0
    Myalgia
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 8 (0.00%)
    2 / 40 (5.00%)
    1 / 40 (2.50%)
    5 / 40 (12.50%)
    1 / 17 (5.88%)
    2 / 40 (5.00%)
    0 / 14 (0.00%)
    4 / 111 (3.60%)
    2 / 21 (9.52%)
    2 / 40 (5.00%)
    1 / 29 (3.45%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    2
    1
    6
    1
    2
    0
    4
    3
    2
    1
    0
    Pain in extremity
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 8 (0.00%)
    2 / 40 (5.00%)
    0 / 40 (0.00%)
    1 / 40 (2.50%)
    0 / 17 (0.00%)
    2 / 40 (5.00%)
    1 / 14 (7.14%)
    9 / 111 (8.11%)
    2 / 21 (9.52%)
    2 / 40 (5.00%)
    1 / 29 (3.45%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    2
    0
    1
    0
    2
    2
    9
    2
    2
    1
    0
    Synovial cyst
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 8 (12.50%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Infections and infestations
    Cellulitis
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 8 (12.50%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    1 / 111 (0.90%)
    0 / 21 (0.00%)
    1 / 40 (2.50%)
    1 / 29 (3.45%)
    0 / 20 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    1
    0
    1
    1
    0
    Conjunctivitis
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 8 (12.50%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    1 / 111 (0.90%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Cystitis
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    1 / 40 (2.50%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Gingivitis
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    1 / 40 (2.50%)
    0 / 40 (0.00%)
    1 / 17 (5.88%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Infection
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    1 / 14 (7.14%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Herpes zoster
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    1 / 40 (2.50%)
    1 / 40 (2.50%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    1 / 111 (0.90%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    1 / 29 (3.45%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    0
    1
    1
    0
    0
    0
    1
    0
    0
    1
    0
    Nasopharyngitis
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 8 (12.50%)
    0 / 40 (0.00%)
    1 / 40 (2.50%)
    2 / 40 (5.00%)
    0 / 17 (0.00%)
    1 / 40 (2.50%)
    0 / 14 (0.00%)
    1 / 111 (0.90%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    1
    0
    1
    3
    0
    1
    0
    1
    0
    0
    0
    0
    Oral candidiasis
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    1 / 40 (2.50%)
    1 / 17 (5.88%)
    1 / 40 (2.50%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    1
    0
    0
    0
    0
    0
    0
    Sinusitis
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    1 / 40 (2.50%)
    0 / 40 (0.00%)
    1 / 40 (2.50%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    1 / 14 (7.14%)
    1 / 111 (0.90%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    2 / 29 (6.90%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    1
    0
    1
    0
    0
    1
    1
    0
    0
    2
    0
    Pneumonia
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    3 / 40 (7.50%)
    1 / 40 (2.50%)
    0 / 17 (0.00%)
    1 / 40 (2.50%)
    0 / 14 (0.00%)
    2 / 111 (1.80%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    1 / 29 (3.45%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    5
    2
    0
    1
    0
    2
    0
    0
    1
    0
    Oral herpes
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    1 / 17 (5.88%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    2 / 111 (1.80%)
    0 / 21 (0.00%)
    1 / 40 (2.50%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    2
    0
    1
    0
    0
    Tinea infection
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    1 / 14 (7.14%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 8 (12.50%)
    2 / 40 (5.00%)
    5 / 40 (12.50%)
    5 / 40 (12.50%)
    1 / 17 (5.88%)
    5 / 40 (12.50%)
    0 / 14 (0.00%)
    3 / 111 (2.70%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    3 / 20 (15.00%)
         occurrences all number
    0
    1
    2
    5
    7
    1
    6
    0
    4
    0
    0
    0
    3
    Urinary tract infection
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    3 / 40 (7.50%)
    2 / 40 (5.00%)
    0 / 17 (0.00%)
    3 / 40 (7.50%)
    0 / 14 (0.00%)
    7 / 111 (6.31%)
    0 / 21 (0.00%)
    1 / 40 (2.50%)
    2 / 29 (6.90%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    7
    8
    0
    3
    0
    8
    0
    1
    2
    0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    5 / 14 (35.71%)
    3 / 8 (37.50%)
    13 / 40 (32.50%)
    12 / 40 (30.00%)
    8 / 40 (20.00%)
    3 / 17 (17.65%)
    7 / 40 (17.50%)
    1 / 14 (7.14%)
    18 / 111 (16.22%)
    2 / 21 (9.52%)
    2 / 40 (5.00%)
    2 / 29 (6.90%)
    2 / 20 (10.00%)
         occurrences all number
    5
    3
    15
    13
    10
    3
    8
    2
    19
    2
    2
    3
    2
    Dehydration
         subjects affected / exposed
    1 / 14 (7.14%)
    1 / 8 (12.50%)
    4 / 40 (10.00%)
    2 / 40 (5.00%)
    1 / 40 (2.50%)
    1 / 17 (5.88%)
    3 / 40 (7.50%)
    1 / 14 (7.14%)
    1 / 111 (0.90%)
    0 / 21 (0.00%)
    1 / 40 (2.50%)
    1 / 29 (3.45%)
    0 / 20 (0.00%)
         occurrences all number
    1
    1
    10
    2
    1
    1
    4
    2
    1
    0
    1
    1
    0
    Glucose tolerance impaired
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 8 (12.50%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Hypercalcaemia
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    3 / 40 (7.50%)
    1 / 40 (2.50%)
    1 / 40 (2.50%)
    0 / 17 (0.00%)
    1 / 40 (2.50%)
    0 / 14 (0.00%)
    3 / 111 (2.70%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    4
    3
    2
    0
    1
    0
    3
    0
    0
    0
    0
    Hyperkalaemia
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    2 / 40 (5.00%)
    4 / 40 (10.00%)
    5 / 40 (12.50%)
    0 / 17 (0.00%)
    1 / 40 (2.50%)
    3 / 14 (21.43%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    2
    5
    7
    0
    1
    4
    0
    0
    0
    0
    0
    Hyperglycaemia
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    1 / 40 (2.50%)
    7 / 40 (17.50%)
    1 / 40 (2.50%)
    0 / 17 (0.00%)
    2 / 40 (5.00%)
    4 / 14 (28.57%)
    5 / 111 (4.50%)
    1 / 21 (4.76%)
    3 / 40 (7.50%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    1
    8
    1
    0
    2
    9
    5
    1
    4
    0
    0
    Hyperuricaemia
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    1 / 40 (2.50%)
    3 / 40 (7.50%)
    0 / 17 (0.00%)
    1 / 40 (2.50%)
    2 / 14 (14.29%)
    2 / 111 (1.80%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    1 / 20 (5.00%)
         occurrences all number
    0
    0
    0
    1
    3
    0
    1
    2
    2
    0
    0
    0
    2
    Hypocalcaemia
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    2 / 40 (5.00%)
    0 / 40 (0.00%)
    1 / 40 (2.50%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    2 / 14 (14.29%)
    2 / 111 (1.80%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    3
    0
    1
    0
    0
    2
    2
    0
    0
    0
    0
    Hypoalbuminaemia
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 8 (12.50%)
    2 / 40 (5.00%)
    2 / 40 (5.00%)
    2 / 40 (5.00%)
    0 / 17 (0.00%)
    1 / 40 (2.50%)
    2 / 14 (14.29%)
    6 / 111 (5.41%)
    1 / 21 (4.76%)
    0 / 40 (0.00%)
    1 / 29 (3.45%)
    3 / 20 (15.00%)
         occurrences all number
    0
    1
    3
    2
    2
    0
    1
    2
    6
    1
    0
    1
    8
    Hypoglycaemia
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    1 / 40 (2.50%)
    1 / 40 (2.50%)
    1 / 40 (2.50%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    1 / 14 (7.14%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    1 / 20 (5.00%)
         occurrences all number
    0
    0
    2
    1
    1
    0
    0
    3
    0
    0
    0
    0
    1
    Hypokalaemia
         subjects affected / exposed
    1 / 14 (7.14%)
    2 / 8 (25.00%)
    4 / 40 (10.00%)
    2 / 40 (5.00%)
    1 / 40 (2.50%)
    2 / 17 (11.76%)
    5 / 40 (12.50%)
    2 / 14 (14.29%)
    5 / 111 (4.50%)
    1 / 21 (4.76%)
    1 / 40 (2.50%)
    0 / 29 (0.00%)
    4 / 20 (20.00%)
         occurrences all number
    1
    3
    5
    2
    1
    2
    10
    5
    5
    1
    1
    0
    8
    Hypomagnesaemia
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 8 (12.50%)
    2 / 40 (5.00%)
    2 / 40 (5.00%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    4 / 40 (10.00%)
    2 / 14 (14.29%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    2 / 29 (6.90%)
    0 / 20 (0.00%)
         occurrences all number
    0
    1
    2
    3
    0
    0
    4
    3
    0
    0
    0
    3
    0
    Hyponatraemia
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 8 (12.50%)
    2 / 40 (5.00%)
    2 / 40 (5.00%)
    2 / 40 (5.00%)
    2 / 17 (11.76%)
    2 / 40 (5.00%)
    1 / 14 (7.14%)
    2 / 111 (1.80%)
    1 / 21 (4.76%)
    1 / 40 (2.50%)
    0 / 29 (0.00%)
    1 / 20 (5.00%)
         occurrences all number
    0
    2
    2
    2
    4
    2
    3
    1
    2
    1
    1
    0
    1
    Hypophagia
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 8 (12.50%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    1 / 40 (2.50%)
    0 / 17 (0.00%)
    0 / 40 (0.00%)
    0 / 14 (0.00%)
    0 / 111 (0.00%)
    0 / 21 (0.00%)
    0 / 40 (0.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    1
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Hypophosphataemia
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 8 (0.00%)
    1 / 40 (2.50%)
    1 / 40 (2.50%)
    0 / 40 (0.00%)
    0 / 17 (0.00%)
    3 / 40 (7.50%)
    1 / 14 (7.14%)
    2 / 111 (1.80%)
    0 / 21 (0.00%)
    2 / 40 (5.00%)
    0 / 29 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    2
    2
    0
    0
    5
    1
    2
    0
    2
    0
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    28 Aug 2017
    AM 01: Amendment developed due to requirement by regulatory authorities around safety monitoring of Japan specific participants in the MK-1308-001 clinical trial.
    04 Jan 2018
    AM 02: The protocol was amended to add additional exploratory biomarker, safety assessments, and exclusion criteria.
    20 Apr 2018
    AM 03: The protocol was amended to explore an additional dose escalation cohort and dose confirmation arm, to modify the dose limiting toxicity (DLT) reporting period for dose confirmation, to clarify pre-treatment requirements for brain metastases, and to modify the futility analysis.
    30 Apr 2019
    AM 04: The protocol was amended to add an efficacy expansion phase in melanoma and to improve overall protocol clarity and consistency as well as to correct typographical errors identified post publishing.
    07 May 2019
    AM 05: The protocol was amended to add new interim analysis safety and efficacy data that supports the recommended Phase 2 dose (RP2D) used in the melanoma expansion arm.
    25 Dec 2019
    AM 06: This amendment added Process 2 material and incorporated Food and Drug Administration (FDA) feedback on Amendment 05.
    18 Mar 2020
    AM 07: This amendment added a cohort (Arm I) to evaluate a coformulated product of MK-1308 + pembrolizumab (MK-1308A).
    18 Nov 2020
    AM 08: This amendment added additional cohorts to evaluate a coformulated product of MK 1308 + pembrolizumab (MK-1308A) in the global study as well as in China-and Japan specific Arms: - Arm J - participants with programmed cell death protein 1/Ligand 1 (PD-1/L1) refractory melanoma in specific countries. - Arm K - Chinese participants who reside in China with a diagnosis of any relapsed or refractory solid tumor. Arm K is open to sites in mainland China only. - Arm L - Japanese participants who reside in Japan with a diagnosis of Stage IV non–small cell lung cancer (NSCLC). Arm L is open to sites in Japan only. Collection of pre-and on-treatment tumor biopsies from participants in Arms F, G, and J was added.
    30 Jul 2021
    AM 09: The protocol was amended to update the dose modification and toxicity management guidelines for immune-related adverse event (irAEs), to remove Arm L (Japan) from the study, to clarify pharmacokinetics (PK) collection timings, to align with the biomarker plan, and to remove Translational Oncology Research from the study.
    24 Jan 2022
    AM 10: The protocol was amended to remove Arm J from the study.
    09 Dec 2022
    AM 11: Merck Sharp & Dohme Corp. underwent an entity name and address change to Merck Sharp & Dohme LLC, Rahway, NJ, USA. This conversion resulted only in an entity name change and update to the address.
    01 Mar 2023
    AM 12: Merck Sharp & Dohme Corp. underwent an entity name and address change to Merck Sharp & Dohme LLC, Rahway, NJ, USA. This conversion resulted only in an entity name change and update to the address.

    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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