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FRACTION-Lung: An Investigational Immuno-therapy Study to Test Combination Treatments in Patients With Advanced Non-Small Cell Lung Cancer

Sponsor
Bristol-Myers Squibb (Industry)
Overall Status
Terminated
CT.gov ID
NCT02750514
Collaborator
(none)
295
Enrollment
50
Locations
5
Arms
44.7
Actual Duration (Months)
5.9
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether Nivolumab, in combination with other therapies, is effective in patients with advanced Non-Small Cell lung cancer

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
295 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 2, Fast Real Time Assessment of Combination Therapies in Immuno-Oncology Study in Subjects With Advanced Non-Small Cell Lung Cancer (FRACTION-Lung)
Actual Study Start Date :
May 9, 2016
Actual Primary Completion Date :
Jan 29, 2020
Actual Study Completion Date :
Jan 29, 2020

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Nivolumab

Nivolumab Monotherapy - Arm associated with this intervention is closed. Nivolumab is no longer given as an active comparator

Biological: Nivolumab
Arm associated with this intervention is closed. Nivolumab is no longer given as an active comparator.
Other Names:
  • BMS-936558
  • MDX-1106
  • OPDIVO

    		•
    Experimental: Nivolumab & Dasatinib

    Nivolumab in combination with Dasatinib

    Biological: Nivolumab
    Arm associated with this intervention is closed. Nivolumab is no longer given as an active comparator.
    Other Names:
  • BMS-936558
  • MDX-1106
  • OPDIVO

    • Drug: Dasatinib
    Other Names:
  • BMS-354825
  • SPRYCEL

    		•
    Experimental: Nivolumab & Relatlimab

    Nivolumab in combination with Relatlimab

    Biological: Nivolumab
    Arm associated with this intervention is closed. Nivolumab is no longer given as an active comparator.
    Other Names:
  • BMS-936558
  • MDX-1106
  • OPDIVO

    • Biological: Relatlimab
    Other Names:
  • BMS-986016

    		•
    Experimental: Nivolumab & Ipilimumab

    Nivolumab in combination with Ipilimumab

    Biological: Nivolumab
    Arm associated with this intervention is closed. Nivolumab is no longer given as an active comparator.
    Other Names:
  • BMS-936558
  • MDX-1106
  • OPDIVO

    • Biological: Ipilimumab
    Other Names:
  • BMS-734016
  • Yervoy

    		•
    Experimental: Nivolumab & BMS-986205

    Nivolumab in combination with BMS- 986205

    Biological: Nivolumab
    Arm associated with this intervention is closed. Nivolumab is no longer given as an active comparator.
    Other Names:
  • BMS-936558
  • MDX-1106
  • OPDIVO

    • Drug: BMS-986205
    Specified dose on specified days

    Outcome Measures

    Primary Outcome Measures

    1. Objective Response Rate (ORR) [From first dose to 2 years following last dose (up to 30 months)]

      ORR is defined as the percentage of participants whose confirmed best overall response (BOR) is either a complete response (CR) or partial response (PR). BOR was assessed by investigator per RECIST1.1. Results are presented by study track. Track 1 = participants naive for prior immuno-oncology (IO) therapy and PD-L1 positive Track 2 = participants naive for prior immuno-oncology (IO) therapy and PD-L1 negative Track 3 = participants with prior anti-PD-1/PD-L1 therapy Track 4 = participants naive for prior anti-PD-1/PD-L1 therapy (established upon enrollment closure of tracks 1,2 and 3) Track 5 = participants with prior anti-PD-1/PD-L1 therapy (established upon enrollment closure of tracks 1,2 and 3). Results for each study track are presented only for treatment groups who received a treatment in that specific track.

    2. Duration of Response (DOR) [From first dose to 2 years following last dose (up to 30 months)]

      DOR, computed for all treated participants with a confirmed BOR of CR or PR, is defined as the time between the date of first response and the date of first documented disease progression (as determined by RECIST 1.1) or death due to any cause. Results are presented by study track. Track 1 = participants naive for prior immuno-oncology (IO) therapy and PD-L1 positive Track 2 = participants naive for prior immuno-oncology (IO) therapy and PD-L1 negative Track 3 = participants with prior anti-PD-1/PD-L1 therapy Track 4 = participants naive for prior anti-PD-1/PD-L1 therapy (established upon enrollment closure of tracks 1,2 and 3) Track 5 = participants with prior anti-PD-1/PD-L1 therapy (established upon enrollment closure of tracks 1,2 and 3). Results for each study track are presented only for treatment groups who received a treatment in that specific track.

    3. Progression Free Survival Rate (PFSR) at 24 Weeks [From first dose to 24 weeks after first dose]

      The PFSR at 24 weeks is defined as the proportion of treated participants remaining progression free and surviving at 24 weeks since the first dosing date. Results are presented by study track. Track 1 = participants naive for prior immuno-oncology (IO) therapy and PD-L1 positive (>=1%) Track 2 = participants naive for prior immuno-oncology (IO) therapy and PD-L1 negative (<1%) Track 3 = participants with prior anti-PD-1/PD-L1 therapy Track 4 = participants naive for prior anti-PD-1/PD-L1 therapy (established upon enrollment closure of tracks 1,2 and 3) Track 5 = participants with prior anti-PD-1/PD-L1 therapy (established upon enrollment closure of tracks 1,2 and 3). Results for each study track are presented only for treatment groups who received a treatment in that specific track.

    Secondary Outcome Measures

    1. Percentage of Participants Experiencing Adverse Events (AEs) [From first dose to 100 days following last dose]

      This outcome measure describes the percentage of participants who experienced any grade, all causality AEs during the specified time frame

    2. Percentage of Participants Experiencing Serious Adverse Events (SAEs) [From first dose to 100 days following last dose]

      This outcome measure describes the percentage of participants who experienced any grade, all causality SAEs during the specified time frame

    3. Percentage of Participants Experiencing Adverse Events (AEs) Leading to Discontinuation [From first dose to 100 days following last dose]

      This outcome measure describes the percentage of participants who experienced all causality AEs leading to discontinuation of study therapy during the specified time frame

    4. Percentage of Participants Experiencing Death [From first dose to up to 45 months following first dose]

      This outcome measure describes the percentage of participants who died (due to any cause) during the specified time frame

    5. Number of Participants Experiencing Laboratory Abnormalities in Hepatic Tests [From first dose to 100 days following last dose (approximately 9 months)]

      The following measurements will be considered laboratory abnormalities for hepatic tests: ALT or AST > 3 x ULN, > 5 x ULN, > 10 x ULN and > 20 x ULN Total bilirubin > 2 x ULN Concurrent (within 1 day) ALT or AST > 3 x ULN and total bilirubin > 2 x ULN Concurrent (within 30 days) ALT or AST > 3 x ULN and total bilirubin > 2 x ULN ALT=Alanine aminotransferase AST=Aspartate aminotransferase ULN=Upper Limit of Normal

    6. Number of Participants Experiencing Laboratory Abnormalities in Thyroid Tests [From first dose to 100 days following last dose (approximately 9 months)]

      The following measurements will be considered laboratory abnormalities for thyroid tests: TSH value > ULN and With baseline TSH value ≤ ULN At least one T3/T4 test value < LLN Low TSH < LLN and With baseline TSH value ≥ LLN At least one T3/T4 test value > ULN TSH = thyroid stimulating hormone ULN=Upper Limit of Normal LLN=Lower Limit of Normal T3=Triiodothyronine T4=Thyroxine

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No

    For more information regarding Bristol-Myers Squibb Clinical Trial participation, please visit www.BMSStudyConnect.com

    Inclusion Criteria:

    • Advanced Non Small Cell Lung Cancer (NSCLC)

    • Eastern Cooperative Oncology Group (ECOG) Performance status of ≤ 1

    • Life expectancy of at least 3 months from most recent chemotherapy or immunotherapy treatment

    • Must have at least 1 lesion with measurable disease

    Exclusion Criteria:

    • Subjects with certain mutations that have not been treated with a targeted therapy prior to enrollment

    • Subjects who need daily oxygen therapy

    • People with autoimmune disease

    Other protocol defined inclusion/exclusion criteria could apply

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 City of Hope National Medical Center Duarte California United States 91010
    2 University of Southern California (USC) Los Angeles California United States 90033
    3 Cedars-Sinai Medical Center Los Angeles California United States 90048
    4 University of Californa, Los Angeles (UCLA) Los Angeles California United States 90095
    5 Hoag Memorial Hospital Presbyterian Newport Beach California United States 92658
    6 University of California San Diego San Diego California United States 92122
    7 University of Colorado Denver Aurora Colorado United States 80045
    8 Yale Cancer Center New Haven Connecticut United States 06511
    9 University of Kansas Cancer Center Westwood Kansas United States 66205
    10 University of Maryland - Marlene and Stewart Greenebaum Cancer Center Baltimore Maryland United States 21201
    11 Sidney Kimmel Comprehensive Cancer Center Baltimore Maryland United States 21287
    12 Massachusetts General Hospital Boston Massachusetts United States 02114
    13 Beth Israel Deaconess Medical Center Boston Massachusetts United States 02215
    14 Dana Farber/Harvard Cancer Center Boston Massachusetts United States 02215
    15 University of Michigan Health System (UMHS) - University Hospital (University of Michigan Medical Ce Ann Arbor Michigan United States 48109
    16 Karmanos Cancer Institute Detroit Michigan United States 48201
    17 Washington University, The Center for Advanced Medicine Saint Louis Missouri United States 63110
    18 Comprehensive Cancer Centers of Nevada Las Vegas Nevada United States 89119
    19 Roswell Park Cancer Institute Buffalo New York United States 14263
    20 Memorial Sloan Kettering Cancer Center New York New York United States 10065
    21 Univ of NC Shool of Medicine Chapel Hill North Carolina United States 27514
    22 The Ohio State University Columbus Ohio United States 43210
    23 Northwest Cancer Specialists Portland Oregon United States 97225
    24 Thomas Jefferson University Philadelphia Pennsylvania United States 19107
    25 Fox Chase Cancer Center Philadelphia Pennsylvania United States 19111-2497
    26 University of Pittsburgh Medical Center Pittsburgh Pennsylvania United States 15217
    27 The West Clinic, P.C. d/b/a West Cancer Center Germantown Tennessee United States 38138
    28 Sarah Cannon Cancer Center Nashville Tennessee United States 37203
    29 Sammons Cancer Center (Uso) Dallas Texas United States 75246
    30 Texas Oncology, P.A. Fort Worth Texas United States 76104
    31 The University of Texas MD Anderson Cancer Center Houston Texas United States 77030
    32 Us Oncology Tyler Texas United States 75702
    33 Huntsman Cancer Institute Salt Lake City Utah United States 84112
    34 Virginia Cancer Specialists, PC Fairfax Virginia United States 22031
    35 University of Washington-Seattle Cancer Care Alliance Seattle Washington United States 98109
    36 Local Institution Clayton Victoria Australia
    37 Local Institution Salzburg Austria 5020
    38 Juravinski Cancer Centre, Hamilton Health Sciences-Mcmaster Univeristy's Faculty Of Health Sciences Hamilton Ontario Canada L8V 5C2
    39 University Of Ottawa - The Ottawa Hospital Cancer centre Ottawa Ontario Canada K1H 8L6
    40 Local Institution Edmonton Canada T6G 1Z2
    41 Local Institution Paris France 75005
    42 Local Institution Toulouse France 31059
    43 Local Institution Villejuif Cedex France 94805
    44 Local Institution Milano Italy 20132
    45 Local Institution Milan Italy 20141
    46 Local Institution Rozzano Italy 20089
    47 Local Institution Madrid Spain 28041
    48 Local Institution Madrid Spain 28050
    49 Local Institution Pamplona Spain 31008
    50 Local Institution Lausanne Switzerland CH-1011

    Sponsors and Collaborators

    • Bristol-Myers Squibb

    Investigators

    • Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

    Study Documents (Full-Text)

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Bristol-Myers Squibb
    ClinicalTrials.gov Identifier:
    NCT02750514
    Other Study ID Numbers:
    • CA018-001
    First Posted:
    Apr 25, 2016
    Last Update Posted:
    Mar 22, 2021
    Last Verified:
    Feb 1, 2021
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Carcinoma, Non-Small-Cell Lung
    Nivolumab
    Ipilimumab
    Dasatinib
    Linrodostat

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail The total number of participants randomized and treated is 295. Each participant was assigned to 1 of 5 non-consecutive Tracks (based on previous therapy exposure and/or PD-1/PD-L1 expression). 14 of the 295 participants, after receiving initial treatment, were re-randomized to a second, different treatment (either under a different Track or within the same Track).
    Arm/Group Title Nivolumab Nivolumab + Dasatinib Nivolumab + BMS986016 Nivolumab + Ipilimumab Nivolumab + BMS986205
    Arm/Group Description Nivolumab monotherapy 240 mg Q2W administered until completion of 6 cycles (1 cycle=4 weeks) Nivolumab 240 mg Q2W + Dasatinib 100 mg QD, administered until completion of 6 cycles (1 cycle=4 weeks) Nivolumab 240 mg Q2W + BMS986016 20 mg Q2W, administered until completion of 6 cycles (1 cycle=4 weeks) Nivolumab 240 mg Q2W for 12 doses + Ipilimumab 1 mg/kg Q6W for 4 doses, administered until completion of 24 weeks of study Nivolumab 480 mg Q4W + BMS986205 100 mg QD, administered until completion of 6 cycles (1 cycle=4 weeks)
    Period Title: Track 1
    STARTED 40 4 0 3 0
    COMPLETED 13 2 0 1 0
    NOT COMPLETED 27 2 0 2 0
    Period Title: Track 1
    STARTED 9 8 2 12 0
    COMPLETED 3 0 0 5 0
    NOT COMPLETED 6 8 2 7 0
    Period Title: Track 1
    STARTED 0 41 16 18 0
    COMPLETED 0 5 1 2 0
    NOT COMPLETED 0 36 15 16 0
    Period Title: Track 1
    STARTED 0 53 0 60 0
    COMPLETED 0 2 0 18 0
    NOT COMPLETED 0 51 0 42 0
    Period Title: Track 1
    STARTED 0 0 0 0 43
    COMPLETED 0 0 0 0 0
    NOT COMPLETED 0 0 0 0 43

    Baseline Characteristics

    Arm/Group Title Nivolumab Nivolumab + Dasatinib Nivolumab + BMS986016 Nivolumab + Ipilimumab Nivolumab + BMS986205 Total
    Arm/Group Description Nivolumab monotherapy 240 mg Q2W administered until completion of 6 cycles (1 cycle=4 weeks) Nivolumab 240 mg Q2W + Dasatinib 100 mg QD, administered until completion of 6 cycles (1 cycle=4 weeks) Nivolumab 240 mg Q2W + BMS986016 20 mg Q2W, administered until completion of 6 cycles (1 cycle=4 weeks) Nivolumab 240 mg Q2W for 12 doses + Ipilimumab 1 mg/kg Q6W for 4 doses, administered until completion of 24 weeks of study Nivolumab 480 mg Q4W + BMS986205 100 mg QD, administered until completion of 6 cycles (1 cycle=4 weeks) Total of all reporting groups
    Overall Participants 49 104 17 88 37 295
    Age (Years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Years]
    64.5
    (10.27)
    63.6
    (9.25)
    66.6
    (9.17)
    62.3
    (9.04)
    63.6
    (7.89)
    63.5
    (9.21)
    Sex: Female, Male (Count of Participants)
    Female
    21
    42.9%
    34
    32.7%
    8
    47.1%
    38
    43.2%
    21
    56.8%
    122
    41.4%
    Male
    28
    57.1%
    70
    67.3%
    9
    52.9%
    50
    56.8%
    16
    43.2%
    173
    58.6%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    1
    2%
    2
    1.9%
    0
    0%
    5
    5.7%
    1
    2.7%
    9
    3.1%
    Not Hispanic or Latino
    25
    51%
    65
    62.5%
    17
    100%
    58
    65.9%
    27
    73%
    192
    65.1%
    Unknown or Not Reported
    23
    46.9%
    37
    35.6%
    0
    0%
    25
    28.4%
    9
    24.3%
    94
    31.9%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Asian
    2
    4.1%
    7
    6.7%
    2
    11.8%
    2
    2.3%
    3
    8.1%
    16
    5.4%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    0
    0%
    6
    5.8%
    1
    5.9%
    6
    6.8%
    6
    16.2%
    19
    6.4%
    White
    42
    85.7%
    85
    81.7%
    14
    82.4%
    78
    88.6%
    26
    70.3%
    245
    83.1%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    5
    10.2%
    6
    5.8%
    0
    0%
    2
    2.3%
    2
    5.4%
    15
    5.1%

    Outcome Measures

    1. Primary Outcome
    Title Objective Response Rate (ORR)
    Description ORR is defined as the percentage of participants whose confirmed best overall response (BOR) is either a complete response (CR) or partial response (PR). BOR was assessed by investigator per RECIST1.1. Results are presented by study track. Track 1 = participants naive for prior immuno-oncology (IO) therapy and PD-L1 positive Track 2 = participants naive for prior immuno-oncology (IO) therapy and PD-L1 negative Track 3 = participants with prior anti-PD-1/PD-L1 therapy Track 4 = participants naive for prior anti-PD-1/PD-L1 therapy (established upon enrollment closure of tracks 1,2 and 3) Track 5 = participants with prior anti-PD-1/PD-L1 therapy (established upon enrollment closure of tracks 1,2 and 3). Results for each study track are presented only for treatment groups who received a treatment in that specific track.
    Time Frame From first dose to 2 years following last dose (up to 30 months)

    Outcome Measure Data

    Analysis Population Description
    All treated participants. 14 participants, after receiving initial treatment, were re-randomized to a second, different treatment. They were analyzed under both groups they received treatment for.
    Arm/Group Title Nivolumab Nivolumab + Dasatinib Nivolumab + BMS986016 Nivolumab + Ipilimumab Nivolumab + BMS986205
    Arm/Group Description Nivolumab monotherapy 240 mg Q2W administered until completion of 6 cycles (1 cycle=4 weeks) Nivolumab 240 mg Q2W + Dasatinib 100 mg QD, administered until completion of 6 cycles (1 cycle=4 weeks) Nivolumab 240 mg Q2W + BMS986016 20 mg Q2W, administered until completion of 6 cycles (1 cycle=4 weeks) Nivolumab 240 mg Q2W for 12 doses + Ipilimumab 1 mg/kg Q6W for 4 doses, administered until completion of 24 weeks of study Nivolumab 480 mg Q4W + BMS986205 100 mg QD, administered until completion of 6 cycles (1 cycle=4 weeks)
    Measure Participants 49 106 18 93 43
    Study Track 1
    17.5
    35.7%
    25.0
    24%
    0
    0%
    Study Track 2
    0
    0%
    0
    0%
    0
    0%
    25.0
    28.4%
    Study Track 3
    2.4
    4.9%
    0
    0%
    5.6
    32.9%
    Study Track 4
    1.9
    3.9%
    20.0
    19.2%
    Study Track 5
    2.3
    4.7%
    2. Primary Outcome
    Title Duration of Response (DOR)
    Description DOR, computed for all treated participants with a confirmed BOR of CR or PR, is defined as the time between the date of first response and the date of first documented disease progression (as determined by RECIST 1.1) or death due to any cause. Results are presented by study track. Track 1 = participants naive for prior immuno-oncology (IO) therapy and PD-L1 positive Track 2 = participants naive for prior immuno-oncology (IO) therapy and PD-L1 negative Track 3 = participants with prior anti-PD-1/PD-L1 therapy Track 4 = participants naive for prior anti-PD-1/PD-L1 therapy (established upon enrollment closure of tracks 1,2 and 3) Track 5 = participants with prior anti-PD-1/PD-L1 therapy (established upon enrollment closure of tracks 1,2 and 3). Results for each study track are presented only for treatment groups who received a treatment in that specific track.
    Time Frame From first dose to 2 years following last dose (up to 30 months)

    Outcome Measure Data

    Analysis Population Description
    All participants with a confirmed best overall response (BOR) of Complete Response (CR) or Partial Response (PR).
    Arm/Group Title Nivolumab Nivolumab + Dasatinib Nivolumab + BMS986016 Nivolumab + Ipilimumab Nivolumab + BMS986205
    Arm/Group Description Nivolumab monotherapy 240 mg Q2W administered until completion of 6 cycles (1 cycle=4 weeks) Nivolumab 240 mg Q2W + Dasatinib 100 mg QD, administered until completion of 6 cycles (1 cycle=4 weeks) Nivolumab 240 mg Q2W + BMS986016 20 mg Q2W, administered until completion of 6 cycles (1 cycle=4 weeks) Nivolumab 240 mg Q2W for 12 doses + Ipilimumab 1 mg/kg Q6W for 4 doses, administered until completion of 24 weeks of study Nivolumab 480 mg Q4W + BMS986205 100 mg QD, administered until completion of 6 cycles (1 cycle=4 weeks)
    Measure Participants 7 3 0 16 1
    Study Track 1
    12.81
    8.57
    Study Track 2
    NA
    Study Track 3
    NA
    NA
    Study Track 4
    NA
    12.65
    Study Track 5
    3.75
    3. Primary Outcome
    Title Progression Free Survival Rate (PFSR) at 24 Weeks
    Description The PFSR at 24 weeks is defined as the proportion of treated participants remaining progression free and surviving at 24 weeks since the first dosing date. Results are presented by study track. Track 1 = participants naive for prior immuno-oncology (IO) therapy and PD-L1 positive (>=1%) Track 2 = participants naive for prior immuno-oncology (IO) therapy and PD-L1 negative (<1%) Track 3 = participants with prior anti-PD-1/PD-L1 therapy Track 4 = participants naive for prior anti-PD-1/PD-L1 therapy (established upon enrollment closure of tracks 1,2 and 3) Track 5 = participants with prior anti-PD-1/PD-L1 therapy (established upon enrollment closure of tracks 1,2 and 3). Results for each study track are presented only for treatment groups who received a treatment in that specific track.
    Time Frame From first dose to 24 weeks after first dose

    Outcome Measure Data

    Analysis Population Description
    All treated participants. 14 participants, after receiving initial treatment, were re-randomized to a second, different treatment. They were analyzed under both groups they received treatment for.
    Arm/Group Title Nivolumab Nivolumab + Dasatinib Nivolumab + BMS986016 Nivolumab + Ipilimumab Nivolumab + BMS986205
    Arm/Group Description Nivolumab monotherapy 240 mg Q2W administered until completion of 6 cycles (1 cycle=4 weeks) Nivolumab 240 mg Q2W + Dasatinib 100 mg QD, administered until completion of 6 cycles (1 cycle=4 weeks) Nivolumab 240 mg Q2W + BMS986016 20 mg Q2W, administered until completion of 6 cycles (1 cycle=4 weeks) Nivolumab 240 mg Q2W for 12 doses + Ipilimumab 1 mg/kg Q6W for 4 doses, administered until completion of 24 weeks of study Nivolumab 480 mg Q4W + BMS986205 100 mg QD, administered until completion of 6 cycles (1 cycle=4 weeks)
    Measure Participants 49 106 18 93 43
    Study Track 1
    0.302
    0.6%
    NA
    NaN
    NA
    NaN
    Study Track 2
    NA
    NaN
    NA
    NaN
    NA
    NaN
    0.455
    0.5%
    Study Track 3
    0.191
    0.4%
    NA
    NaN
    NA
    NaN
    Study Track 4
    NA
    NaN
    0.391
    0.4%
    Study Track 5
    0.111
    0.2%
    4. Secondary Outcome
    Title Percentage of Participants Experiencing Adverse Events (AEs)
    Description This outcome measure describes the percentage of participants who experienced any grade, all causality AEs during the specified time frame
    Time Frame From first dose to 100 days following last dose

    Outcome Measure Data

    Analysis Population Description
    All treated participants. 14 participants, after receiving initial treatment, were re-randomized to a second, different treatment. They were analyzed under both groups they received treatment for.
    Arm/Group Title Nivolumab Nivolumab + Dasatinib Nivolumab + BMS986016 Nivolumab + Ipilimumab Nivolumab + BMS986205
    Arm/Group Description Nivolumab monotherapy 240 mg Q2W administered until completion of 6 cycles (1 cycle=4 weeks) Nivolumab 240 mg Q2W + Dasatinib 100 mg QD, administered until completion of 6 cycles (1 cycle=4 weeks) Nivolumab 240 mg Q2W + BMS986016 20 mg Q2W, administered until completion of 6 cycles (1 cycle=4 weeks) Nivolumab 240 mg Q2W for 12 doses + Ipilimumab 1 mg/kg Q6W for 4 doses, administered until completion of 24 weeks of study Nivolumab 480 mg Q4W + BMS986205 100 mg QD, administered until completion of 6 cycles (1 cycle=4 weeks)
    Measure Participants 49 106 18 93 43
    Number [Percent of Participants]
    100.0
    204.1%
    100.0
    96.2%
    100.0
    588.2%
    98.9
    112.4%
    100.0
    270.3%
    5. Secondary Outcome
    Title Percentage of Participants Experiencing Serious Adverse Events (SAEs)
    Description This outcome measure describes the percentage of participants who experienced any grade, all causality SAEs during the specified time frame
    Time Frame From first dose to 100 days following last dose

    Outcome Measure Data

    Analysis Population Description
    All treated participants. 14 participants, after receiving initial treatment, were re-randomized to a second, different treatment. They were analyzed under both groups they received treatment for.
    Arm/Group Title Nivolumab Nivolumab + Dasatinib Nivolumab + BMS986016 Nivolumab + Ipilimumab Nivolumab + BMS986205
    Arm/Group Description Nivolumab monotherapy 240 mg Q2W administered until completion of 6 cycles (1 cycle=4 weeks) Nivolumab 240 mg Q2W + Dasatinib 100 mg QD, administered until completion of 6 cycles (1 cycle=4 weeks) Nivolumab 240 mg Q2W + BMS986016 20 mg Q2W, administered until completion of 6 cycles (1 cycle=4 weeks) Nivolumab 240 mg Q2W for 12 doses + Ipilimumab 1 mg/kg Q6W for 4 doses, administered until completion of 24 weeks of study Nivolumab 480 mg Q4W + BMS986205 100 mg QD, administered until completion of 6 cycles (1 cycle=4 weeks)
    Measure Participants 49 106 18 93 43
    Number [Percent of Participants]
    57.1
    116.5%
    53.8
    51.7%
    61.1
    359.4%
    58.1
    66%
    60.5
    163.5%
    6. Secondary Outcome
    Title Percentage of Participants Experiencing Adverse Events (AEs) Leading to Discontinuation
    Description This outcome measure describes the percentage of participants who experienced all causality AEs leading to discontinuation of study therapy during the specified time frame
    Time Frame From first dose to 100 days following last dose

    Outcome Measure Data

    Analysis Population Description
    All treated participants. 14 participants, after receiving initial treatment, were re-randomized to a second, different treatment. They were analyzed under both groups they received treatment for.
    Arm/Group Title Nivolumab Nivolumab + Dasatinib Nivolumab + BMS986016 Nivolumab + Ipilimumab Nivolumab + BMS986205
    Arm/Group Description Nivolumab monotherapy 240 mg Q2W administered until completion of 6 cycles (1 cycle=4 weeks) Nivolumab 240 mg Q2W + Dasatinib 100 mg QD, administered until completion of 6 cycles (1 cycle=4 weeks) Nivolumab 240 mg Q2W + BMS986016 20 mg Q2W, administered until completion of 6 cycles (1 cycle=4 weeks) Nivolumab 240 mg Q2W for 12 doses + Ipilimumab 1 mg/kg Q6W for 4 doses, administered until completion of 24 weeks of study Nivolumab 480 mg Q4W + BMS986205 100 mg QD, administered until completion of 6 cycles (1 cycle=4 weeks)
    Measure Participants 49 106 18 93 43
    Number [Percent of Participants]
    14.3
    29.2%
    23.6
    22.7%
    5.6
    32.9%
    11.8
    13.4%
    14.0
    37.8%
    7. Secondary Outcome
    Title Percentage of Participants Experiencing Death
    Description This outcome measure describes the percentage of participants who died (due to any cause) during the specified time frame
    Time Frame From first dose to up to 45 months following first dose

    Outcome Measure Data

    Analysis Population Description
    All treated participants. 14 participants, after receiving initial treatment, were re-randomized to a second, different treatment. They were analyzed under both groups they received treatment for.
    Arm/Group Title Nivolumab Nivolumab + Dasatinib Nivolumab + BMS986016 Nivolumab + Ipilimumab Nivolumab + BMS986205
    Arm/Group Description Nivolumab monotherapy 240 mg Q2W administered until completion of 6 cycles (1 cycle=4 weeks) Nivolumab 240 mg Q2W + Dasatinib 100 mg QD, administered until completion of 6 cycles (1 cycle=4 weeks) Nivolumab 240 mg Q2W + BMS986016 20 mg Q2W, administered until completion of 6 cycles (1 cycle=4 weeks) Nivolumab 240 mg Q2W for 12 doses + Ipilimumab 1 mg/kg Q6W for 4 doses, administered until completion of 24 weeks of study Nivolumab 480 mg Q4W + BMS986205 100 mg QD, administered until completion of 6 cycles (1 cycle=4 weeks)
    Measure Participants 49 106 18 93 43
    Number [Percent of Participants]
    57.1
    116.5%
    55.7
    53.6%
    66.7
    392.4%
    46.2
    52.5%
    62.8
    169.7%
    8. Secondary Outcome
    Title Number of Participants Experiencing Laboratory Abnormalities in Hepatic Tests
    Description The following measurements will be considered laboratory abnormalities for hepatic tests: ALT or AST > 3 x ULN, > 5 x ULN, > 10 x ULN and > 20 x ULN Total bilirubin > 2 x ULN Concurrent (within 1 day) ALT or AST > 3 x ULN and total bilirubin > 2 x ULN Concurrent (within 30 days) ALT or AST > 3 x ULN and total bilirubin > 2 x ULN ALT=Alanine aminotransferase AST=Aspartate aminotransferase ULN=Upper Limit of Normal
    Time Frame From first dose to 100 days following last dose (approximately 9 months)

    Outcome Measure Data

    Analysis Population Description
    All treated participants with available measurements. 14 participants, after receiving initial treatment, were re-randomized to a second, different treatment. When measurements were available, these participants were analyzed under both groups they received treatment for.
    Arm/Group Title Nivolumab Nivolumab + Dasatinib Nivolumab + BMS986016 Nivolumab + Ipilimumab Nivolumab + BMS986205
    Arm/Group Description Nivolumab monotherapy 240 mg Q2W administered until completion of 6 cycles (1 cycle=4 weeks) Nivolumab 240 mg Q2W + Dasatinib 100 mg QD, administered until completion of 6 cycles (1 cycle=4 weeks) Nivolumab 240 mg Q2W + BMS986016 20 mg Q2W, administered until completion of 6 cycles (1 cycle=4 weeks) Nivolumab 240 mg Q2W for 12 doses + Ipilimumab 1 mg/kg Q6W for 4 doses, administered until completion of 24 weeks of study Nivolumab 480 mg Q4W + BMS986205 100 mg QD, administered until completion of 6 cycles (1 cycle=4 weeks)
    Measure Participants 48 97 18 91 43
    ALT OR AST > 3XULN
    4
    8.2%
    3
    2.9%
    1
    5.9%
    5
    5.7%
    3
    8.1%
    ALT OR AST > 5XULN
    2
    4.1%
    0
    0%
    0
    0%
    3
    3.4%
    2
    5.4%
    ALT OR AST > 10XULN
    2
    4.1%
    0
    0%
    0
    0%
    1
    1.1%
    2
    5.4%
    ALT OR AST > 20XULN
    0
    0%
    0
    0%
    0
    0%
    1
    1.1%
    1
    2.7%
    TOTAL BILIRUBIN > 2XULN
    1
    2%
    0
    0%
    0
    0%
    2
    2.3%
    3
    8.1%
    Concurrent (within 1 day) ALT or AST > 3 x ULN and total bilirubin > 2 x ULN
    0
    0%
    0
    0%
    0
    0%
    2
    2.3%
    2
    5.4%
    Concurrent (within 30 days) ALT or AST > 3 x ULN and total bilirubin > 2 x ULN
    0
    0%
    0
    0%
    0
    0%
    2
    2.3%
    2
    5.4%
    9. Secondary Outcome
    Title Number of Participants Experiencing Laboratory Abnormalities in Thyroid Tests
    Description The following measurements will be considered laboratory abnormalities for thyroid tests: TSH value > ULN and With baseline TSH value ≤ ULN At least one T3/T4 test value < LLN Low TSH < LLN and With baseline TSH value ≥ LLN At least one T3/T4 test value > ULN TSH = thyroid stimulating hormone ULN=Upper Limit of Normal LLN=Lower Limit of Normal T3=Triiodothyronine T4=Thyroxine
    Time Frame From first dose to 100 days following last dose (approximately 9 months)

    Outcome Measure Data

    Analysis Population Description
    All treated participants with available measurements. 14 participants, after receiving initial treatment, were re-randomized to a second, different treatment. When measurements were available, these participants were analyzed under both groups they received treatment for.
    Arm/Group Title Nivolumab Nivolumab + Dasatinib Nivolumab + BMS986016 Nivolumab + Ipilimumab Nivolumab + BMS986205
    Arm/Group Description Nivolumab monotherapy 240 mg Q2W administered until completion of 6 cycles (1 cycle=4 weeks) Nivolumab 240 mg Q2W + Dasatinib 100 mg QD, administered until completion of 6 cycles (1 cycle=4 weeks) Nivolumab 240 mg Q2W + BMS986016 20 mg Q2W, administered until completion of 6 cycles (1 cycle=4 weeks) Nivolumab 240 mg Q2W for 12 doses + Ipilimumab 1 mg/kg Q6W for 4 doses, administered until completion of 24 weeks of study Nivolumab 480 mg Q4W + BMS986205 100 mg QD, administered until completion of 6 cycles (1 cycle=4 weeks)
    Measure Participants 29 76 14 75 35
    TSH > ULN
    9
    18.4%
    16
    15.4%
    3
    17.6%
    24
    27.3%
    9
    24.3%
    TSH > ULN WITH TSH <= ULN AT BASELINE
    6
    12.2%
    9
    8.7%
    1
    5.9%
    17
    19.3%
    6
    16.2%
    TSH > ULN WITH AT LEAST ONE FT3/FT4 TEST VALUE < LLN
    4
    8.2%
    3
    2.9%
    1
    5.9%
    8
    9.1%
    6
    16.2%
    TSH < LLN
    5
    10.2%
    3
    2.9%
    0
    0%
    20
    22.7%
    4
    10.8%
    TSH < LLN WITH TSH >= LLN AT BASELINE
    5
    10.2%
    1
    1%
    0
    0%
    16
    18.2%
    4
    10.8%
    TSH < LLN WITH AT LEAST ONE FT3/FT4 TEST VALUE > ULN
    3
    6.1%
    1
    1%
    0
    0%
    5
    5.7%
    0
    0%

    Adverse Events

    Time Frame All cause mortality: from first dose to up to 45 months after first dose SAEs and AEs: from first dose to 100 days following last dose
    Adverse Event Reporting Description Results are presented by study track. Track 1 = naive for prior immuno-oncology (IO) therapy and PD-L1 positive Track 2 = naive for prior immuno-oncology (IO) therapy and PD-L1 negative Track 3 = with prior anti-PD-1/PD-L1 therapy Track 4 = naive for prior anti-PD-1/PD-L1 therapy (established upon enrollment closure of tracks 1,2 and 3) Track 5 = with prior anti-PD-1/PD-L1 therapy (established upon enrollment closure of tracks 1,2 and 3).
    Arm/Group Title Track 1 - Nivolumab Track 1 - Nivolumab + Dasatinib Track 1 - Nivolumab + Ipilimumab Track 2 - Nivolumab Track 2 - Nivolumab + Dasatinib Track 2 - Nivolumab + BMS986016 Track 2 - Nivolumab + Ipilimumab Track 3 - Nivolumab + Dasatinib Track 3 - Nivolumab + BMS986016 Track 3 - Nivolumab + Ipilimumab Track 4 - Nivolumab + Dasatinib Track 4 - Nivolumab + Ipilimumab Track 5 - Nivolumab + BMS986205
    Arm/Group Description Nivolumab monotherapy 240 mg Q2W administered until completion of 6 cycles (1 cycle=4 weeks) Nivolumab 240 mg Q2W + Dasatinib 100 mg QD, administered until completion of 6 cycles (1 cycle=4 weeks) Nivolumab 240 mg Q2W for 12 doses + Ipilimumab 1 mg/kg Q6W for 4 doses, administered until completion of 24 weeks of study Nivolumab monotherapy 240 mg Q2W administered until completion of 6 cycles (1 cycle=4 weeks) Nivolumab 240 mg Q2W + Dasatinib 100 mg QD, administered until completion of 6 cycles (1 cycle=4 weeks) Nivolumab 240 mg Q2W + BMS986016 20 mg Q2W, administered until completion of 6 cycles (1 cycle=4 weeks) Nivolumab 240 mg Q2W for 12 doses + Ipilimumab 1 mg/kg Q6W for 4 doses, administered until completion of 24 weeks of study Nivolumab 240 mg Q2W + Dasatinib 100 mg QD, administered until completion of 6 cycles (1 cycle=4 weeks) Nivolumab 240 mg Q2W + BMS986016 20 mg Q2W, administered until completion of 6 cycles (1 cycle=4 weeks) Nivolumab 240 mg Q2W for 12 doses + Ipilimumab 1 mg/kg Q6W for 4 doses, administered until completion of 24 weeks of study Nivolumab 240 mg Q2W + Dasatinib 100 mg QD, administered until completion of 6 cycles (1 cycle=4 weeks) Nivolumab 240 mg Q2W for 12 doses + Ipilimumab 1 mg/kg Q6W for 4 doses, administered until completion of 24 weeks of study Nivolumab 480 mg Q4W + BMS986205 100 mg QD, administered until completion of 6 cycles (1 cycle=4 weeks)
    All Cause Mortality
    Track 1 - Nivolumab Track 1 - Nivolumab + Dasatinib Track 1 - Nivolumab + Ipilimumab Track 2 - Nivolumab Track 2 - Nivolumab + Dasatinib Track 2 - Nivolumab + BMS986016 Track 2 - Nivolumab + Ipilimumab Track 3 - Nivolumab + Dasatinib Track 3 - Nivolumab + BMS986016 Track 3 - Nivolumab + Ipilimumab Track 4 - Nivolumab + Dasatinib Track 4 - Nivolumab + Ipilimumab Track 5 - Nivolumab + BMS986205
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 22/40 (55%) 2/4 (50%) 1/3 (33.3%) 6/9 (66.7%) 4/8 (50%) 2/2 (100%) 6/12 (50%) 20/41 (48.8%) 10/16 (62.5%) 9/18 (50%) 33/53 (62.3%) 27/60 (45%) 27/43 (62.8%)
    Serious Adverse Events
    Track 1 - Nivolumab Track 1 - Nivolumab + Dasatinib Track 1 - Nivolumab + Ipilimumab Track 2 - Nivolumab Track 2 - Nivolumab + Dasatinib Track 2 - Nivolumab + BMS986016 Track 2 - Nivolumab + Ipilimumab Track 3 - Nivolumab + Dasatinib Track 3 - Nivolumab + BMS986016 Track 3 - Nivolumab + Ipilimumab Track 4 - Nivolumab + Dasatinib Track 4 - Nivolumab + Ipilimumab Track 5 - Nivolumab + BMS986205
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 24/40 (60%) 2/4 (50%) 0/3 (0%) 4/9 (44.4%) 5/8 (62.5%) 2/2 (100%) 5/12 (41.7%) 17/41 (41.5%) 9/16 (56.3%) 10/18 (55.6%) 33/53 (62.3%) 39/60 (65%) 26/43 (60.5%)
    Blood and lymphatic system disorders
    Neutropenia 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 1/60 (1.7%) 1/43 (2.3%)
    Cardiac disorders
    Atrial fibrillation 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 1/18 (5.6%) 1/53 (1.9%) 2/60 (3.3%) 1/43 (2.3%)
    Atrial flutter 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 1/2 (50%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 1/60 (1.7%) 0/43 (0%)
    Cardiac arrest 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 1/53 (1.9%) 0/60 (0%) 0/43 (0%)
    Cardiac tamponade 1/40 (2.5%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Myocarditis 1/40 (2.5%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Pericardial effusion 3/40 (7.5%) 1/4 (25%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 1/60 (1.7%) 0/43 (0%)
    Supraventricular tachycardia 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 1/60 (1.7%) 1/43 (2.3%)
    Tachycardia 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 1/60 (1.7%) 0/43 (0%)
    Endocrine disorders
    Adrenal insufficiency 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 1/41 (2.4%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Hypoparathyroidism 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 1/60 (1.7%) 0/43 (0%)
    Hypophysitis 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 1/60 (1.7%) 0/43 (0%)
    Eye disorders
    Vision blurred 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 1/43 (2.3%)
    Visual impairment 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 1/43 (2.3%)
    Gastrointestinal disorders
    Abdominal pain 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 1/18 (5.6%) 0/53 (0%) 0/60 (0%) 1/43 (2.3%)
    Colitis 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 1/12 (8.3%) 1/41 (2.4%) 0/16 (0%) 0/18 (0%) 1/53 (1.9%) 0/60 (0%) 0/43 (0%)
    Constipation 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 1/43 (2.3%)
    Diarrhoea 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 1/41 (2.4%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 2/60 (3.3%) 0/43 (0%)
    Large intestinal obstruction 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 1/16 (6.3%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Nausea 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 3/53 (5.7%) 0/60 (0%) 0/43 (0%)
    Oesophageal food impaction 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 1/8 (12.5%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Peritoneal haemorrhage 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 1/12 (8.3%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Vomiting 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 1/53 (1.9%) 0/60 (0%) 0/43 (0%)
    General disorders
    Euthanasia 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 1/53 (1.9%) 0/60 (0%) 0/43 (0%)
    Fatigue 1/40 (2.5%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 2/41 (4.9%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    General physical health deterioration 0/40 (0%) 0/4 (0%) 0/3 (0%) 1/9 (11.1%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Influenza like illness 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 1/43 (2.3%)
    Oedema peripheral 1/40 (2.5%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Pain 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 1/41 (2.4%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Pyrexia 0/40 (0%) 1/4 (25%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 2/53 (3.8%) 3/60 (5%) 0/43 (0%)
    Hepatobiliary disorders
    Cholecystitis acute 1/40 (2.5%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Hepatitis 2/40 (5%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Hyperbilirubinaemia 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 1/43 (2.3%)
    Infections and infestations
    Appendicitis 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 1/60 (1.7%) 0/43 (0%)
    Brain abscess 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 1/41 (2.4%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Clostridium difficile colitis 1/40 (2.5%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Enterocolitis infectious 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 1/16 (6.3%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Influenza 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 1/43 (2.3%)
    Pharyngitis streptococcal 1/40 (2.5%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Pneumonia 2/40 (5%) 1/4 (25%) 0/3 (0%) 1/9 (11.1%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 1/41 (2.4%) 0/16 (0%) 2/18 (11.1%) 0/53 (0%) 3/60 (5%) 1/43 (2.3%)
    Pneumonia bacterial 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 1/60 (1.7%) 0/43 (0%)
    Post procedural infection 0/40 (0%) 1/4 (25%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Respiratory tract infection 1/40 (2.5%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 1/41 (2.4%) 0/16 (0%) 1/18 (5.6%) 0/53 (0%) 1/60 (1.7%) 0/43 (0%)
    Sepsis 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 1/16 (6.3%) 0/18 (0%) 1/53 (1.9%) 2/60 (3.3%) 1/43 (2.3%)
    Septic shock 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 1/41 (2.4%) 0/16 (0%) 0/18 (0%) 1/53 (1.9%) 0/60 (0%) 0/43 (0%)
    Staphylococcal infection 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 1/43 (2.3%)
    Urinary tract infection 1/40 (2.5%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Injury, poisoning and procedural complications
    Ankle fracture 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 1/53 (1.9%) 0/60 (0%) 0/43 (0%)
    Fall 1/40 (2.5%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Humerus fracture 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 1/53 (1.9%) 1/60 (1.7%) 0/43 (0%)
    Infusion related reaction 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 1/53 (1.9%) 0/60 (0%) 0/43 (0%)
    Overdose 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 1/41 (2.4%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 1/60 (1.7%) 2/43 (4.7%)
    Subdural haematoma 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 1/12 (8.3%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Toxicity to various agents 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 1/60 (1.7%) 0/43 (0%)
    Investigations
    Blood bilirubin increased 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 1/43 (2.3%)
    Blood creatine phosphokinase increased 1/40 (2.5%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Human chorionic gonadotropin positive 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 1/60 (1.7%) 0/43 (0%)
    Transaminases increased 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 1/60 (1.7%) 0/43 (0%)
    Metabolism and nutrition disorders
    Dehydration 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 1/16 (6.3%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Diabetes mellitus 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 1/12 (8.3%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Diabetic ketoacidosis 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 1/60 (1.7%) 0/43 (0%)
    Failure to thrive 1/40 (2.5%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 1/41 (2.4%) 1/16 (6.3%) 0/18 (0%) 0/53 (0%) 1/60 (1.7%) 0/43 (0%)
    Hypercalcaemia 1/40 (2.5%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 1/18 (5.6%) 2/53 (3.8%) 0/60 (0%) 0/43 (0%)
    Hyperglycaemia 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 1/43 (2.3%)
    Hyponatraemia 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 1/41 (2.4%) 0/16 (0%) 0/18 (0%) 1/53 (1.9%) 1/60 (1.7%) 1/43 (2.3%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 2/40 (5%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Back pain 1/40 (2.5%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 1/43 (2.3%)
    Flank pain 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 1/43 (2.3%)
    Muscular weakness 1/40 (2.5%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 1/12 (8.3%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 1/43 (2.3%)
    Musculoskeletal chest pain 1/40 (2.5%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Osteolysis 1/40 (2.5%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Pain in extremity 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 1/43 (2.3%)
    Sjogren's syndrome 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 1/60 (1.7%) 0/43 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Basal cell carcinoma 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 1/60 (1.7%) 0/43 (0%)
    Cancer pain 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 1/8 (12.5%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Lung neoplasm malignant 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 1/53 (1.9%) 0/60 (0%) 0/43 (0%)
    Malignant neoplasm progression 10/40 (25%) 0/4 (0%) 0/3 (0%) 2/9 (22.2%) 1/8 (12.5%) 1/2 (50%) 1/12 (8.3%) 9/41 (22%) 3/16 (18.8%) 3/18 (16.7%) 19/53 (35.8%) 16/60 (26.7%) 13/43 (30.2%)
    Malignant pleural effusion 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 2/60 (3.3%) 0/43 (0%)
    Metastases to meninges 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 1/60 (1.7%) 0/43 (0%)
    Neoplasm progression 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 1/43 (2.3%)
    Second primary malignancy 1/40 (2.5%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Tumour pain 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 1/16 (6.3%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Nervous system disorders
    Brachial plexopathy 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 1/53 (1.9%) 0/60 (0%) 0/43 (0%)
    Cerebral ischaemia 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 1/60 (1.7%) 0/43 (0%)
    Cerebrovascular accident 1/40 (2.5%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 1/16 (6.3%) 0/18 (0%) 1/53 (1.9%) 0/60 (0%) 1/43 (2.3%)
    Dizziness 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 1/53 (1.9%) 0/60 (0%) 0/43 (0%)
    Facial paralysis 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 1/43 (2.3%)
    Haemorrhage intracranial 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 1/53 (1.9%) 0/60 (0%) 0/43 (0%)
    Headache 1/40 (2.5%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Ischaemic stroke 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 1/16 (6.3%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Peripheral sensory neuropathy 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 2/43 (4.7%)
    Polyneuropathy 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 1/60 (1.7%) 0/43 (0%)
    Seizure 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 1/53 (1.9%) 1/60 (1.7%) 1/43 (2.3%)
    Spinal cord compression 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 1/60 (1.7%) 0/43 (0%)
    Psychiatric disorders
    Confusional state 2/40 (5%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 1/53 (1.9%) 0/60 (0%) 1/43 (2.3%)
    Delirium 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 1/41 (2.4%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Mental status changes 1/40 (2.5%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 1/53 (1.9%) 0/60 (0%) 0/43 (0%)
    Renal and urinary disorders
    Acute kidney injury 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 1/41 (2.4%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 2/60 (3.3%) 0/43 (0%)
    Reproductive system and breast disorders
    Scrotal oedema 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 1/41 (2.4%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory failure 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 1/12 (8.3%) 1/41 (2.4%) 0/16 (0%) 1/18 (5.6%) 0/53 (0%) 2/60 (3.3%) 1/43 (2.3%)
    Atelectasis 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 1/18 (5.6%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Bronchial obstruction 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 1/18 (5.6%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Chronic obstructive pulmonary disease 2/40 (5%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 1/16 (6.3%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Dyspnoea 2/40 (5%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 3/41 (7.3%) 0/16 (0%) 2/18 (11.1%) 4/53 (7.5%) 3/60 (5%) 0/43 (0%)
    Haemoptysis 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 1/8 (12.5%) 0/2 (0%) 1/12 (8.3%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 1/53 (1.9%) 1/60 (1.7%) 0/43 (0%)
    Hypoxia 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 1/8 (12.5%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 1/53 (1.9%) 1/60 (1.7%) 0/43 (0%)
    Interstitial lung disease 0/40 (0%) 0/4 (0%) 0/3 (0%) 1/9 (11.1%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Lung consolidation 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 1/18 (5.6%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Oesophagobronchial fistula 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 1/60 (1.7%) 0/43 (0%)
    Pleural effusion 2/40 (5%) 1/4 (25%) 0/3 (0%) 0/9 (0%) 2/8 (25%) 0/2 (0%) 0/12 (0%) 1/41 (2.4%) 0/16 (0%) 1/18 (5.6%) 3/53 (5.7%) 2/60 (3.3%) 1/43 (2.3%)
    Pneumonitis 3/40 (7.5%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 1/8 (12.5%) 1/2 (50%) 0/12 (0%) 1/41 (2.4%) 0/16 (0%) 0/18 (0%) 4/53 (7.5%) 3/60 (5%) 3/43 (7%)
    Pneumothorax 1/40 (2.5%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 1/53 (1.9%) 0/60 (0%) 1/43 (2.3%)
    Pulmonary embolism 4/40 (10%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 1/2 (50%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 1/60 (1.7%) 1/43 (2.3%)
    Respiratory distress 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 1/12 (8.3%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 1/53 (1.9%) 0/60 (0%) 0/43 (0%)
    Respiratory failure 1/40 (2.5%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 2/41 (4.9%) 0/16 (0%) 1/18 (5.6%) 0/53 (0%) 0/60 (0%) 1/43 (2.3%)
    Skin and subcutaneous tissue disorders
    Stevens-Johnson syndrome 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 1/60 (1.7%) 0/43 (0%)
    Vascular disorders
    Deep vein thrombosis 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 1/60 (1.7%) 0/43 (0%)
    Hypotension 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 1/41 (2.4%) 0/16 (0%) 1/18 (5.6%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Orthostatic hypotension 1/40 (2.5%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Superior vena cava syndrome 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 1/16 (6.3%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Other (Not Including Serious) Adverse Events
    Track 1 - Nivolumab Track 1 - Nivolumab + Dasatinib Track 1 - Nivolumab + Ipilimumab Track 2 - Nivolumab Track 2 - Nivolumab + Dasatinib Track 2 - Nivolumab + BMS986016 Track 2 - Nivolumab + Ipilimumab Track 3 - Nivolumab + Dasatinib Track 3 - Nivolumab + BMS986016 Track 3 - Nivolumab + Ipilimumab Track 4 - Nivolumab + Dasatinib Track 4 - Nivolumab + Ipilimumab Track 5 - Nivolumab + BMS986205
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 38/40 (95%) 4/4 (100%) 3/3 (100%) 9/9 (100%) 7/8 (87.5%) 2/2 (100%) 12/12 (100%) 38/41 (92.7%) 16/16 (100%) 17/18 (94.4%) 50/53 (94.3%) 59/60 (98.3%) 41/43 (95.3%)
    Blood and lymphatic system disorders
    Anaemia 7/40 (17.5%) 1/4 (25%) 0/3 (0%) 1/9 (11.1%) 3/8 (37.5%) 0/2 (0%) 3/12 (25%) 6/41 (14.6%) 2/16 (12.5%) 1/18 (5.6%) 15/53 (28.3%) 10/60 (16.7%) 6/43 (14%)
    Leukocytosis 1/40 (2.5%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 1/41 (2.4%) 0/16 (0%) 0/18 (0%) 1/53 (1.9%) 4/60 (6.7%) 1/43 (2.3%)
    Leukopenia 0/40 (0%) 1/4 (25%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 1/53 (1.9%) 0/60 (0%) 0/43 (0%)
    Lymphadenopathy 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 1/12 (8.3%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 1/53 (1.9%) 0/60 (0%) 1/43 (2.3%)
    Lymphopenia 1/40 (2.5%) 1/4 (25%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 1/53 (1.9%) 2/60 (3.3%) 0/43 (0%)
    Neutropenia 2/40 (5%) 1/4 (25%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 2/60 (3.3%) 0/43 (0%)
    Thrombocytopenia 0/40 (0%) 1/4 (25%) 0/3 (0%) 1/9 (11.1%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 1/41 (2.4%) 0/16 (0%) 0/18 (0%) 3/53 (5.7%) 3/60 (5%) 1/43 (2.3%)
    Cardiac disorders
    Arrhythmia 0/40 (0%) 1/4 (25%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 1/53 (1.9%) 0/60 (0%) 0/43 (0%)
    Atrial fibrillation 0/40 (0%) 1/4 (25%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 1/18 (5.6%) 2/53 (3.8%) 2/60 (3.3%) 1/43 (2.3%)
    Bradycardia 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 1/12 (8.3%) 1/41 (2.4%) 0/16 (0%) 0/18 (0%) 1/53 (1.9%) 1/60 (1.7%) 0/43 (0%)
    Cardiac tamponade 0/40 (0%) 1/4 (25%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Tachycardia 2/40 (5%) 1/4 (25%) 0/3 (0%) 1/9 (11.1%) 1/8 (12.5%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 2/53 (3.8%) 5/60 (8.3%) 1/43 (2.3%)
    Ear and labyrinth disorders
    Ear discomfort 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 1/8 (12.5%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Vertigo 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 1/8 (12.5%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 1/53 (1.9%) 0/60 (0%) 2/43 (4.7%)
    Endocrine disorders
    Hyperthyroidism 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 1/16 (6.3%) 1/18 (5.6%) 2/53 (3.8%) 2/60 (3.3%) 0/43 (0%)
    Hypophysitis 0/40 (0%) 1/4 (25%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 1/41 (2.4%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 1/60 (1.7%) 0/43 (0%)
    Hypothyroidism 4/40 (10%) 0/4 (0%) 1/3 (33.3%) 0/9 (0%) 1/8 (12.5%) 0/2 (0%) 2/12 (16.7%) 2/41 (4.9%) 0/16 (0%) 0/18 (0%) 1/53 (1.9%) 6/60 (10%) 1/43 (2.3%)
    Thyroiditis 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 1/12 (8.3%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 1/60 (1.7%) 0/43 (0%)
    Eye disorders
    Cataract 0/40 (0%) 1/4 (25%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 1/18 (5.6%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Eye pain 0/40 (0%) 0/4 (0%) 1/3 (33.3%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Vision blurred 3/40 (7.5%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 2/12 (16.7%) 0/41 (0%) 0/16 (0%) 1/18 (5.6%) 3/53 (5.7%) 2/60 (3.3%) 1/43 (2.3%)
    Visual acuity reduced 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 1/8 (12.5%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Visual impairment 0/40 (0%) 0/4 (0%) 1/3 (33.3%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 1/41 (2.4%) 0/16 (0%) 0/18 (0%) 2/53 (3.8%) 1/60 (1.7%) 2/43 (4.7%)
    Vitreous floaters 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 1/41 (2.4%) 0/16 (0%) 1/18 (5.6%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Gastrointestinal disorders
    Abdominal discomfort 0/40 (0%) 0/4 (0%) 0/3 (0%) 1/9 (11.1%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 1/41 (2.4%) 1/16 (6.3%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 2/43 (4.7%)
    Abdominal distension 1/40 (2.5%) 0/4 (0%) 1/3 (33.3%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 2/12 (16.7%) 0/41 (0%) 0/16 (0%) 1/18 (5.6%) 1/53 (1.9%) 1/60 (1.7%) 2/43 (4.7%)
    Abdominal pain 5/40 (12.5%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 1/12 (8.3%) 6/41 (14.6%) 2/16 (12.5%) 5/18 (27.8%) 5/53 (9.4%) 6/60 (10%) 6/43 (14%)
    Abdominal pain upper 2/40 (5%) 1/4 (25%) 0/3 (0%) 1/9 (11.1%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 2/18 (11.1%) 0/53 (0%) 2/60 (3.3%) 2/43 (4.7%)
    Anal incontinence 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 1/18 (5.6%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Ascites 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 1/18 (5.6%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Autoimmune colitis 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 1/12 (8.3%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Colitis 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 1/12 (8.3%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 1/53 (1.9%) 1/60 (1.7%) 0/43 (0%)
    Constipation 9/40 (22.5%) 3/4 (75%) 3/3 (100%) 0/9 (0%) 1/8 (12.5%) 0/2 (0%) 3/12 (25%) 9/41 (22%) 1/16 (6.3%) 2/18 (11.1%) 20/53 (37.7%) 18/60 (30%) 13/43 (30.2%)
    Diarrhoea 13/40 (32.5%) 0/4 (0%) 1/3 (33.3%) 2/9 (22.2%) 4/8 (50%) 0/2 (0%) 4/12 (33.3%) 8/41 (19.5%) 5/16 (31.3%) 2/18 (11.1%) 20/53 (37.7%) 17/60 (28.3%) 11/43 (25.6%)
    Dry mouth 1/40 (2.5%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 2/16 (12.5%) 1/18 (5.6%) 1/53 (1.9%) 4/60 (6.7%) 0/43 (0%)
    Dyspepsia 2/40 (5%) 0/4 (0%) 0/3 (0%) 1/9 (11.1%) 0/8 (0%) 0/2 (0%) 1/12 (8.3%) 1/41 (2.4%) 1/16 (6.3%) 2/18 (11.1%) 2/53 (3.8%) 1/60 (1.7%) 1/43 (2.3%)
    Dysphagia 1/40 (2.5%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 1/8 (12.5%) 0/2 (0%) 1/12 (8.3%) 1/41 (2.4%) 0/16 (0%) 1/18 (5.6%) 1/53 (1.9%) 1/60 (1.7%) 2/43 (4.7%)
    Faeces discoloured 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 1/18 (5.6%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Flatulence 2/40 (5%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 1/41 (2.4%) 0/16 (0%) 1/18 (5.6%) 0/53 (0%) 2/60 (3.3%) 0/43 (0%)
    Mouth ulceration 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 1/16 (6.3%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Nausea 14/40 (35%) 3/4 (75%) 2/3 (66.7%) 3/9 (33.3%) 4/8 (50%) 0/2 (0%) 3/12 (25%) 16/41 (39%) 3/16 (18.8%) 4/18 (22.2%) 22/53 (41.5%) 18/60 (30%) 16/43 (37.2%)
    Oesophageal mucosa erythema 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 1/8 (12.5%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Oesophagitis 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 1/12 (8.3%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 1/53 (1.9%) 0/60 (0%) 0/43 (0%)
    Pancreatitis 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 1/18 (5.6%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Peritoneal haemorrhage 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 1/12 (8.3%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Rectal haemorrhage 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 1/12 (8.3%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Stomatitis 0/40 (0%) 0/4 (0%) 0/3 (0%) 1/9 (11.1%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 3/41 (7.3%) 2/16 (12.5%) 0/18 (0%) 1/53 (1.9%) 0/60 (0%) 3/43 (7%)
    Tongue dysplasia 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 1/16 (6.3%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Toothache 0/40 (0%) 0/4 (0%) 1/3 (33.3%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 1/41 (2.4%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 1/43 (2.3%)
    Vomiting 8/40 (20%) 1/4 (25%) 0/3 (0%) 1/9 (11.1%) 3/8 (37.5%) 0/2 (0%) 3/12 (25%) 8/41 (19.5%) 1/16 (6.3%) 3/18 (16.7%) 14/53 (26.4%) 14/60 (23.3%) 5/43 (11.6%)
    General disorders
    Asthenia 5/40 (12.5%) 2/4 (50%) 0/3 (0%) 2/9 (22.2%) 1/8 (12.5%) 0/2 (0%) 0/12 (0%) 4/41 (9.8%) 0/16 (0%) 0/18 (0%) 11/53 (20.8%) 11/60 (18.3%) 1/43 (2.3%)
    Chest discomfort 0/40 (0%) 0/4 (0%) 1/3 (33.3%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 1/41 (2.4%) 2/16 (12.5%) 1/18 (5.6%) 1/53 (1.9%) 1/60 (1.7%) 1/43 (2.3%)
    Chest pain 3/40 (7.5%) 1/4 (25%) 0/3 (0%) 1/9 (11.1%) 1/8 (12.5%) 1/2 (50%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 2/18 (11.1%) 5/53 (9.4%) 3/60 (5%) 2/43 (4.7%)
    Chills 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 4/41 (9.8%) 1/16 (6.3%) 2/18 (11.1%) 7/53 (13.2%) 3/60 (5%) 1/43 (2.3%)
    Early satiety 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 1/8 (12.5%) 0/2 (0%) 0/12 (0%) 1/41 (2.4%) 1/16 (6.3%) 1/18 (5.6%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Face oedema 1/40 (2.5%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 4/53 (7.5%) 0/60 (0%) 1/43 (2.3%)
    Fatigue 16/40 (40%) 1/4 (25%) 0/3 (0%) 1/9 (11.1%) 4/8 (50%) 0/2 (0%) 6/12 (50%) 19/41 (46.3%) 5/16 (31.3%) 8/18 (44.4%) 27/53 (50.9%) 30/60 (50%) 20/43 (46.5%)
    Influenza like illness 2/40 (5%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 3/41 (7.3%) 0/16 (0%) 0/18 (0%) 1/53 (1.9%) 2/60 (3.3%) 0/43 (0%)
    Malaise 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 1/18 (5.6%) 0/53 (0%) 1/60 (1.7%) 0/43 (0%)
    Mucosal inflammation 2/40 (5%) 1/4 (25%) 0/3 (0%) 0/9 (0%) 1/8 (12.5%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 1/18 (5.6%) 1/53 (1.9%) 1/60 (1.7%) 0/43 (0%)
    Non-cardiac chest pain 1/40 (2.5%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 1/12 (8.3%) 3/41 (7.3%) 0/16 (0%) 2/18 (11.1%) 3/53 (5.7%) 2/60 (3.3%) 0/43 (0%)
    Oedema 0/40 (0%) 2/4 (50%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 1/41 (2.4%) 0/16 (0%) 0/18 (0%) 4/53 (7.5%) 1/60 (1.7%) 2/43 (4.7%)
    Oedema peripheral 7/40 (17.5%) 1/4 (25%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 5/41 (12.2%) 1/16 (6.3%) 1/18 (5.6%) 2/53 (3.8%) 7/60 (11.7%) 7/43 (16.3%)
    Pain 1/40 (2.5%) 0/4 (0%) 0/3 (0%) 1/9 (11.1%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 3/41 (7.3%) 0/16 (0%) 2/18 (11.1%) 0/53 (0%) 2/60 (3.3%) 0/43 (0%)
    Pyrexia 3/40 (7.5%) 2/4 (50%) 0/3 (0%) 1/9 (11.1%) 2/8 (25%) 0/2 (0%) 2/12 (16.7%) 4/41 (9.8%) 1/16 (6.3%) 3/18 (16.7%) 10/53 (18.9%) 10/60 (16.7%) 5/43 (11.6%)
    Hepatobiliary disorders
    Cholelithiasis 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 1/16 (6.3%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Hepatic failure 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 1/18 (5.6%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Jaundice 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 1/18 (5.6%) 0/53 (0%) 0/60 (0%) 2/43 (4.7%)
    Immune system disorders
    Hypersensitivity 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 1/8 (12.5%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 1/16 (6.3%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Seasonal allergy 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 1/12 (8.3%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 1/53 (1.9%) 0/60 (0%) 0/43 (0%)
    Infections and infestations
    Abscess 0/40 (0%) 0/4 (0%) 1/3 (33.3%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Bronchitis 1/40 (2.5%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 1/16 (6.3%) 1/18 (5.6%) 1/53 (1.9%) 2/60 (3.3%) 0/43 (0%)
    Candida infection 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 1/53 (1.9%) 4/60 (6.7%) 0/43 (0%)
    Conjunctivitis 1/40 (2.5%) 1/4 (25%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 1/41 (2.4%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Cystitis 1/40 (2.5%) 1/4 (25%) 1/3 (33.3%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 1/53 (1.9%) 0/60 (0%) 0/43 (0%)
    Diverticulitis 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 1/18 (5.6%) 1/53 (1.9%) 1/60 (1.7%) 0/43 (0%)
    Eye infection 0/40 (0%) 1/4 (25%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Influenza 2/40 (5%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 1/60 (1.7%) 3/43 (7%)
    Laryngitis 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 1/16 (6.3%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Lung abscess 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 1/18 (5.6%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Nasopharyngitis 2/40 (5%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 1/41 (2.4%) 0/16 (0%) 0/18 (0%) 5/53 (9.4%) 2/60 (3.3%) 1/43 (2.3%)
    Oral candidiasis 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 1/8 (12.5%) 0/2 (0%) 0/12 (0%) 1/41 (2.4%) 0/16 (0%) 0/18 (0%) 1/53 (1.9%) 1/60 (1.7%) 1/43 (2.3%)
    Otitis externa 0/40 (0%) 0/4 (0%) 0/3 (0%) 1/9 (11.1%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Pneumonia 2/40 (5%) 0/4 (0%) 0/3 (0%) 1/9 (11.1%) 1/8 (12.5%) 0/2 (0%) 0/12 (0%) 3/41 (7.3%) 0/16 (0%) 1/18 (5.6%) 2/53 (3.8%) 2/60 (3.3%) 2/43 (4.7%)
    Rhinitis 1/40 (2.5%) 0/4 (0%) 0/3 (0%) 1/9 (11.1%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 1/53 (1.9%) 0/60 (0%) 0/43 (0%)
    Sinusitis 1/40 (2.5%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 1/41 (2.4%) 0/16 (0%) 1/18 (5.6%) 0/53 (0%) 1/60 (1.7%) 0/43 (0%)
    Upper respiratory tract infection 2/40 (5%) 0/4 (0%) 0/3 (0%) 1/9 (11.1%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 2/41 (4.9%) 1/16 (6.3%) 0/18 (0%) 2/53 (3.8%) 1/60 (1.7%) 4/43 (9.3%)
    Urinary tract infection 7/40 (17.5%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 1/12 (8.3%) 1/41 (2.4%) 0/16 (0%) 1/18 (5.6%) 1/53 (1.9%) 1/60 (1.7%) 1/43 (2.3%)
    Injury, poisoning and procedural complications
    Contusion 1/40 (2.5%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 3/41 (7.3%) 1/16 (6.3%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 2/43 (4.7%)
    Fall 0/40 (0%) 0/4 (0%) 0/3 (0%) 1/9 (11.1%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 1/41 (2.4%) 0/16 (0%) 0/18 (0%) 2/53 (3.8%) 3/60 (5%) 2/43 (4.7%)
    Infusion related reaction 0/40 (0%) 0/4 (0%) 0/3 (0%) 1/9 (11.1%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 1/41 (2.4%) 0/16 (0%) 0/18 (0%) 1/53 (1.9%) 2/60 (3.3%) 2/43 (4.7%)
    Muscle strain 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 1/18 (5.6%) 0/53 (0%) 1/60 (1.7%) 0/43 (0%)
    Procedural pain 0/40 (0%) 0/4 (0%) 0/3 (0%) 1/9 (11.1%) 1/8 (12.5%) 0/2 (0%) 0/12 (0%) 2/41 (4.9%) 0/16 (0%) 2/18 (11.1%) 0/53 (0%) 1/60 (1.7%) 0/43 (0%)
    Investigations
    Alanine aminotransferase increased 2/40 (5%) 1/4 (25%) 0/3 (0%) 2/9 (22.2%) 1/8 (12.5%) 0/2 (0%) 1/12 (8.3%) 1/41 (2.4%) 0/16 (0%) 2/18 (11.1%) 5/53 (9.4%) 2/60 (3.3%) 5/43 (11.6%)
    Amylase increased 3/40 (7.5%) 0/4 (0%) 1/3 (33.3%) 1/9 (11.1%) 0/8 (0%) 1/2 (50%) 2/12 (16.7%) 3/41 (7.3%) 0/16 (0%) 2/18 (11.1%) 5/53 (9.4%) 3/60 (5%) 0/43 (0%)
    Aspartate aminotransferase increased 4/40 (10%) 1/4 (25%) 0/3 (0%) 2/9 (22.2%) 1/8 (12.5%) 1/2 (50%) 1/12 (8.3%) 2/41 (4.9%) 0/16 (0%) 1/18 (5.6%) 3/53 (5.7%) 4/60 (6.7%) 4/43 (9.3%)
    Blood alkaline phosphatase increased 3/40 (7.5%) 0/4 (0%) 1/3 (33.3%) 0/9 (0%) 1/8 (12.5%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 1/18 (5.6%) 2/53 (3.8%) 2/60 (3.3%) 1/43 (2.3%)
    Blood bilirubin increased 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 1/18 (5.6%) 0/53 (0%) 0/60 (0%) 4/43 (9.3%)
    Blood calcium increased 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 1/12 (8.3%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Blood creatine phosphokinase increased 0/40 (0%) 0/4 (0%) 1/3 (33.3%) 1/9 (11.1%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 1/41 (2.4%) 0/16 (0%) 0/18 (0%) 1/53 (1.9%) 1/60 (1.7%) 0/43 (0%)
    Blood creatinine increased 2/40 (5%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 2/12 (16.7%) 0/41 (0%) 1/16 (6.3%) 1/18 (5.6%) 3/53 (5.7%) 2/60 (3.3%) 2/43 (4.7%)
    Blood lactate dehydrogenase increased 1/40 (2.5%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 1/8 (12.5%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Blood phosphorus decreased 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 1/8 (12.5%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Blood thyroid stimulating hormone decreased 0/40 (0%) 0/4 (0%) 1/3 (33.3%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 1/60 (1.7%) 0/43 (0%)
    Blood thyroid stimulating hormone increased 2/40 (5%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 1/12 (8.3%) 0/41 (0%) 1/16 (6.3%) 0/18 (0%) 0/53 (0%) 1/60 (1.7%) 0/43 (0%)
    Blood urea increased 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 1/12 (8.3%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Body temperature increased 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 2/18 (11.1%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    C-reactive protein increased 1/40 (2.5%) 1/4 (25%) 0/3 (0%) 1/9 (11.1%) 1/8 (12.5%) 0/2 (0%) 0/12 (0%) 2/41 (4.9%) 0/16 (0%) 0/18 (0%) 1/53 (1.9%) 3/60 (5%) 1/43 (2.3%)
    CD4 lymphocytes decreased 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 1/8 (12.5%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Electrocardiogram QT prolonged 1/40 (2.5%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 1/12 (8.3%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 2/53 (3.8%) 0/60 (0%) 0/43 (0%)
    Gamma-glutamyltransferase increased 1/40 (2.5%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 1/18 (5.6%) 3/53 (5.7%) 2/60 (3.3%) 0/43 (0%)
    Lipase increased 1/40 (2.5%) 1/4 (25%) 1/3 (33.3%) 1/9 (11.1%) 0/8 (0%) 0/2 (0%) 2/12 (16.7%) 2/41 (4.9%) 0/16 (0%) 2/18 (11.1%) 3/53 (5.7%) 3/60 (5%) 2/43 (4.7%)
    Lymphocyte count decreased 2/40 (5%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 1/8 (12.5%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 1/16 (6.3%) 1/18 (5.6%) 1/53 (1.9%) 2/60 (3.3%) 3/43 (7%)
    Neutrophil count decreased 0/40 (0%) 0/4 (0%) 1/3 (33.3%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 1/43 (2.3%)
    Transaminases increased 1/40 (2.5%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 3/53 (5.7%) 0/60 (0%) 0/43 (0%)
    Troponin T increased 0/40 (0%) 0/4 (0%) 0/3 (0%) 1/9 (11.1%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 1/53 (1.9%) 1/60 (1.7%) 0/43 (0%)
    Weight decreased 7/40 (17.5%) 2/4 (50%) 1/3 (33.3%) 0/9 (0%) 2/8 (25%) 0/2 (0%) 1/12 (8.3%) 6/41 (14.6%) 0/16 (0%) 2/18 (11.1%) 8/53 (15.1%) 11/60 (18.3%) 13/43 (30.2%)
    Weight increased 2/40 (5%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 4/60 (6.7%) 0/43 (0%)
    White blood cell count increased 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 1/8 (12.5%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 1/60 (1.7%) 0/43 (0%)
    Metabolism and nutrition disorders
    Decreased appetite 16/40 (40%) 1/4 (25%) 1/3 (33.3%) 2/9 (22.2%) 2/8 (25%) 1/2 (50%) 1/12 (8.3%) 11/41 (26.8%) 4/16 (25%) 5/18 (27.8%) 25/53 (47.2%) 17/60 (28.3%) 15/43 (34.9%)
    Dehydration 1/40 (2.5%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 2/8 (25%) 0/2 (0%) 1/12 (8.3%) 2/41 (4.9%) 0/16 (0%) 0/18 (0%) 2/53 (3.8%) 4/60 (6.7%) 4/43 (9.3%)
    Fluid retention 0/40 (0%) 1/4 (25%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Hyperamylasaemia 0/40 (0%) 1/4 (25%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 1/53 (1.9%) 2/60 (3.3%) 0/43 (0%)
    Hyperglycaemia 0/40 (0%) 0/4 (0%) 0/3 (0%) 1/9 (11.1%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 1/16 (6.3%) 0/18 (0%) 3/53 (5.7%) 4/60 (6.7%) 3/43 (7%)
    Hyperkalaemia 1/40 (2.5%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 1/41 (2.4%) 0/16 (0%) 1/18 (5.6%) 0/53 (0%) 5/60 (8.3%) 0/43 (0%)
    Hypoalbuminaemia 2/40 (5%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 1/41 (2.4%) 0/16 (0%) 1/18 (5.6%) 2/53 (3.8%) 2/60 (3.3%) 2/43 (4.7%)
    Hypocalcaemia 3/40 (7.5%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 2/53 (3.8%) 2/60 (3.3%) 0/43 (0%)
    Hypokalaemia 3/40 (7.5%) 0/4 (0%) 0/3 (0%) 1/9 (11.1%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 2/41 (4.9%) 1/16 (6.3%) 1/18 (5.6%) 4/53 (7.5%) 6/60 (10%) 2/43 (4.7%)
    Hypomagnesaemia 4/40 (10%) 0/4 (0%) 1/3 (33.3%) 1/9 (11.1%) 0/8 (0%) 0/2 (0%) 1/12 (8.3%) 4/41 (9.8%) 0/16 (0%) 2/18 (11.1%) 4/53 (7.5%) 7/60 (11.7%) 1/43 (2.3%)
    Hyponatraemia 5/40 (12.5%) 0/4 (0%) 0/3 (0%) 1/9 (11.1%) 0/8 (0%) 0/2 (0%) 1/12 (8.3%) 7/41 (17.1%) 1/16 (6.3%) 2/18 (11.1%) 3/53 (5.7%) 10/60 (16.7%) 2/43 (4.7%)
    Hypophosphataemia 3/40 (7.5%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 1/8 (12.5%) 0/2 (0%) 0/12 (0%) 6/41 (14.6%) 0/16 (0%) 0/18 (0%) 2/53 (3.8%) 4/60 (6.7%) 1/43 (2.3%)
    Sodium retention 0/40 (0%) 1/4 (25%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 12/40 (30%) 1/4 (25%) 1/3 (33.3%) 0/9 (0%) 1/8 (12.5%) 0/2 (0%) 1/12 (8.3%) 2/41 (4.9%) 1/16 (6.3%) 2/18 (11.1%) 7/53 (13.2%) 11/60 (18.3%) 6/43 (14%)
    Back pain 9/40 (22.5%) 2/4 (50%) 1/3 (33.3%) 1/9 (11.1%) 1/8 (12.5%) 0/2 (0%) 0/12 (0%) 8/41 (19.5%) 1/16 (6.3%) 4/18 (22.2%) 6/53 (11.3%) 14/60 (23.3%) 8/43 (18.6%)
    Bone pain 2/40 (5%) 1/4 (25%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 1/53 (1.9%) 2/60 (3.3%) 1/43 (2.3%)
    Bursitis 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 1/12 (8.3%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Flank pain 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 1/12 (8.3%) 3/41 (7.3%) 1/16 (6.3%) 0/18 (0%) 2/53 (3.8%) 2/60 (3.3%) 2/43 (4.7%)
    Joint range of motion decreased 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 1/12 (8.3%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Limb discomfort 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 1/8 (12.5%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Muscle spasms 1/40 (2.5%) 0/4 (0%) 0/3 (0%) 1/9 (11.1%) 1/8 (12.5%) 0/2 (0%) 0/12 (0%) 1/41 (2.4%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 2/60 (3.3%) 1/43 (2.3%)
    Musculoskeletal chest pain 3/40 (7.5%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 1/8 (12.5%) 0/2 (0%) 0/12 (0%) 3/41 (7.3%) 1/16 (6.3%) 1/18 (5.6%) 3/53 (5.7%) 3/60 (5%) 1/43 (2.3%)
    Musculoskeletal pain 7/40 (17.5%) 0/4 (0%) 1/3 (33.3%) 1/9 (11.1%) 1/8 (12.5%) 0/2 (0%) 1/12 (8.3%) 6/41 (14.6%) 1/16 (6.3%) 2/18 (11.1%) 3/53 (5.7%) 4/60 (6.7%) 5/43 (11.6%)
    Musculoskeletal stiffness 2/40 (5%) 0/4 (0%) 0/3 (0%) 1/9 (11.1%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Myalgia 4/40 (10%) 0/4 (0%) 1/3 (33.3%) 0/9 (0%) 1/8 (12.5%) 0/2 (0%) 1/12 (8.3%) 2/41 (4.9%) 1/16 (6.3%) 0/18 (0%) 3/53 (5.7%) 3/60 (5%) 5/43 (11.6%)
    Neck pain 1/40 (2.5%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 1/12 (8.3%) 1/41 (2.4%) 1/16 (6.3%) 0/18 (0%) 5/53 (9.4%) 0/60 (0%) 0/43 (0%)
    Pain in extremity 7/40 (17.5%) 0/4 (0%) 1/3 (33.3%) 0/9 (0%) 1/8 (12.5%) 0/2 (0%) 1/12 (8.3%) 4/41 (9.8%) 0/16 (0%) 0/18 (0%) 6/53 (11.3%) 2/60 (3.3%) 3/43 (7%)
    Pain in jaw 0/40 (0%) 1/4 (25%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 1/43 (2.3%)
    Soft tissue swelling 0/40 (0%) 1/4 (25%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Spinal pain 2/40 (5%) 0/4 (0%) 0/3 (0%) 1/9 (11.1%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Nervous system disorders
    Balance disorder 1/40 (2.5%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 1/8 (12.5%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 1/43 (2.3%)
    Brain oedema 1/40 (2.5%) 1/4 (25%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 1/41 (2.4%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Dizziness 6/40 (15%) 0/4 (0%) 1/3 (33.3%) 1/9 (11.1%) 0/8 (0%) 0/2 (0%) 2/12 (16.7%) 7/41 (17.1%) 1/16 (6.3%) 3/18 (16.7%) 7/53 (13.2%) 9/60 (15%) 3/43 (7%)
    Dizziness postural 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 1/16 (6.3%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Dysgeusia 2/40 (5%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 2/8 (25%) 0/2 (0%) 0/12 (0%) 2/41 (4.9%) 0/16 (0%) 1/18 (5.6%) 6/53 (11.3%) 1/60 (1.7%) 2/43 (4.7%)
    Headache 11/40 (27.5%) 0/4 (0%) 1/3 (33.3%) 1/9 (11.1%) 3/8 (37.5%) 0/2 (0%) 2/12 (16.7%) 5/41 (12.2%) 2/16 (12.5%) 4/18 (22.2%) 8/53 (15.1%) 7/60 (11.7%) 8/43 (18.6%)
    Hemiparesis 1/40 (2.5%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 1/12 (8.3%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Hepatic encephalopathy 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 1/18 (5.6%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Hypoaesthesia 3/40 (7.5%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 1/41 (2.4%) 0/16 (0%) 0/18 (0%) 1/53 (1.9%) 1/60 (1.7%) 1/43 (2.3%)
    Neuropathy peripheral 2/40 (5%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 1/18 (5.6%) 2/53 (3.8%) 1/60 (1.7%) 0/43 (0%)
    Paraesthesia 1/40 (2.5%) 1/4 (25%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 1/12 (8.3%) 1/41 (2.4%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Peripheral motor neuropathy 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 2/41 (4.9%) 1/16 (6.3%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Peripheral sensory neuropathy 0/40 (0%) 0/4 (0%) 1/3 (33.3%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 3/41 (7.3%) 1/16 (6.3%) 2/18 (11.1%) 1/53 (1.9%) 1/60 (1.7%) 2/43 (4.7%)
    Sciatica 1/40 (2.5%) 1/4 (25%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 1/41 (2.4%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 2/60 (3.3%) 0/43 (0%)
    Taste disorder 1/40 (2.5%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 1/8 (12.5%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 2/60 (3.3%) 0/43 (0%)
    Psychiatric disorders
    Affect lability 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 1/12 (8.3%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Anxiety 6/40 (15%) 0/4 (0%) 0/3 (0%) 1/9 (11.1%) 2/8 (25%) 0/2 (0%) 0/12 (0%) 4/41 (9.8%) 0/16 (0%) 2/18 (11.1%) 9/53 (17%) 6/60 (10%) 2/43 (4.7%)
    Confusional state 3/40 (7.5%) 1/4 (25%) 0/3 (0%) 0/9 (0%) 1/8 (12.5%) 0/2 (0%) 1/12 (8.3%) 2/41 (4.9%) 0/16 (0%) 0/18 (0%) 1/53 (1.9%) 2/60 (3.3%) 2/43 (4.7%)
    Depression 2/40 (5%) 1/4 (25%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 1/41 (2.4%) 0/16 (0%) 0/18 (0%) 3/53 (5.7%) 5/60 (8.3%) 0/43 (0%)
    Insomnia 7/40 (17.5%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 1/8 (12.5%) 0/2 (0%) 1/12 (8.3%) 5/41 (12.2%) 0/16 (0%) 1/18 (5.6%) 5/53 (9.4%) 10/60 (16.7%) 5/43 (11.6%)
    Renal and urinary disorders
    Acute kidney injury 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 3/53 (5.7%) 2/60 (3.3%) 0/43 (0%)
    Dysuria 1/40 (2.5%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 1/18 (5.6%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Haematuria 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 1/8 (12.5%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 2/53 (3.8%) 1/60 (1.7%) 0/43 (0%)
    Leukocyturia 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 1/8 (12.5%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Nephrolithiasis 0/40 (0%) 0/4 (0%) 0/3 (0%) 1/9 (11.1%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Nocturia 1/40 (2.5%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 1/12 (8.3%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 1/60 (1.7%) 0/43 (0%)
    Renal failure 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 3/53 (5.7%) 0/60 (0%) 0/43 (0%)
    Urinary retention 1/40 (2.5%) 1/4 (25%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 1/43 (2.3%)
    Reproductive system and breast disorders
    Genital lesion 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 1/12 (8.3%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Respiratory, thoracic and mediastinal disorders
    Bronchospasm 0/40 (0%) 0/4 (0%) 0/3 (0%) 1/9 (11.1%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Cough 10/40 (25%) 1/4 (25%) 1/3 (33.3%) 2/9 (22.2%) 2/8 (25%) 0/2 (0%) 3/12 (25%) 5/41 (12.2%) 2/16 (12.5%) 6/18 (33.3%) 13/53 (24.5%) 15/60 (25%) 11/43 (25.6%)
    Dysphonia 2/40 (5%) 1/4 (25%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 1/41 (2.4%) 0/16 (0%) 3/18 (16.7%) 2/53 (3.8%) 1/60 (1.7%) 0/43 (0%)
    Dyspnoea 14/40 (35%) 3/4 (75%) 0/3 (0%) 2/9 (22.2%) 3/8 (37.5%) 1/2 (50%) 1/12 (8.3%) 7/41 (17.1%) 0/16 (0%) 6/18 (33.3%) 21/53 (39.6%) 20/60 (33.3%) 6/43 (14%)
    Dyspnoea exertional 2/40 (5%) 1/4 (25%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 1/12 (8.3%) 3/41 (7.3%) 2/16 (12.5%) 0/18 (0%) 4/53 (7.5%) 3/60 (5%) 1/43 (2.3%)
    Epistaxis 1/40 (2.5%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 3/53 (5.7%) 0/60 (0%) 1/43 (2.3%)
    Haemoptysis 5/40 (12.5%) 1/4 (25%) 0/3 (0%) 1/9 (11.1%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 5/41 (12.2%) 0/16 (0%) 1/18 (5.6%) 2/53 (3.8%) 3/60 (5%) 2/43 (4.7%)
    Hiccups 1/40 (2.5%) 1/4 (25%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 2/41 (4.9%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 1/43 (2.3%)
    Hypoxia 1/40 (2.5%) 1/4 (25%) 0/3 (0%) 1/9 (11.1%) 2/8 (25%) 0/2 (0%) 0/12 (0%) 1/41 (2.4%) 0/16 (0%) 2/18 (11.1%) 2/53 (3.8%) 4/60 (6.7%) 1/43 (2.3%)
    Nasal congestion 1/40 (2.5%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 1/18 (5.6%) 2/53 (3.8%) 4/60 (6.7%) 1/43 (2.3%)
    Oropharyngeal pain 0/40 (0%) 0/4 (0%) 1/3 (33.3%) 2/9 (22.2%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 1/18 (5.6%) 1/53 (1.9%) 3/60 (5%) 0/43 (0%)
    Paranasal sinus discomfort 0/40 (0%) 0/4 (0%) 0/3 (0%) 1/9 (11.1%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Pleural effusion 2/40 (5%) 2/4 (50%) 0/3 (0%) 0/9 (0%) 1/8 (12.5%) 0/2 (0%) 0/12 (0%) 10/41 (24.4%) 1/16 (6.3%) 0/18 (0%) 7/53 (13.2%) 4/60 (6.7%) 3/43 (7%)
    Pneumonia aspiration 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 1/16 (6.3%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Pneumonitis 1/40 (2.5%) 0/4 (0%) 1/3 (33.3%) 0/9 (0%) 0/8 (0%) 1/2 (50%) 1/12 (8.3%) 1/41 (2.4%) 0/16 (0%) 0/18 (0%) 2/53 (3.8%) 2/60 (3.3%) 2/43 (4.7%)
    Pneumothorax 1/40 (2.5%) 0/4 (0%) 1/3 (33.3%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 1/41 (2.4%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Productive cough 7/40 (17.5%) 1/4 (25%) 0/3 (0%) 0/9 (0%) 1/8 (12.5%) 0/2 (0%) 0/12 (0%) 2/41 (4.9%) 0/16 (0%) 2/18 (11.1%) 7/53 (13.2%) 5/60 (8.3%) 2/43 (4.7%)
    Pulmonary embolism 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 1/12 (8.3%) 1/41 (2.4%) 1/16 (6.3%) 0/18 (0%) 1/53 (1.9%) 2/60 (3.3%) 0/43 (0%)
    Pulmonary oedema 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 1/18 (5.6%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Respiratory tract congestion 0/40 (0%) 1/4 (25%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 1/41 (2.4%) 0/16 (0%) 0/18 (0%) 1/53 (1.9%) 0/60 (0%) 0/43 (0%)
    Rhinorrhoea 0/40 (0%) 1/4 (25%) 0/3 (0%) 0/9 (0%) 1/8 (12.5%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 1/18 (5.6%) 1/53 (1.9%) 1/60 (1.7%) 0/43 (0%)
    Sinus congestion 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 1/18 (5.6%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Upper-airway cough syndrome 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 1/41 (2.4%) 1/16 (6.3%) 3/18 (16.7%) 0/53 (0%) 0/60 (0%) 1/43 (2.3%)
    Wheezing 0/40 (0%) 0/4 (0%) 1/3 (33.3%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 1/12 (8.3%) 0/41 (0%) 0/16 (0%) 3/18 (16.7%) 0/53 (0%) 1/60 (1.7%) 2/43 (4.7%)
    Skin and subcutaneous tissue disorders
    Alopecia 0/40 (0%) 1/4 (25%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 1/41 (2.4%) 1/16 (6.3%) 1/18 (5.6%) 4/53 (7.5%) 2/60 (3.3%) 3/43 (7%)
    Dermatitis 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 1/12 (8.3%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Dry skin 4/40 (10%) 1/4 (25%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 2/12 (16.7%) 3/41 (7.3%) 1/16 (6.3%) 2/18 (11.1%) 2/53 (3.8%) 4/60 (6.7%) 3/43 (7%)
    Hair growth abnormal 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 1/18 (5.6%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Hyperhidrosis 2/40 (5%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 1/41 (2.4%) 0/16 (0%) 0/18 (0%) 1/53 (1.9%) 1/60 (1.7%) 3/43 (7%)
    Night sweats 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 1/41 (2.4%) 1/16 (6.3%) 1/18 (5.6%) 0/53 (0%) 2/60 (3.3%) 0/43 (0%)
    Photosensitivity reaction 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 1/12 (8.3%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Pruritus 6/40 (15%) 1/4 (25%) 1/3 (33.3%) 2/9 (22.2%) 1/8 (12.5%) 0/2 (0%) 2/12 (16.7%) 4/41 (9.8%) 1/16 (6.3%) 3/18 (16.7%) 5/53 (9.4%) 16/60 (26.7%) 3/43 (7%)
    Rash 5/40 (12.5%) 1/4 (25%) 2/3 (66.7%) 0/9 (0%) 2/8 (25%) 0/2 (0%) 0/12 (0%) 7/41 (17.1%) 3/16 (18.8%) 3/18 (16.7%) 7/53 (13.2%) 10/60 (16.7%) 3/43 (7%)
    Rash maculo-papular 2/40 (5%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 1/8 (12.5%) 0/2 (0%) 1/12 (8.3%) 0/41 (0%) 0/16 (0%) 2/18 (11.1%) 1/53 (1.9%) 6/60 (10%) 2/43 (4.7%)
    Rash pruritic 1/40 (2.5%) 1/4 (25%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 1/41 (2.4%) 1/16 (6.3%) 1/18 (5.6%) 2/53 (3.8%) 1/60 (1.7%) 0/43 (0%)
    Skin burning sensation 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 1/12 (8.3%) 0/41 (0%) 0/16 (0%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Skin hypopigmentation 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 0/41 (0%) 0/16 (0%) 1/18 (5.6%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Vascular disorders
    Deep vein thrombosis 2/40 (5%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 1/41 (2.4%) 1/16 (6.3%) 0/18 (0%) 0/53 (0%) 0/60 (0%) 0/43 (0%)
    Hot flush 0/40 (0%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 1/41 (2.4%) 0/16 (0%) 1/18 (5.6%) 1/53 (1.9%) 0/60 (0%) 1/43 (2.3%)
    Hypertension 2/40 (5%) 0/4 (0%) 0/3 (0%) 0/9 (0%) 0/8 (0%) 0/2 (0%) 0/12 (0%) 3/41 (7.3%) 0/16 (0%) 0/18 (0%) 3/53 (5.7%) 5/60 (8.3%) 6/43 (14%)
    Hypotension 2/40 (5%) 0/4 (0%) 0/3 (0%) 1/9 (11.1%) 0/8 (0%) 0/2 (0%) 2/12 (16.7%) 1/41 (2.4%) 0/16 (0%) 2/18 (11.1%) 1/53 (1.9%) 2/60 (3.3%) 2/43 (4.7%)

    Limitations/Caveats

    This study was terminated early by sponsor for reasons unrelated to safety.

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.

    Results Point of Contact

    Name/Title Bristol-Myers Squibb Study Director
    Organization Bristol-Myers Squibb
    Phone Please email
    Email Clinical.Trials@bms.com
    Responsible Party:
    Bristol-Myers Squibb
    ClinicalTrials.gov Identifier:
    NCT02750514
    Other Study ID Numbers:
    • CA018-001
    First Posted:
    Apr 25, 2016
    Last Update Posted:
    Mar 22, 2021
    Last Verified:
    Feb 1, 2021