Clincosm LogoSign in Get a demo

A Study of Nivolumab Safety and Pharmacokinetics in Patients With Severe Sepsis or Septic Shock.

Sponsor
Bristol-Myers Squibb (Industry)
Overall Status
Completed
CT.gov ID
NCT02960854
Collaborator
(none)
38
Enrollment
16
Locations
2
Arms
12.9
Actual Duration (Months)
2.4
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

A study to evaluate the safety, tolerability and pharmacokinetics of Nivolumab in participants with severe sepsis or septic shock.

Condition or Disease Intervention/Treatment Phase
  • Biological: Nivolumab
 Phase 1

Study Design

Study Type:
Interventional
Actual Enrollment :
38 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Other
Official Title:
Randomized, Double-Blind, Parallel Group Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of BMS-936558 (Nivolumab) in Participants With Severe Sepsis or Septic Shock.
Actual Study Start Date :
Dec 7, 2016
Actual Primary Completion Date :
Jan 5, 2018
Actual Study Completion Date :
Jan 5, 2018

Arms and Interventions

Arm Intervention/Treatment
Experimental: Nivolumab 1

Dose 1

Biological: Nivolumab
Specified dose on specified days
Other Names:
  • BMS-936558

    		•
    Experimental: Nivolumab 2

    Dose 2

    Biological: Nivolumab
    Specified dose on specified days
    Other Names:
  • BMS-936558

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Percentage of Incidence Rates of Serious Adverse Events (SAEs), Adverse Events (AEs), Immune-mediated AEs, AEs Leading to Discontinuation, and Deaths [Screening, day -1, day 1 and subsequent days after, up to 90 days]

    2. Composite of Vital Signs and Electrocardiogram (ECG) [Screening up to 90 days (Discharge)]

      Includes body temperature, respiratory rate, blood pressure and heart rate. Blood pressure and heart rate should be measured after the participant has been resting quietly for at least 5 minutes.

    3. Peak Nivolumab Serum Concentration (Cmax) [Day 1 and subsequent days after, up to 90 days]

      Participants peak nivolumab serum concentration

    4. Trough Nivolumab Serum Concentration (Cmin) [Day 1 and subsequent days after, up to 90 days]

      Participant trough nivolumab serum concentration

    5. Average Nivolumab Serum Concentration (Cavg) [Day 1 and subsequent days after, up to 90 days]

      Participant average nivolumab serum concentration

    6. Time of Maximum Observed Concentration (Tmax) [Day 1 and subsequent days after, up to 90 days]

      Participant observed time of maximum concentration

    7. Area Under the Serum Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration [AUC(0-T)] [Day 1 and subsequent days after, up to 90 days]

      Area under the serum concentration-time curve from time zero to time of last quantifiable concentration

    8. Total Clearance (CLT) [Day 1 and subsequent days after, up to 90 days]

      Total clearance of serum concentration of nivolumab

    9. Volume of Distribution (Vd) [Day 1 and subsequent days after, up to 90 days]

      Vlume of distribution of nivolumab serum concentration

    10. Half-life (T1/2) [Day 1 and subsequent days after, up to 90 days]

      Half-Life of nivolumab derived from serum concentration

    Secondary Outcome Measures

    1. Receptor Occupancy [Day 1 and up to day 90 (discharge)]

      Receptor occupancy on T cells at baseline and after study treatment administration at planned sampling time points

    2. Number of Participants With Detectable Anti-nivolumab Antibodies [Baseline and subsequent days after, up to 90 days]

      Participant with positive anti-drug antibody detection

    3. Number of Participants With Any Detectable Anti-drug Antibodies [Baseline and subsequent days after, up to 90 days]

    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:

    • Men and women ages ≥ 18 years old

    • Documented or suspected infection

    • Severe sepsis or septic shock for at least 24 hours

    • Sepsis-induced immunosuppression

    • In Intensive Care Unit (ICU) with no plans to discharge in next 24 hours

    Exclusion Criteria:

    • Previous episode of severe sepsis or septic shock with ICU admission during the current hospitalization

    • Autoimmune disease

    • Organ or bone marrow transplant

    • Cancer treatment in the past 6 weeks

    • Human immunodeficiency virus (HIV) infection and not on therapy prior to this episode of sepsis; hepatitis C virus(HCV) infection and still has virus (not cured); Chronic hepatitis B virus (HBV) infection and not on treatment

    Other protocol defined inclusion/exclusion criteria could apply

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Uc Davis Medical Center Sacramento California United States 95817
    2 Univ. Of Colorado Health Colorado Springs Colorado United States 80909
    3 Denver Health Medical Center Denver Colorado United States 80204
    4 University Of Florida Gainesville Florida United States 32610
    5 Pulmonary And Critical Care Of Atlanta Atlanta Georgia United States 30303
    6 Osf Saint Francis Medical Center Peoria Illinois United States 61637
    7 University Of Kentucky Lexington Kentucky United States 40536
    8 Massachusetts General Hospital Boston Massachusetts United States 02114
    9 Beth Israel Deaconess Medical Center (BIDMC) Boston Massachusetts United States 02215
    10 Baystate Medical Center Springfield Massachusetts United States 01199
    11 University of Michigan, Division of Acute Care Surgery Ann Arbor Michigan United States 48109-5008
    12 Washington University School Of Medicine Saint Louis Missouri United States 63110
    13 Duke University Medical Center Durham North Carolina United States 27710
    14 The Ohio State University Columbus Ohio United States 43210
    15 UPMC Pittsburgh Pennsylvania United States 15261-2500
    16 Harborview Medical Center Seattle Washington United States 98104

    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:
    NCT02960854
    Other Study ID Numbers:
    • CA209-923
    First Posted:
    Nov 10, 2016
    Last Update Posted:
    Apr 23, 2019
    Last Verified:
    Apr 1, 2019
    Additional relevant MeSH terms:
    Sepsis
    Toxemia
    Nivolumab

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail 38 subjects were enrolled in the study. 31 were randomized; 7 not randomized: (5) Failed to meet study eligibility criteria, (1) died, (1) withdrew consent
    Arm/Group Title Nivolumab (480 mg) Nivolumab (960 mg)
    Arm/Group Description the assessment of the safety and tolerability of a single dose of nivolumab 480 mg the assessment of the safety and tolerability of a single dose of nivolumab 960 mg
    Period Title: Overall Study
    STARTED 15 16
    COMPLETED 8 7
    NOT COMPLETED 7 9

    Baseline Characteristics

    Arm/Group Title Nivolumab (480 mg) Nivolumab (960 mg) Total
    Arm/Group Description the assessment of the safety and tolerability of a single dose of nivolumab 480 mg the assessment of the safety and tolerability of a single dose of nivolumab 960 mg Total of all reporting groups
    Overall Participants 15 16 31
    Age (Years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Years]
    56.6
    (12.30)
    58.4
    (15.16)
    57.5
    (13.65)
    Sex: Female, Male (Count of Participants)
    Female
    4
    26.7%
    6
    37.5%
    10
    32.3%
    Male
    11
    73.3%
    10
    62.5%
    21
    67.7%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    2
    13.3%
    1
    6.3%
    3
    9.7%
    Not Hispanic or Latino
    13
    86.7%
    15
    93.8%
    28
    90.3%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    Asian
    0
    0%
    0
    0%
    0
    0%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    2
    13.3%
    4
    25%
    6
    19.4%
    White
    12
    80%
    11
    68.8%
    23
    74.2%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    1
    6.7%
    1
    6.3%
    2
    6.5%

    Outcome Measures

    1. Primary Outcome
    Title Percentage of Incidence Rates of Serious Adverse Events (SAEs), Adverse Events (AEs), Immune-mediated AEs, AEs Leading to Discontinuation, and Deaths
    Description
    Time Frame Screening, day -1, day 1 and subsequent days after, up to 90 days

    Outcome Measure Data

    Analysis Population Description
    All treated participants
    Arm/Group Title Nivolumab (480 mg) Nivolumab (960 mg)
    Arm/Group Description the assessment of the safety and tolerability of a single dose of nivolumab 480 mg the assessment of the safety and tolerability of a single dose of nivolumab 960 mg
    Measure Participants 15 16
    Serious Adverse Events (SAEs)
    6.7
    43.8
    Adverse Events (AEs)
    93.3
    87.5
    Immune-Mediated Adverse Events
    53.3
    81.3
    AEs leading to discontinuation
    0.0
    0.0
    Deaths
    40.0
    38.7
    2. Primary Outcome
    Title Composite of Vital Signs and Electrocardiogram (ECG)
    Description Includes body temperature, respiratory rate, blood pressure and heart rate. Blood pressure and heart rate should be measured after the participant has been resting quietly for at least 5 minutes.
    Time Frame Screening up to 90 days (Discharge)

    Outcome Measure Data

    Analysis Population Description
    All treated participants
    Arm/Group Title Nivolumab (480 mg) Nivolumab (960 mg)
    Arm/Group Description the assessment of the safety and tolerability of a single dose of nivolumab 480 mg the assessment of the safety and tolerability of a single dose of nivolumab 960 mg
    Measure Participants 15 16
    ECG Change from Baseline (Discharge)
    -18.0
    (31.68)
    -29.0
    (3.46)
    Vital Signs - Diastolic Pressure (mmHg) Screening
    61.5
    (20.37)
    58.5
    (9.00)
    Vital Signs - Systolic Pressure (mmHg) Screening
    116.5
    (21.48)
    105.5
    (14.65)
    Vital Signs - Heart Rate (beats/min) Screening
    80.1
    (21.34)
    94.6
    (16.64)
    Vital Signs - Resp. Rate (breaths/min) Screening
    23.0
    (6.08)
    24.4
    (8.83)
    Vital Signs - Temperature (C) Screening
    37.19
    (0.79)
    37.11
    (0.77)
    Vital Signs - Diastolic Pressure (mmHg) Discharge
    79.7
    (16.49)
    70.5
    (16.28)
    Vital Signs - Systolic Pressure (mmHg) Discharge
    129.0
    (25.06)
    110.0
    (16.47)
    Vital Signs - Heart Rate (beats/min) Discharge
    85.3
    (18.89)
    86.5
    (19.76)
    Vital Signs - Resp. Rate (breaths/min) Discharge
    18.8
    (2.71)
    17.5
    (3.32)
    Vital Signs - Temperature (C) Discharge
    36.60
    (0.276)
    36.90
    (0.337)
    3. Primary Outcome
    Title Peak Nivolumab Serum Concentration (Cmax)
    Description Participants peak nivolumab serum concentration
    Time Frame Day 1 and subsequent days after, up to 90 days

    Outcome Measure Data

    Analysis Population Description
    All Treated participants
    Arm/Group Title Nivolumab (480 mg) Nivolumab (960 mg)
    Arm/Group Description the assessment of the safety and tolerability of a single dose of nivolumab 480 mg the assessment of the safety and tolerability of a single dose of nivolumab 960 mg
    Measure Participants 15 16
    Geometric Mean (Geometric Coefficient of Variation) [ug/mL]
    123
    (85.4)
    246
    (85.4)
    4. Primary Outcome
    Title Trough Nivolumab Serum Concentration (Cmin)
    Description Participant trough nivolumab serum concentration
    Time Frame Day 1 and subsequent days after, up to 90 days

    Outcome Measure Data

    Analysis Population Description
    All treated participants
    Arm/Group Title Nivolumab (480 mg) Nivolumab (960 mg)
    Arm/Group Description the assessment of the safety and tolerability of a single dose of nivolumab 480 mg the assessment of the safety and tolerability of a single dose of nivolumab 960 mg
    Measure Participants 15 16
    Geometric Mean (Geometric Coefficient of Variation) [ug/mL]
    21.6
    (39)
    43.2
    (39)
    5. Primary Outcome
    Title Average Nivolumab Serum Concentration (Cavg)
    Description Participant average nivolumab serum concentration
    Time Frame Day 1 and subsequent days after, up to 90 days

    Outcome Measure Data

    Analysis Population Description
    All treated participants
    Arm/Group Title Nivolumab (480 mg) Nivolumab (960 mg)
    Arm/Group Description the assessment of the safety and tolerability of a single dose of nivolumab 480 mg the assessment of the safety and tolerability of a single dose of nivolumab 960 mg
    Measure Participants 15 16
    Geometric Mean (Geometric Coefficient of Variation) [ug/mL]
    42.7
    (28.5)
    85.4
    (28.5)
    6. Primary Outcome
    Title Time of Maximum Observed Concentration (Tmax)
    Description Participant observed time of maximum concentration
    Time Frame Day 1 and subsequent days after, up to 90 days

    Outcome Measure Data

    Analysis Population Description
    All Treated participants
    Arm/Group Title Nivolumab (480 mg) Nivolumab (960 mg)
    Arm/Group Description the assessment of the safety and tolerability of a single dose of nivolumab 480 mg the assessment of the safety and tolerability of a single dose of nivolumab 960 mg
    Measure Participants 15 16
    Median (Full Range) [hours]
    1.67
    1.53
    7. Primary Outcome
    Title Area Under the Serum Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration [AUC(0-T)]
    Description Area under the serum concentration-time curve from time zero to time of last quantifiable concentration
    Time Frame Day 1 and subsequent days after, up to 90 days

    Outcome Measure Data

    Analysis Population Description
    All Treated Participants
    Arm/Group Title Nivolumab (480 mg) Nivolumab (960 mg)
    Arm/Group Description the assessment of the safety and tolerability of a single dose of nivolumab 480 mg the assessment of the safety and tolerability of a single dose of nivolumab 960 mg
    Measure Participants 15 16
    Geometric Mean (Geometric Coefficient of Variation) [h*ug/mL]
    18099
    (51)
    32130
    (83)
    8. Primary Outcome
    Title Total Clearance (CLT)
    Description Total clearance of serum concentration of nivolumab
    Time Frame Day 1 and subsequent days after, up to 90 days

    Outcome Measure Data

    Analysis Population Description
    All Treated Participants
    Arm/Group Title Nivolumab (480 mg) Nivolumab (960 mg)
    Arm/Group Description the assessment of the safety and tolerability of a single dose of nivolumab 480 mg the assessment of the safety and tolerability of a single dose of nivolumab 960 mg
    Measure Participants 15 16
    Geometric Mean (Geometric Coefficient of Variation) [L/h]
    0.025
    (50)
    0.027
    (85)
    9. Primary Outcome
    Title Volume of Distribution (Vd)
    Description Vlume of distribution of nivolumab serum concentration
    Time Frame Day 1 and subsequent days after, up to 90 days

    Outcome Measure Data

    Analysis Population Description
    All Treated Participants
    Arm/Group Title Nivolumab (480 mg) Nivolumab (960 mg)
    Arm/Group Description the assessment of the safety and tolerability of a single dose of nivolumab 480 mg the assessment of the safety and tolerability of a single dose of nivolumab 960 mg
    Measure Participants 15 16
    Geometric Mean (Geometric Coefficient of Variation) [L]
    12.0
    (42)
    13.3
    (54)
    10. Primary Outcome
    Title Half-life (T1/2)
    Description Half-Life of nivolumab derived from serum concentration
    Time Frame Day 1 and subsequent days after, up to 90 days

    Outcome Measure Data

    Analysis Population Description
    All Treated Participants
    Arm/Group Title Nivolumab (480 mg) Nivolumab (960 mg)
    Arm/Group Description the assessment of the safety and tolerability of a single dose of nivolumab 480 mg the assessment of the safety and tolerability of a single dose of nivolumab 960 mg
    Measure Participants 15 16
    Mean (Standard Deviation) [hours]
    353
    (126.5)
    378
    (189.6)
    11. Secondary Outcome
    Title Receptor Occupancy
    Description Receptor occupancy on T cells at baseline and after study treatment administration at planned sampling time points
    Time Frame Day 1 and up to day 90 (discharge)

    Outcome Measure Data

    Analysis Population Description
    All Treated Participants
    Arm/Group Title Nivolumab (480 mg) Nivolumab (960 mg)
    Arm/Group Description the assessment of the safety and tolerability of a single dose of nivolumab 480 mg the assessment of the safety and tolerability of a single dose of nivolumab 960 mg
    Measure Participants 15 16
    Baseline
    0.00
    (0.00)
    0.00
    (0.00)
    Study Discharge
    81.272
    (27.69)
    71.14
    (34.83)
    12. Secondary Outcome
    Title Number of Participants With Detectable Anti-nivolumab Antibodies
    Description Participant with positive anti-drug antibody detection
    Time Frame Baseline and subsequent days after, up to 90 days

    Outcome Measure Data

    Analysis Population Description
    All Treated Participants
    Arm/Group Title Nivolumab (480 mg) Nivolumab (960 mg)
    Arm/Group Description the assessment of the safety and tolerability of a single dose of nivolumab 480 mg the assessment of the safety and tolerability of a single dose of nivolumab 960 mg
    Measure Participants 15 16
    Number [Percentage]
    73.3
    75.0
    13. Secondary Outcome
    Title Number of Participants With Any Detectable Anti-drug Antibodies
    Description
    Time Frame Baseline and subsequent days after, up to 90 days

    Outcome Measure Data

    Analysis Population Description
    All Treated Participants
    Arm/Group Title Nivolumab (480 mg) Nivolumab (960 mg)
    Arm/Group Description the assessment of the safety and tolerability of a single dose of nivolumab 480 mg the assessment of the safety and tolerability of a single dose of nivolumab 960 mg
    Measure Participants 15 16
    Number [Percentage]
    26.7
    56.3

    Adverse Events

    Time Frame Adverse events (AEs) and serious adverse events (SAEs) were collected from Day 1 following single dose of nivolumab, up until Day 90.
    Adverse Event Reporting Description
    Arm/Group Title NIVOLUMAB 480mg NIVOLUMAB 960mg
    Arm/Group Description the assessment of the safety and tolerability of a single dose of nivolumab 480 mg the assessment of the safety and tolerability of a single dose of nivolumab 960 mg
    All Cause Mortality
    NIVOLUMAB 480mg NIVOLUMAB 960mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 4/15 (26.7%) 6/16 (37.5%)
    Serious Adverse Events
    NIVOLUMAB 480mg NIVOLUMAB 960mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 1/15 (6.7%) 7/16 (43.8%)
    Blood and lymphatic system disorders
    Anaemia 0/15 (0%) 2/16 (12.5%)
    Disseminated intravascular coagulation 0/15 (0%) 1/16 (6.3%)
    Thrombocytopenia 0/15 (0%) 1/16 (6.3%)
    Cardiac disorders
    Cardiac arrest 0/15 (0%) 1/16 (6.3%)
    Gastrointestinal disorders
    Gastrointestinal haemorrhage 0/15 (0%) 1/16 (6.3%)
    Intra-abdominal haemorrhage 1/15 (6.7%) 0/16 (0%)
    Megacolon 0/15 (0%) 1/16 (6.3%)
    General disorders
    Multiple organ dysfunction syndrome 0/15 (0%) 1/16 (6.3%)
    Infections and infestations
    Abdominal abscess 1/15 (6.7%) 0/16 (0%)
    Urosepsis 0/15 (0%) 1/16 (6.3%)
    Investigations
    Electrocardiogram st segment elevation 0/15 (0%) 1/16 (6.3%)
    Metabolism and nutrition disorders
    Acidosis 0/15 (0%) 1/16 (6.3%)
    Renal and urinary disorders
    Acute kidney injury 0/15 (0%) 1/16 (6.3%)
    Ureterolithiasis 0/15 (0%) 1/16 (6.3%)
    Other (Not Including Serious) Adverse Events
    NIVOLUMAB 480mg NIVOLUMAB 960mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 14/15 (93.3%) 14/16 (87.5%)
    Blood and lymphatic system disorders
    Anaemia 6/15 (40%) 8/16 (50%)
    Bandaemia 0/15 (0%) 1/16 (6.3%)
    Coagulopathy 1/15 (6.7%) 1/16 (6.3%)
    Disseminated intravascular coagulation 0/15 (0%) 1/16 (6.3%)
    Eosinophilia 0/15 (0%) 1/16 (6.3%)
    Leukocytosis 2/15 (13.3%) 4/16 (25%)
    Lymphadenopathy mediastinal 0/15 (0%) 1/16 (6.3%)
    Thrombocytopenia 0/15 (0%) 2/16 (12.5%)
    Cardiac disorders
    Atrial fibrillation 2/15 (13.3%) 1/16 (6.3%)
    Bradycardia 0/15 (0%) 2/16 (12.5%)
    Bundle branch block right 0/15 (0%) 1/16 (6.3%)
    Cardiac arrest 1/15 (6.7%) 0/16 (0%)
    Cardiac failure 0/15 (0%) 2/16 (12.5%)
    Cardiomegaly 0/15 (0%) 1/16 (6.3%)
    Sinus bradycardia 1/15 (6.7%) 0/16 (0%)
    Sinus node dysfunction 0/15 (0%) 1/16 (6.3%)
    Sinus tachycardia 0/15 (0%) 2/16 (12.5%)
    Supraventricular tachycardia 0/15 (0%) 2/16 (12.5%)
    Tachycardia 1/15 (6.7%) 2/16 (12.5%)
    Ventricular extrasystoles 0/15 (0%) 1/16 (6.3%)
    Ear and labyrinth disorders
    Mastoid effusion 0/15 (0%) 1/16 (6.3%)
    Endocrine disorders
    Hypothyroidism 1/15 (6.7%) 1/16 (6.3%)
    Eye disorders
    Corneal epithelium defect 0/15 (0%) 1/16 (6.3%)
    Macular degeneration 0/15 (0%) 1/16 (6.3%)
    Periorbital oedema 0/15 (0%) 1/16 (6.3%)
    Pupils unequal 0/15 (0%) 1/16 (6.3%)
    Gastrointestinal disorders
    Abdominal distension 0/15 (0%) 1/16 (6.3%)
    Abdominal pain 1/15 (6.7%) 0/16 (0%)
    Diarrhoea 5/15 (33.3%) 2/16 (12.5%)
    Dyspepsia 0/15 (0%) 1/16 (6.3%)
    Dysphagia 2/15 (13.3%) 3/16 (18.8%)
    Flatulence 1/15 (6.7%) 0/16 (0%)
    Gastrointestinal fistula 1/15 (6.7%) 0/16 (0%)
    Gastrointestinal haemorrhage 1/15 (6.7%) 0/16 (0%)
    Gastrointestinal wall thickening 0/15 (0%) 1/16 (6.3%)
    Haematochezia 0/15 (0%) 1/16 (6.3%)
    Ileus 1/15 (6.7%) 0/16 (0%)
    Impaired gastric emptying 0/15 (0%) 1/16 (6.3%)
    Inguinal hernia 1/15 (6.7%) 0/16 (0%)
    Intra-abdominal fluid collection 1/15 (6.7%) 0/16 (0%)
    Melaena 0/15 (0%) 1/16 (6.3%)
    Nausea 4/15 (26.7%) 2/16 (12.5%)
    Pancreatitis 1/15 (6.7%) 0/16 (0%)
    Rectal haemorrhage 1/15 (6.7%) 0/16 (0%)
    Salivary hypersecretion 0/15 (0%) 1/16 (6.3%)
    Swollen tongue 0/15 (0%) 1/16 (6.3%)
    Upper gastrointestinal haemorrhage 1/15 (6.7%) 0/16 (0%)
    Vomiting 3/15 (20%) 2/16 (12.5%)
    General disorders
    Asthenia 1/15 (6.7%) 0/16 (0%)
    Catheter site haematoma 1/15 (6.7%) 0/16 (0%)
    Catheter site haemorrhage 1/15 (6.7%) 0/16 (0%)
    Chest pain 1/15 (6.7%) 0/16 (0%)
    Face oedema 0/15 (0%) 1/16 (6.3%)
    Fatigue 1/15 (6.7%) 1/16 (6.3%)
    Generalised oedema 0/15 (0%) 1/16 (6.3%)
    Oedema 1/15 (6.7%) 0/16 (0%)
    Oedema peripheral 2/15 (13.3%) 2/16 (12.5%)
    Pain 1/15 (6.7%) 0/16 (0%)
    Peripheral swelling 1/15 (6.7%) 0/16 (0%)
    Pyrexia 5/15 (33.3%) 6/16 (37.5%)
    Secretion discharge 0/15 (0%) 1/16 (6.3%)
    Hepatobiliary disorders
    Cholecystitis 1/15 (6.7%) 1/16 (6.3%)
    Cholelithiasis 2/15 (13.3%) 1/16 (6.3%)
    Hepatic cirrhosis 1/15 (6.7%) 0/16 (0%)
    Hepatic lesion 0/15 (0%) 1/16 (6.3%)
    Hepatic steatosis 1/15 (6.7%) 1/16 (6.3%)
    Hepatitis 1/15 (6.7%) 0/16 (0%)
    Hepatomegaly 1/15 (6.7%) 0/16 (0%)
    Hyperbilirubinaemia 0/15 (0%) 2/16 (12.5%)
    Porcelain gallbladder 1/15 (6.7%) 0/16 (0%)
    Infections and infestations
    Abdominal infection 1/15 (6.7%) 1/16 (6.3%)
    Candida infection 0/15 (0%) 2/16 (12.5%)
    Cellulitis 1/15 (6.7%) 1/16 (6.3%)
    Conjunctivitis 1/15 (6.7%) 0/16 (0%)
    Genital infection fungal 1/15 (6.7%) 0/16 (0%)
    Herpes dermatitis 1/15 (6.7%) 0/16 (0%)
    Herpes simplex 1/15 (6.7%) 0/16 (0%)
    Impetigo 0/15 (0%) 1/16 (6.3%)
    Lung infection 0/15 (0%) 1/16 (6.3%)
    Oral candidiasis 1/15 (6.7%) 0/16 (0%)
    Oral herpes 1/15 (6.7%) 0/16 (0%)
    Osteomyelitis 1/15 (6.7%) 0/16 (0%)
    Pneumonia 0/15 (0%) 1/16 (6.3%)
    Purulent discharge 1/15 (6.7%) 0/16 (0%)
    Staphylococcal infection 0/15 (0%) 2/16 (12.5%)
    Subcutaneous abscess 0/15 (0%) 1/16 (6.3%)
    Tracheitis 0/15 (0%) 2/16 (12.5%)
    Urinary tract infection 1/15 (6.7%) 1/16 (6.3%)
    Urinary tract infection bacterial 1/15 (6.7%) 0/16 (0%)
    Viral tracheitis 1/15 (6.7%) 0/16 (0%)
    Viral upper respiratory tract infection 1/15 (6.7%) 0/16 (0%)
    Wound infection 0/15 (0%) 1/16 (6.3%)
    Injury, poisoning and procedural complications
    Craniocerebral injury 0/15 (0%) 1/16 (6.3%)
    Excoriation 1/15 (6.7%) 0/16 (0%)
    Foreign body 0/15 (0%) 1/16 (6.3%)
    Limb injury 1/15 (6.7%) 0/16 (0%)
    Procedural haemorrhage 1/15 (6.7%) 0/16 (0%)
    Stoma site discharge 1/15 (6.7%) 0/16 (0%)
    Subcutaneous haematoma 1/15 (6.7%) 0/16 (0%)
    Wound dehiscence 0/15 (0%) 1/16 (6.3%)
    Investigations
    Activated partial thromboplastin time prolonged 0/15 (0%) 1/16 (6.3%)
    Alanine aminotransferase abnormal 1/15 (6.7%) 0/16 (0%)
    Alanine aminotransferase increased 0/15 (0%) 2/16 (12.5%)
    Ammonia increased 1/15 (6.7%) 0/16 (0%)
    Amylase increased 0/15 (0%) 1/16 (6.3%)
    Aspartate aminotransferase abnormal 1/15 (6.7%) 0/16 (0%)
    Aspartate aminotransferase increased 0/15 (0%) 2/16 (12.5%)
    Bacterial test positive 1/15 (6.7%) 2/16 (12.5%)
    Blood alkaline phosphatase increased 1/15 (6.7%) 2/16 (12.5%)
    Blood bilirubin abnormal 1/15 (6.7%) 1/16 (6.3%)
    Blood bilirubin increased 1/15 (6.7%) 2/16 (12.5%)
    Blood creatinine increased 2/15 (13.3%) 1/16 (6.3%)
    Blood glucose increased 1/15 (6.7%) 0/16 (0%)
    Blood lactate dehydrogenase increased 0/15 (0%) 1/16 (6.3%)
    Blood potassium increased 0/15 (0%) 1/16 (6.3%)
    Blood pressure increased 0/15 (0%) 1/16 (6.3%)
    Brain natriuretic peptide increased 0/15 (0%) 1/16 (6.3%)
    Breath sounds abnormal 1/15 (6.7%) 1/16 (6.3%)
    Bronchoalveolar lavage abnormal 0/15 (0%) 1/16 (6.3%)
    C-reactive protein increased 0/15 (0%) 1/16 (6.3%)
    Chest x-ray abnormal 1/15 (6.7%) 1/16 (6.3%)
    Clostridium test positive 0/15 (0%) 1/16 (6.3%)
    Ejection fraction decreased 0/15 (0%) 1/16 (6.3%)
    Electrocardiogram qt prolonged 1/15 (6.7%) 1/16 (6.3%)
    Fungal test positive 0/15 (0%) 1/16 (6.3%)
    Gastric ph increased 0/15 (0%) 1/16 (6.3%)
    Glycosylated haemoglobin increased 0/15 (0%) 1/16 (6.3%)
    Haemoglobin decreased 0/15 (0%) 1/16 (6.3%)
    Hepatic enzyme increased 0/15 (0%) 1/16 (6.3%)
    Herpes simplex test positive 0/15 (0%) 1/16 (6.3%)
    International normalised ratio increased 0/15 (0%) 2/16 (12.5%)
    Lipase increased 0/15 (0%) 1/16 (6.3%)
    Liver function test abnormal 1/15 (6.7%) 1/16 (6.3%)
    Oxygen saturation decreased 2/15 (13.3%) 1/16 (6.3%)
    Reticulocyte count increased 0/15 (0%) 1/16 (6.3%)
    Sputum culture positive 0/15 (0%) 1/16 (6.3%)
    Staphylococcus test positive 0/15 (0%) 1/16 (6.3%)
    Transaminases increased 0/15 (0%) 2/16 (12.5%)
    Urine output decreased 1/15 (6.7%) 0/16 (0%)
    Weight decreased 1/15 (6.7%) 2/16 (12.5%)
    White blood cell count increased 0/15 (0%) 1/16 (6.3%)
    Metabolism and nutrition disorders
    Acidosis 0/15 (0%) 1/16 (6.3%)
    Dehydration 1/15 (6.7%) 1/16 (6.3%)
    Diabetic ketoacidosis 0/15 (0%) 1/16 (6.3%)
    Fluid overload 0/15 (0%) 3/16 (18.8%)
    Gout 1/15 (6.7%) 0/16 (0%)
    Hyperglycaemia 1/15 (6.7%) 3/16 (18.8%)
    Hyperkalaemia 0/15 (0%) 1/16 (6.3%)
    Hypernatraemia 3/15 (20%) 4/16 (25%)
    Hyperphosphataemia 1/15 (6.7%) 0/16 (0%)
    Hypoalbuminaemia 1/15 (6.7%) 0/16 (0%)
    Hypocalcaemia 2/15 (13.3%) 3/16 (18.8%)
    Hypokalaemia 0/15 (0%) 2/16 (12.5%)
    Hypomagnesaemia 2/15 (13.3%) 1/16 (6.3%)
    Hyponatraemia 1/15 (6.7%) 0/16 (0%)
    Hypophosphataemia 1/15 (6.7%) 1/16 (6.3%)
    Malnutrition 1/15 (6.7%) 4/16 (25%)
    Metabolic alkalosis 1/15 (6.7%) 0/16 (0%)
    Polydipsia 0/15 (0%) 1/16 (6.3%)
    Musculoskeletal and connective tissue disorders
    Back pain 1/15 (6.7%) 0/16 (0%)
    Joint effusion 1/15 (6.7%) 0/16 (0%)
    Muscle atrophy 1/15 (6.7%) 0/16 (0%)
    Muscle necrosis 1/15 (6.7%) 0/16 (0%)
    Muscular weakness 0/15 (0%) 1/16 (6.3%)
    Myalgia 0/15 (0%) 1/16 (6.3%)
    Myopathy 0/15 (0%) 1/16 (6.3%)
    Pain in extremity 0/15 (0%) 1/16 (6.3%)
    Nervous system disorders
    Cerebrospinal fluid leakage 1/15 (6.7%) 0/16 (0%)
    Dizziness 1/15 (6.7%) 0/16 (0%)
    Encephalopathy 2/15 (13.3%) 0/16 (0%)
    Facial paresis 1/15 (6.7%) 0/16 (0%)
    Intensive care unit acquired weakness 0/15 (0%) 1/16 (6.3%)
    Lethargy 0/15 (0%) 1/16 (6.3%)
    Neuropathy peripheral 0/15 (0%) 1/16 (6.3%)
    Presyncope 0/15 (0%) 1/16 (6.3%)
    Somnolence 0/15 (0%) 1/16 (6.3%)
    Product Issues
    Thrombosis in device 1/15 (6.7%) 0/16 (0%)
    Psychiatric disorders
    Agitation 2/15 (13.3%) 3/16 (18.8%)
    Anxiety 2/15 (13.3%) 2/16 (12.5%)
    Delirium 1/15 (6.7%) 2/16 (12.5%)
    Depression 0/15 (0%) 2/16 (12.5%)
    Insomnia 2/15 (13.3%) 0/16 (0%)
    Mental status changes 1/15 (6.7%) 0/16 (0%)
    Nightmare 1/15 (6.7%) 0/16 (0%)
    Renal and urinary disorders
    Acute kidney injury 1/15 (6.7%) 0/16 (0%)
    Haematuria 1/15 (6.7%) 0/16 (0%)
    Oliguria 0/15 (0%) 1/16 (6.3%)
    Polyuria 0/15 (0%) 1/16 (6.3%)
    Renal failure 0/15 (0%) 1/16 (6.3%)
    Reproductive system and breast disorders
    Acquired phimosis 1/15 (6.7%) 0/16 (0%)
    Prostatic obstruction 0/15 (0%) 1/16 (6.3%)
    Scrotal oedema 1/15 (6.7%) 0/16 (0%)
    Respiratory, thoracic and mediastinal disorders
    Apnoeic attack 0/15 (0%) 1/16 (6.3%)
    Aspiration 0/15 (0%) 1/16 (6.3%)
    Atelectasis 0/15 (0%) 4/16 (25%)
    Bronchial obstruction 0/15 (0%) 1/16 (6.3%)
    Bronchopleural fistula 0/15 (0%) 1/16 (6.3%)
    Dyspnoea 1/15 (6.7%) 1/16 (6.3%)
    Epistaxis 0/15 (0%) 1/16 (6.3%)
    Hypoxia 2/15 (13.3%) 3/16 (18.8%)
    Lung disorder 1/15 (6.7%) 0/16 (0%)
    Lung infiltration 0/15 (0%) 1/16 (6.3%)
    Oropharyngeal pain 1/15 (6.7%) 0/16 (0%)
    Pleural effusion 3/15 (20%) 5/16 (31.3%)
    Pneumothorax 2/15 (13.3%) 2/16 (12.5%)
    Productive cough 0/15 (0%) 1/16 (6.3%)
    Pulmonary oedema 1/15 (6.7%) 1/16 (6.3%)
    Respiratory distress 0/15 (0%) 2/16 (12.5%)
    Respiratory failure 1/15 (6.7%) 0/16 (0%)
    Respiratory tract congestion 1/15 (6.7%) 0/16 (0%)
    Stridor 0/15 (0%) 1/16 (6.3%)
    Tachypnoea 1/15 (6.7%) 2/16 (12.5%)
    Wheezing 0/15 (0%) 1/16 (6.3%)
    Skin and subcutaneous tissue disorders
    Decubitus ulcer 1/15 (6.7%) 4/16 (25%)
    Dermatitis 1/15 (6.7%) 0/16 (0%)
    Dermatitis atopic 0/15 (0%) 1/16 (6.3%)
    Rash 0/15 (0%) 1/16 (6.3%)
    Rash maculo-papular 1/15 (6.7%) 0/16 (0%)
    Rash vesicular 1/15 (6.7%) 0/16 (0%)
    Skin discolouration 1/15 (6.7%) 0/16 (0%)
    Skin ulcer 1/15 (6.7%) 0/16 (0%)
    Vascular disorders
    Deep vein thrombosis 0/15 (0%) 2/16 (12.5%)
    Dry gangrene 0/15 (0%) 1/16 (6.3%)
    Extremity necrosis 0/15 (0%) 1/16 (6.3%)
    Flushing 1/15 (6.7%) 0/16 (0%)
    Hypertension 2/15 (13.3%) 1/16 (6.3%)
    Hypotension 6/15 (40%) 4/16 (25%)
    Labile blood pressure 1/15 (6.7%) 0/16 (0%)
    Shock haemorrhagic 1/15 (6.7%) 0/16 (0%)
    Thrombosis 1/15 (6.7%) 0/16 (0%)

    Limitations/Caveats

    [Not Specified]

    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:
    NCT02960854
    Other Study ID Numbers:
    • CA209-923
    First Posted:
    Nov 10, 2016
    Last Update Posted:
    Apr 23, 2019
    Last Verified:
    Apr 1, 2019