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A Phase 1b/2 Study of OMP-59R5 (Tarextumab) in Combination With Etoposide and Platinum Therapy (PINNACLE)

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ClinicalTrials.gov Identifier: NCT01859741
Recruitment Status : Terminated (OMP-59R5 did not improve PFS.)
First Posted : May 22, 2013
Results First Posted : May 1, 2019
Last Update Posted : May 21, 2019
Sponsor:
Information provided by (Responsible Party):
OncoMed Pharmaceuticals, Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Stage IV Small Cell Lung Cancer
Interventions Drug: OMP-59R5
Drug: Etoposide
Drug: Placebo
Drug: Cisplatin or Carboplatin
Enrollment 172
Recruitment Details  
Pre-assignment Details

Phase 1b: Approximately 30 subjects were planned. A total of 27 subjects were enrolled.

Phase 2: Approximately 135 subjects were planned to be randomized. A total of 145 subjects were enrolled/randomized.

Total: 172 subjects were enrolled/randomized (Phase 1b and Phase 2)

Arm/Group Title P1B: OMP-59R5 5mg/kg + ETO + CIS P1B: OMP-59R5 7.5 mg/kg + ETO + CIS P1B: OMP-59R5 10 mg/kg + ETO + CIS P1B: OMP-59R5 12.5 mg/kg + ETO + CIS P1B: OMP-59R5 15 mg/kg + ETO + CIS P1B: OMP-59R5 15mg/kg + ETO + CARB P2: Placebo + CIS or CARB P2: OMP-59R5 15 mg/kg + ETO and CIS or CARB
Hide Arm/Group Description Cohort 1: Subjects receive OMP-59R5 5 mg/kg (administered on Day 1 of each 21-day cycle) along with etoposide 100 mg/m2 (Days 1, 2, and 3) and cisplatin 80 mg/m2 (Day 1). Cohort 2: Subjects receive OMP-59R5 7.5 mg/kg (administered on Day 1 of each 21-day cycle) along with etoposide 100 mg/m2 (Days 1, 2, and 3) and cisplatin 80 mg/m2 (Day 1). Cohort 3: Subjects receive OMP-59R5 10 mg/kg (administered on Day 1 of each 21-day cycle) along with etoposide 100 mg/m2 (Days 1, 2, and 3 and cisplatin 80 mg/m2 on Day 1). Cohort 4: Subjects receive OMP-59R5 12.5 mg/kg (administered on Day 1 of each 21-day cycle) along with etoposide 100 mg/m2 (Days 1, 2, and 3) and cisplatin 80 mg/m2 (Day 1). Cohort 5: Subjects receive OMP-59R5 15 mg/kg (administered on Day 1 of each 21-day cycle) along with etoposide 100 mg/m2 (Days 1, 2, and 3) and cisplatin 80 mg/m2 (Day 1). Cohort 6: Subjects receive OMP-59R5 15 mg/kg (administered on Day 1 of each 21-day cycle) along with etoposide 100 mg/m2 (Days 1, 2, and 3) and carboplatin AUC of 5 mg/mL•min (Day 1). Placebo Arm: Active Arm: Subjects receive placebo and etoposide 100 mg/m2 and cisplatin 75 mg/m2 or carboplatin AUC 5 mg/kg *min Active Arm: Subjects receive OMP-59R5 15 mg/kg and etoposide 100 mg/m2 and cisplatin 75 mg/m2 or carboplatin AUC 5 mg/kg *min
Period Title: Overall Study
Started 3 3 6 3 6 6 72 73
Completed 0 0 0 0 0 0 2 3
Not Completed 3 3 6 3 6 6 70 70
Reason Not Completed
Death             3             2             4             3             5             4             51             51
Lost to Follow-up             0             0             0             0             0             1             0             4
Withdrawal by Subject             0             1             2             0             0             1             1             1
Study Terminated by Sponsor             0             0             0             0             1             0             16             14
Other             0             0             0             0             0             0             2             0
Arm/Group Title P1B: OMP-59R5 5mg/kg + ETO + CIS P1B: OMP-59R5 7.5 mg/kg + ETO + CIS P1B: OMP-59R5 10 mg/kg + ETO + CIS P1B: OMP-59R5 12.5 mg/kg + ETO + CIS P1B: OMP-59R5 15 mg/kg + ETO + CIS P1B: OMP-59R5 15mg/kg + ETO + CARB P2: OMP-59R5 15 mg/kg + ETO and CIS or CARB P2: Placebo + CIS or CARB Total
Hide Arm/Group Description Cohort 1: Subjects receive OMP-59R5 5 mg/kg (administered on Day 1 of each 21-day cycle) along with etoposide 100 mg/m2 (Days 1, 2, and 3) and cisplatin 80 mg/m2 (Day 1). Cohort 2: Subjects receive OMP-59R5 7.5 mg/kg (administered on Day 1 of each 21-day cycle) along with etoposide 100 mg/m2 (Days 1, 2, and 3) and cisplatin 80 mg/m2 (Day 1). Cohort 3: Subjects receive OMP-59R5 10 mg/kg (administered on Day 1 of each 21-day cycle) along with etoposide 100 mg/m2 (Days 1, 2, and 3 and cisplatin 80 mg/m2 on Day 1). Cohort 4: Subjects receive OMP-59R5 12.5 mg/kg (administered on Day 1 of each 21-day cycle) along with etoposide 100 mg/m2 (Days 1, 2, and 3) and cisplatin 80 mg/m2 (Day 1). Cohort 5: Subjects receive OMP-59R5 15 mg/kg (administered on Day 1 of each 21-day cycle) along with etoposide 100 mg/m2 (Days 1, 2, and 3) and cisplatin 80 mg/m2 (Day 1). Cohort 6: Subjects receive OMP-59R5 15 mg/kg (administered on Day 1 of each 21-day cycle) along with etoposide 100 mg/m2 (Days 1, 2, and 3) and carboplatin AUC of 5 mg/mL•min (Day 1). Active Arm: Subjects receive OMP-59R5 15 mg/kg and etoposide 100 mg/m2 and cisplatin 75 mg/m2 or carboplatin AUC 5 mg/kg *min Placebo Arm: Active Arm: Subjects receive placebo and etoposide 100 mg/m2 and cisplatin 75 mg/m2 or carboplatin AUC 5 mg/kg *min Total of all reporting groups
Overall Number of Baseline Participants 3 3 6 3 6 6 73 72 172
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized  
Mean (Full Range)
Unit of measure:  Years
Age Number Analyzed 3 participants 3 participants 6 participants 3 participants 6 participants 6 participants 73 participants 72 participants 172 participants
68.3
(59 to 83)
72.3
(65 to 84)
67.7
(59 to 72)
64.3
(51 to 73)
61.0
(53 to 67)
57.2
(40 to 78)
65.3
(40 to 81)
65.4
(33 to 83)
58.5
(33 to 84)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 3 participants 6 participants 3 participants 6 participants 6 participants 73 participants 72 participants 172 participants
Female
1
  33.3%
1
  33.3%
2
  33.3%
0
   0.0%
3
  50.0%
3
  50.0%
30
  41.1%
37
  51.4%
77
  44.8%
Male
2
  66.7%
2
  66.7%
4
  66.7%
3
 100.0%
3
  50.0%
3
  50.0%
43
  58.9%
35
  48.6%
95
  55.2%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 3 participants 6 participants 3 participants 6 participants 6 participants 73 participants 72 participants 172 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   1.4%
1
   1.4%
2
   1.2%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  16.7%
6
   8.2%
6
   8.3%
13
   7.6%
White
3
 100.0%
3
 100.0%
6
 100.0%
3
 100.0%
6
 100.0%
4
  66.7%
66
  90.4%
64
  88.9%
155
  90.1%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   1.4%
1
   0.6%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  16.7%
0
   0.0%
0
   0.0%
1
   0.6%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 3 participants 3 participants 6 participants 3 participants 6 participants 6 participants 73 participants 72 participants 172 participants
3 3 6 3 6 6 73 72 172
1.Primary Outcome
Title Phase 1b: To Determine the Maximum Tolerated Dose (MTD) of OMP-59R5 When Administered With Etoposide and Cisplatin or Carboplatin (Number of Subjects With DLTs)
Hide Description To determine the MTD of tarextumab when administered on Day 1 of each 21 day cycle along with etoposide 100 mg/m2 on Days 1, 2 and 3, and cisplatin 80 mg/m2 or carboplatin area under the curve (AUC) of 5 mg/mL•min on Day 1 in subjects with untreated extensive stage small cell lung cancer. DLT evaluable population includes all subjects who received at least 1 partial dose of OMP-59R5 during the Phase 1b dose escalation portion of the study including the carboplatin cohort and who had completed Day 21 cycle of 1 OMP-59R5 administration or had discontinued due to drug-related toxicity.
Time Frame Up to 1 year in absence of unacceptable toxicity or disease progression.
Hide Outcome Measure Data
Hide Analysis Population Description
The MTD of OMP-59R5 in combination with etoposide and cisplatin or carboplatin was not reached and the recommended phase 2 dose was determined to be 15 mg/kg every 21-day cycle.
Arm/Group Title P1B: OMP-59R5 5mg/kg + ETO + CIS P1B: OMP-59R5 7.5 mg/kg + ETO + CIS P1B: OMP-59R5 10 mg/kg + ETO + CIS P1B: OMP-59R5 12.5 mg/kg + ETO + CIS P1B: OMP-59R5 15 mg/kg + ETO + CIS P1B: OMP-59R5 15mg/kg + ETO + CARB
Hide Arm/Group Description:
Cohort 1: Subjects receive OMP-59R5 5 mg/kg (administered on Day 1 of each 21-day cycle) along with etoposide 100 mg/m2 (Days 1, 2, and 3) and cisplatin 80 mg/m2 (Day 1).
Cohort 2: Subjects receive OMP-59R5 7.5 mg/kg (administered on Day 1 of each 21-day cycle) along with etoposide 100 mg/m2 (Days 1, 2, and 3) and cisplatin 80 mg/m2 (Day 1).
Cohort 3: Subjects receive OMP-59R5 10 mg/kg (administered on Day 1 of each 21-day cycle) along with etoposide 100 mg/m2 (Days 1, 2, and 3 and cisplatin 80 mg/m2 on Day 1).
Cohort 4: Subjects receive OMP-59R5 12.5 mg/kg (administered on Day 1 of each 21-day cycle) along with etoposide 100 mg/m2 (Days 1, 2, and 3) and cisplatin 80 mg/m2 (Day 1).
Cohort 5: Subjects receive OMP-59R5 15 mg/kg (administered on Day 1 of each 21-day cycle) along with etoposide 100 mg/m2 (Days 1, 2, and 3) and cisplatin 80 mg/m2 (Day 1).
Cohort 6: Subjects receive OMP-59R5 15 mg/kg (administered on Day 1 of each 21-day cycle) along with etoposide 100 mg/m2 (Days 1, 2, and 3) and carboplatin AUC of 5 mg/mL•min (Day 1).
Overall Number of Participants Analyzed 3 3 5 3 6 6
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
1
  20.0%
0
   0.0%
0
   0.0%
0
   0.0%
2.Primary Outcome
Title Phase 1b: Overall Response (Response Evaluable Population)
Hide Description The best overall response is defined as the best Investigator-assessed response recorded from the start of the treatment until disease progression in the following order of importance: Complete Response (CR), Partial Response (PR), Stable Disease (SD), Progressive Disease (PD), Not Evaluable (NE). Response evaluable population includes subjects who received 1 partial dose of OMP-59R5 and at at least 1 post tumor assessment.
Time Frame Up to 1 year in absence of unacceptable toxicity or disease progression.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title P1B: OMP-59R5 5mg/kg + ETO + CIS P1B: OMP-59R5 7.5 mg/kg + ETO + CIS P1B: OMP-59R5 10 mg/kg + ETO + CIS P1B: OMP-59R5 12.5 mg/kg + ETO + CIS P1B: OMP-59R5 15 mg/kg + ETO + CIS P1B: OMP-59R5 15mg/kg + ETO + CARB
Hide Arm/Group Description:
Cohort 1: Subjects receive OMP-59R5 5 mg/kg (administered on Day 1 of each 21-day cycle) along with etoposide 100 mg/m2 (Days 1, 2, and 3) and cisplatin 80 mg/m2 (Day 1).
Cohort 2: Subjects receive OMP-59R5 7.5 mg/kg (administered on Day 1 of each 21-day cycle) along with etoposide 100 mg/m2 (Days 1, 2, and 3) and cisplatin 80 mg/m2 (Day 1).
Cohort 3: Subjects receive OMP-59R5 10 mg/kg (administered on Day 1 of each 21-day cycle) along with etoposide 100 mg/m2 (Days 1, 2, and 3 and cisplatin 80 mg/m2 on Day 1).
Cohort 4: Subjects receive OMP-59R5 12.5 mg/kg (administered on Day 1 of each 21-day cycle) along with etoposide 100 mg/m2 (Days 1, 2, and 3) and cisplatin 80 mg/m2 (Day 1).
Cohort 5: Subjects receive OMP-59R5 15 mg/kg (administered on Day 1 of each 21-day cycle) along with etoposide 100 mg/m2 (Days 1, 2, and 3) and cisplatin 80 mg/m2 (Day 1).
Cohort 6: Subjects receive OMP-59R5 15 mg/kg (administered on Day 1 of each 21-day cycle) along with etoposide 100 mg/m2 (Days 1, 2, and 3) and carboplatin AUC of 5 mg/mL•min (Day 1).
Overall Number of Participants Analyzed 3 3 5 3 6 6
Measure Type: Count of Participants
Unit of Measure: Participants
Complete Response
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Partial Response
3
 100.0%
2
  66.7%
4
  80.0%
2
  66.7%
5
  83.3%
4
  66.7%
Stable Disease
0
   0.0%
1
  33.3%
1
  20.0%
1
  33.3%
0
   0.0%
1
  16.7%
Progressive Disease
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  16.7%
1
  16.7%
Not Evaluated
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Missing
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
3.Primary Outcome
Title Phase 2: Progression Free Survival (ITT Population)
Hide Description To determine the improvement in Progression Free Survival (PFS) resulting from the addition of tarextumab to etoposide and platinum therapy (EP) in subjects receiving first-line therapy for extensive stage small cell lung cancer. PFS is based on the Investigator-assessments of tumor response which is defined as the number of days from randomization until death or disease progression as defined by RECIST criteria for the ITT Population.
Time Frame Up to 1 year until disease progression or death.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title P2: Placebo + CIS or CARB P2: OMP-59R5 15 mg/kg + ETO and CIS or CARB
Hide Arm/Group Description:
Placebo Arm: Active Arm: Subjects receive placebo and etoposide 100 mg/m2 and cisplatin 75 mg/m2 or carboplatin AUC 5 mg/kg *min
Active Arm: Subjects receive OMP-59R5 15 mg/kg and etoposide 100 mg/m2 and cisplatin 75 mg/m2 or carboplatin AUC 5 mg/kg *min
Overall Number of Participants Analyzed 72 73
Measure Type: Count of Participants
Unit of Measure: Participants
Disease Progression or Death
56
  77.8%
51
  69.9%
Did not Progress or Die
16
  22.2%
22
  30.1%
4.Primary Outcome
Title Phase 2: Best Overall Tumor Response Based on Investigator Assessment (ITT Population)
Hide Description The response rate is the number of subjects per treatment arm who have either a complete response (CR) or partial response (PR) for best overall response (according to RECIST criteria) divided by the number of subjects randomized to the respective arms.
Time Frame Up to 1 year in absence of unacceptable toxicity or disease progression
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title P2: Placebo + CIS or CARB P2: OMP-59R5 15 mg/kg + ETO and CIS or CARB
Hide Arm/Group Description:
Placebo Arm: Active Arm: Subjects receive placebo and etoposide 100 mg/m2 and cisplatin 75 mg/m2 or carboplatin AUC 5 mg/kg *min
Active Arm: Subjects receive OMP-59R5 15 mg/kg and etoposide 100 mg/m2 and cisplatin 75 mg/m2 or carboplatin AUC 5 mg/kg *min
Overall Number of Participants Analyzed 72 73
Measure Type: Count of Participants
Unit of Measure: Participants
Complete Response
2
   2.8%
1
   1.4%
Partial Response
49
  68.1%
49
  67.1%
Stable Disease
10
  13.9%
9
  12.3%
Progressive Disease
4
   5.6%
2
   2.7%
Not Evaluable
1
   1.4%
1
   1.4%
No Post-Baseline Tumor Assessment Collected
6
   8.3%
11
  15.1%
Time Frame Adverse event and serious adverse event data are collected from the time of first administration of OMP-59R5, etoposide or platinum therapy up to 4 weeks after the last administration OMP-59R5, etoposide or platinum therapy, whichever is discontinued last but but before the initiation of a new anti-cancer therapy. All cause mortality was collected every 3 months until death, loss to follow-up or study termination by the sponsor (up to 35 months).
Adverse Event Reporting Description

P1: All cause mortality was assessed on the ITT population which was comprised of all subjects who receive at least one partial dose of OMP-59R5. Serious and non-serious AEs were assessed on the ITT population.

P2: All cause mortality was assessed on the ITT population which was comprised of all randomized subjects. Serious and non-serious AEs were assessed on the Safety Population which was defined as all subjects who received one partial dose of OMP-59R5 or placebo.

 
Arm/Group Title P1B: OMP-59R5 5mg/kg + ETO + CIS P1B: OMP-59R5 7.5 mg/kg + ETO + CIS P1B: OMP-59R5 10 mg/kg + ETO + CIS P1B: OMP-59R5 12.5 mg/kg + ETO + CIS P1B: OMP-59R5 15 mg/kg + ETO + CIS P1B: OMP-59R5 15mg/kg + ETO + CARB P2: Placebo + CIS or CARB P2: OMP-59R5 15 mg/kg + ETO and CIS or CARB
Hide Arm/Group Description Cohort 1: Subjects receive OMP-59R5 5 mg/kg (administered on Day 1 of each 21-day cycle) along with etoposide 100 mg/m2 (Days 1, 2, and 3) and cisplatin 80 mg/m2 (Day 1). Cohort 2: Subjects receive OMP-59R5 7.5 mg/kg (administered on Day 1 of each 21-day cycle) along with etoposide 100 mg/m2 (Days 1, 2, and 3) and cisplatin 80 mg/m2 (Day 1). Cohort 3: Subjects receive OMP-59R5 10 mg/kg (administered on Day 1 of each 21-day cycle) along with etoposide 100 mg/m2 (Days 1, 2, and 3 and cisplatin 80 mg/m2 on Day 1). Cohort 4: Subjects receive OMP-59R5 12.5 mg/kg (administered on Day 1 of each 21-day cycle) along with etoposide 100 mg/m2 (Days 1, 2, and 3) and cisplatin 80 mg/m2 (Day 1). Cohort 5: Subjects receive OMP-59R5 15 mg/kg (administered on Day 1 of each 21-day cycle) along with etoposide 100 mg/m2 (Days 1, 2, and 3) and cisplatin 80 mg/m2 (Day 1). Cohort 6: Subjects receive OMP-59R5 15 mg/kg (administered on Day 1 of each 21-day cycle) along with etoposide 100 mg/m2 (Days 1, 2, and 3) and carboplatin AUC of 5 mg/mL•min (Day 1). Placebo Arm: Active Arm: Subjects receive placebo and etoposide 100 mg/m2 and cisplatin 75 mg/m2 or carboplatin AUC 5 mg/kg *min Active Arm: Subjects receive OMP-59R5 15 mg/kg and etoposide 100 mg/m2 and cisplatin 75 mg/m2 or carboplatin AUC 5 mg/kg *min
All-Cause Mortality
P1B: OMP-59R5 5mg/kg + ETO + CIS P1B: OMP-59R5 7.5 mg/kg + ETO + CIS P1B: OMP-59R5 10 mg/kg + ETO + CIS P1B: OMP-59R5 12.5 mg/kg + ETO + CIS P1B: OMP-59R5 15 mg/kg + ETO + CIS P1B: OMP-59R5 15mg/kg + ETO + CARB P2: Placebo + CIS or CARB P2: OMP-59R5 15 mg/kg + ETO and CIS or CARB
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   3/3 (100.00%)      2/3 (66.67%)      4/6 (66.67%)      3/3 (100.00%)      5/6 (83.33%)      4/6 (66.67%)      51/72 (70.83%)      51/73 (69.86%)    
Show Serious Adverse Events Hide Serious Adverse Events
P1B: OMP-59R5 5mg/kg + ETO + CIS P1B: OMP-59R5 7.5 mg/kg + ETO + CIS P1B: OMP-59R5 10 mg/kg + ETO + CIS P1B: OMP-59R5 12.5 mg/kg + ETO + CIS P1B: OMP-59R5 15 mg/kg + ETO + CIS P1B: OMP-59R5 15mg/kg + ETO + CARB P2: Placebo + CIS or CARB P2: OMP-59R5 15 mg/kg + ETO and CIS or CARB
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   1/3 (33.33%)      2/3 (66.67%)      6/6 (100.00%)      1/3 (33.33%)      0/6 (0.00%)      3/6 (50.00%)      29/68 (42.65%)      37/69 (53.62%)    
Blood and lymphatic system disorders                 
Febrile neutropenia  1  0/3 (0.00%)  1/3 (33.33%)  0/6 (0.00%)  1/3 (33.33%)  0/6 (0.00%)  0/6 (0.00%)  1/68 (1.47%)  3/69 (4.35%) 
Thrombocytopenia  1  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  1/3 (33.33%)  0/6 (0.00%)  0/6 (0.00%)  0/68 (0.00%)  1/69 (1.45%) 
Anaemia  1  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/68 (1.47%)  1/69 (1.45%) 
Pancytopenia  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/68 (0.00%)  2/69 (2.90%) 
Neutropenia  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/68 (1.47%)  0/69 (0.00%) 
Cardiac disorders                 
Cardiac arrest  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/68 (0.00%)  2/69 (2.90%) 
Atrial fibrillation  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/3 (33.33%)  0/6 (0.00%)  1/6 (16.67%)  1/68 (1.47%)  1/69 (1.45%) 
Myocardial infarction  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/68 (0.00%)  1/69 (1.45%) 
Acute coronary syndrome  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/68 (1.47%)  0/69 (0.00%) 
Acute myocardial infarction  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  2/68 (2.94%)  0/69 (0.00%) 
Myocardial ischaemia  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/68 (1.47%)  0/69 (0.00%) 
Endocrine disorders                 
Inappropriate antidiuretic hormone secretion  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  3/68 (4.41%)  1/69 (1.45%) 
Gastrointestinal disorders                 
Diarrhoea  1  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/68 (0.00%)  3/69 (4.35%) 
Abdominal pain  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/68 (0.00%)  1/69 (1.45%) 
Gastric haemorrhage  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/68 (0.00%)  1/69 (1.45%) 
Gastrointestinal haemorrhage  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/68 (0.00%)  1/69 (1.45%) 
Intestinal haemorrhage  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/68 (0.00%)  1/69 (1.45%) 
Pancreatitis acute  1  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/68 (1.47%)  0/69 (0.00%) 
Vomiting  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/68 (1.47%)  0/69 (0.00%) 
General disorders                 
Chest pain  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  2/68 (2.94%)  2/69 (2.90%) 
Fatigue  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/68 (1.47%)  1/69 (1.45%) 
Non-cardiac chest pain  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/68 (0.00%)  1/69 (1.45%) 
Asthenia  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/68 (1.47%)  0/69 (0.00%) 
Pyrexia  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  3/68 (4.41%)  0/69 (0.00%) 
Infections and infestations                 
Pneumonia  1  0/3 (0.00%)  0/3 (0.00%)  2/6 (33.33%)  0/3 (0.00%)  0/6 (0.00%)  2/6 (33.33%)  2/68 (2.94%)  12/69 (17.39%) 
Sepsis  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/3 (33.33%)  0/6 (0.00%)  0/6 (0.00%)  0/68 (0.00%)  1/69 (1.45%) 
Clostridium difficile colitis  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/68 (0.00%)  1/69 (1.45%) 
Clostridium difficile infection  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/68 (0.00%)  1/69 (1.45%) 
Diverticulitis  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/68 (0.00%)  1/69 (1.45%) 
Pneumonia legionella  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/68 (0.00%)  1/69 (1.45%) 
Salmonellosis  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/68 (0.00%)  1/69 (1.45%) 
Bronchitis  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/68 (1.47%)  0/69 (0.00%) 
Device related infection  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/68 (1.47%)  0/69 (0.00%) 
Lung abscess  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/68 (1.47%)  0/69 (0.00%) 
Injury, poisoning and procedural complications                 
Spinal compression fracture  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/68 (1.47%)  0/69 (0.00%) 
Fall  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/68 (0.00%)  0/69 (0.00%) 
Investigations                 
Lipase increased  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/68 (0.00%)  1/69 (1.45%) 
Metabolism and nutrition disorders                 
Hyponatraemia  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  5/68 (7.35%)  2/69 (2.90%) 
Dehydration  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  2/68 (2.94%)  0/69 (0.00%) 
Gout  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/68 (1.47%)  0/69 (0.00%) 
Hypercreatininaemia  1  0/3 (0.00%)  1/3 (33.33%)  1/6 (16.67%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/68 (0.00%)  0/69 (0.00%) 
Electrolyte imbalance  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/68 (0.00%)  0/69 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)                 
Small cell lung cancer extensive stage  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/68 (1.47%)  0/69 (0.00%) 
Metastases to central nervous system  1  0/3 (0.00%)  0/3 (0.00%)  2/6 (33.33%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/68 (0.00%)  0/69 (0.00%) 
Small cell lung cancer  1  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/68 (0.00%)  0/69 (0.00%) 
Nervous system disorders                 
Spinal cord compression  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/68 (0.00%)  1/69 (1.45%) 
Convulsion  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0 0/6 (0.00%)  0/6 (0.00%)  1/68 (1.47%)  0/69 (0.00%) 
Hepatic encephalopathy  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/68 (1.47%)  0/69 (0.00%) 
Syncope  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/68 (1.47%)  0/69 (0.00%) 
Partial seizures  1  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/68 (0.00%)  0/69 (0.00%) 
Psychiatric disorders                 
Depression  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/68 (0.00%)  1/69 (1.45%) 
Confusional state  1  1/3 (33.33%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/68 (0.00%)  0/69 (0.00%) 
Renal and urinary disorders                 
Renal failure acute  1  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/68 (0.00%)  0/69 (0.00%) 
Respiratory, thoracic and mediastinal disorders                 
Chronic obstructive pulmonary disease  1  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/68 (0.00%)  2/69 (2.90%) 
Dyspnoea  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/68 (1.47%)  2/69 (2.90%) 
Haemoptysis  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/68 (0.00%)  1/69 (1.45%) 
Pleural effusion  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/68 (1.47%)  1/69 (1.45%) 
Pneumothorax spontaneous  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/68 (0.00%)  1/69 (1.45%) 
Pneumonia aspiration  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/68 (1.47%)  0/69 (0.00%) 
Pulmonary embolism  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  2/68 (2.94%)  0/69 (0.00%) 
Respiratory failure  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/3 (33.33%)  0/6 (0.00%)  0/6 (0.00%)  2/68 (2.94%)  0/69 (0.00%) 
Vascular disorders                 
Hypovolaemic shock  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/68 (0.00%)  1/69 (1.45%) 
Deep vein thrombosis  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/68 (1.47%)  0/69 (0.00%) 
Embolism  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/68 (1.47%)  0/69 (0.00%) 
Hypotension  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  2/68 (2.94%)  0/69 (0.00%) 
Orthostatic hypotension  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/68 (1.47%)  0/69 (0.00%) 
1
Term from vocabulary, MedDRA (16.0)
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
P1B: OMP-59R5 5mg/kg + ETO + CIS P1B: OMP-59R5 7.5 mg/kg + ETO + CIS P1B: OMP-59R5 10 mg/kg + ETO + CIS P1B: OMP-59R5 12.5 mg/kg + ETO + CIS P1B: OMP-59R5 15 mg/kg + ETO + CIS P1B: OMP-59R5 15mg/kg + ETO + CARB P2: Placebo + CIS or CARB P2: OMP-59R5 15 mg/kg + ETO and CIS or CARB
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   3/3 (100.00%)      3/3 (100.00%)      6/6 (100.00%)      3/3 (100.00%)      6/6 (100.00%)      6/6 (100.00%)      68/68 (100.00%)      69/69 (100.00%)    
Blood and lymphatic system disorders                 
Anaemia  1  3/3 (100.00%)  3/3 (100.00%)  2/6 (33.33%)  1/3 (33.33%)  3/6 (50.00%)  4/6 (66.67%)  38/68 (55.88%)  35/69 (50.72%) 
Thrombocytopenia  1  1/3 (33.33%)  2/3 (66.67%)  4/6 (66.67%)  1/3 (33.33%)  4/6 (66.67%)  3/6 (50.00%)  12/68 (17.65%)  40/69 (57.97%) 
Neutropenia  1  2/3 (66.67%)  1/3 (33.33%)  0/6 (0.00%)  1/3 (33.33%)  3/6 (50.00%)  0/6 (0.00%)  32/68 (47.06%)  22/69 (31.88%) 
Febrile neutropenia  1  0/3 (0.00%)  1/3 (33.33%)  0/6 (0.00%)  1/3 (33.33%)  1/6 (16.67%)  0/6 (0.00%)  1/68 (1.47%)  5/69 (7.25%) 
Leukopenia  1  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  1/6 (16.67%)  1/6 (16.67%)  10/68 (14.71%)  6/69 (8.70%) 
Leukocytosis  1  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/68 (0.00%)  0/69 (0.00%) 
Pancytopenia  1  0/3 (0.00%)  1/3 (33.33%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/68 (1.47%)  4/69 (5.80%) 
Lymphopenia  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  2/68 (2.94%)  3/69 (4.35%) 
Iron deficiency anaemia  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/68 (1.47%)  1/69 (1.45%) 
Cardiac disorders                 
Atrial fibrillation  1  1/3 (33.33%)  0/3 (0.00%)  0/6 (0.00%)  1/3 (33.33%)  0/6 (0.00%)  1/6 (16.67%)  1/68 (1.47%)  1/69 (1.45%) 
Tachycardia  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  3/68 (4.41%)  3/69 (4.35%) 
Cardiac arrest  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/68 (0.00%)  2/69 (2.90%) 
Atrial flutter  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/68 (0.00%)  1/69 (1.45%) 
Bradycardia  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/68 (0.00%)  1/69 (1.45%) 
Conduction disorder  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/68 (0.00%)  1/69 (1.45%) 
Myocardial infarction  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/68 (0.00%)  1/69 (1.45%) 
Sinus tachycardia  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/68 (1.47%)  1/69 (1.45%) 
Acute coronary syndrome  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/68 (1.47%)  0/69 (0.00%) 
Acute myocardial infarction  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  2/68 (2.94%)  0/69 (0.00%) 
Angina pectoris  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  2/68 (2.94%)  0/69 (0.00%) 
Myocardial ischaemia  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/68 (1.47%)  0/69 (0.00%) 
Palpitations  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/68 (1.47%)  0/69 (0.00%) 
Supraventricular extrasystoles  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/68 (1.47%)  0/69 (0.00%) 
Ear and labyrinth disorders                 
Tinnitus  1  0/3 (0.00%)  1/3 (33.33%)  1/6 (16.67%)  0/3 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  5/68 (7.35%)  1/69 (1.45%) 
Ear discomfort  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/68 (0.00%)  0/69 (0.00%) 
Ear pain  1  0/3 (0.00%)  1/3 (33.33%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/68 (1.47%)  2/69 (2.90%) 
Hypoacusis  1  0/3 (0.00%)  1/3 (33.33%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/68 (1.47%)  0/69 (0.00%) 
Vertigo  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/68 (0.00%)  3/69 (4.35%) 
Deafness  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/68 (0.00%)  2/69 (2.90%) 
Cerumen impaction  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  2/68 (2.94%)  0/69 (0.00%) 
Deafness bilateral  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/68 (1.47%)  0/69 (0.00%) 
Ear congestion  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/68 (1.47%)  0/69 (0.00%) 
Otorrhoea  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/68 (1.47%)  0/69 (0.00%) 
Vestibular disorder  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/68 (1.47%)  0/69 (0.00%) 
Endocrine disorders                 
Inappropriate antidiuretic hormone secretion  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  3/68 (4.41%)  1/69 (1.45%) 
Adrenal insufficiency  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/68 (0.00%)  1/69 (1.45%) 
Eye disorders                 
Eye pain  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/68 (0.00%)  0/69 (0.00%) 
Vision blurred  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  3/68 (4.41%)  2/69 (2.90%) 
Dry eye  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  2/68 (2.94%)  1/69 (1.45%) 
Visual acuity reduced  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/68 (1.47%)  1/69 (1.45%) 
Blindness unilateral  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/68 (1.47%)  0/69 (0.00%) 
Diplopia  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/68 (1.47%)  0/69 (0.00%) 
Eye pruritus  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  2/68 (2.94%)  0/69 (0.00%) 
Gastrointestinal disorders                 
Diarrhoea  1  1/3 (33.33%)  2/3 (66.67%)  5/6 (83.33%)  3/3 (100.00%)  5/6 (83.33%)  6/6 (100.00%)  23/68 (33.82%)  53/69 (76.81%) 
Nausea  1  3/3 (100.00%)  2/3 (66.67%)  4/6 (66.67%)  2/3 (66.67%)  4/6 (66.67%)  4/6 (66.67%)  44/68 (64.71%)  36/69 (52.17%) 
Vomiting  1  2/3 (66.67%)  1/3 (33.33%)  4/6 (66.67%)  1/3 (33.33%)  3/6 (50.00%)  3/6 (50.00%)  11/68 (16.18%)  22/69 (31.88%) 
Constipation  1  1/3 (33.33%)  1/3 (33.33%)  2/6 (33.33%)  1/3 (33.33%)  2/6 (33.33%)  1/6 (16.67%)  28/68 (41.18%)  11/69 (15.94%) 
Abdominal pain  1  0/3 (0.00%)  0/3 (0.00%)  3/6 (50.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  8/68 (11.76%)  4/69 (5.80%) 
Gastrooesophageal reflux disease  1  1/3 (33.33%)  0/3 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  6/68 (8.82%)  7/69 (10.14%) 
Dyspepsia  1  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  4/68 (5.88%)  4/69 (5.80%) 
Flatulence  1  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  2/68 (2.94%)  3/69 (4.35%) 
Abdominal distension  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  1/68 (1.47%)  4/69 (5.80%) 
Abdominal pain upper  1  0/3 (0.00%)  1/3 (33.33%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  2/68 (2.94%)  0/69 (0.00%) 
Anorectal discomfort  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/68 (0.00%)  0/69 (0.00%) 
Ascites  1  0/3 (0.00%)  1/3 (33.33%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/68 (0.00%)  0/69 (0.00%) 
Dysphagia  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  1/68 (1.47%)  0/69 (0.00%) 
Gingival bleeding  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/68 (0.00%)  1/69 (1.45%) 
Oral pain  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  2/68 (2.94%)  1/69 (1.45%) 
Pancreatitis  1  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/68 (0.00%)  0/69 (0.00%) 
Pancreatitis acute  1  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/68 (1.47%)  0/69 (0.00%) 
Perianal erythema  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/68 (0.00%)  0/69 (0.00%) 
Toothache  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/68 (0.00%)  0/69 (0.00%) 
Umbilical hernia  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/68 (0.00%)  0/69 (0.00%) 
Stomatitis  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  4/68 (5.88%)  11/69 (15.94%) 
Haematochezia  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/68 (0.00%)  3/69 (4.35%) 
Abdominal hernia  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/68 (0.00%)  1/69 (1.45%) 
Abdominal pain lower  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/68 (0.00%)  1/69 (1.45%) 
Dry mouth  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  6/68 (8.82%)  1/69 (1.45%) 
Enterocolitis  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/68 (0.00%)  1/69 (1.45%) 
Epigastric discomfort  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/68 (0.00%)  1/69 (1.45%) 
Faecal incontinence  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/68 (0.00%)  1/69 (1.45%) 
Gastric haemorrhage  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/68 (0.00%)  1/69 (1.45%) 
Gastrointestinal haemorrhage  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/68 (0.00%)  1/69 (1.45%) 
Intestinal haemorrhage  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/68 (0.00%)  1/69 (1.45%) 
Lip dry  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/68 (0.00%)  1/69 (1.45%) 
Lower gastrointestinal haemorrhage  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/68 (0.00%)  1/69 (1.45%) 
Oral discomfort  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/68 (0.00%)  1/69 (1.45%) 
Rectal haemorrhage  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/68 (0.00%)  1/69 (1.45%) 
Abdominal discomfort  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/68 (1.47%)  0/69 (0.00%) 
Abdominal tenderness  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/68 (1.47%)  0/69 (0.00%) 
Colitis  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/68 (1.47%)  0/69 (0.00%) 
Gastritis  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/68 (1.47%)  0/69 (0.00%) 
Haemorrhoids  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  3/68 (4.41%)  0/69 (0.00%) 
Hiatus hernia  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/68 (1.47%)  0/69 (0.00%) 
Lip swelling  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/68 (1.47%)  0/69 (0.00%) 
Loose tooth  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/68 (1.47%)  0/69 (0.00%) 
Oesophageal spasm  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/68 (1.47%)  0/69 (0.00%) 
General disorders                 
Fatigue  1  3/3 (100.00%)  3/3 (100.00%)  3/6 (50.00%)  2/3 (66.67%)  5/6 (83.33%)  1/6 (16.67%)  43/68 (63.24%)  43/69 (62.32%) 
Oedema peripheral  1  3/3 (100.00%)  1/3 (33.33%)  1/6 (16.67%)  1/3 (33.33%)  2/6 (33.33%)  2/6 (33.33%)  13/68 (19.12%)  8/69 (11.59%) 
Pyrexia  1  2/3 (66.67%)  0/3 (0.00%)  0/6 (0.00%)  1/3 (33.33%)  1/6 (16.67%)  1/6 (16.67%)  8/68 (11.76%)  5/69 (7.25%) 
Asthenia  1  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  2/3 (66.67%)  0/6 (0.00%)  1/6 (16.67%)  7/68 (10.29%)  10/69 (14.49%) 
Mucosal inflammation  1  1/3 (33.33%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  1/68 (1.47%)  1/69 (1.45%) 
Catheter site erythema  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/68 (0.00%)  0/69 (0.00%) 
Catheter site pain  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/68 (0.00%)  0/69 (0.00%) 
Chest discomfort  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  1/68 (1.47%)  1/69 (1.45%) 
Chest pain  1  0/3 (0.00%)  1/3 (33.33%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  4/68 (5.88%)  9/69 (13.04%) 
Chills  1  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  4/68 (5.88%)  6/69 (8.70%) 
Device occlusion  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/68 (0.00%)  0/69 (0.00%) 
Generalised oedema  1  1/3 (33.33%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/68 (0.00%)  0/69 (0.00%) 
Oedema  1  1/3 (33.33%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/68 (1.47%)  1/69 (1.45%) 
Malaise  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  2/68 (2.94%)  4/69 (5.80%) 
Infusion site irritation  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/68 (0.00%)  2/69 (2.90%) 
Non-cardiac chest pain  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  2/68 (2.94%)  2/69 (2.90%) 
Pain  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  3/68 (4.41%)  2/69 (2.90%) 
Extravasation  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/68 (0.00%)  1/69 (1.45%) 
Facial pain  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/68 (0.00%)  1/69 (1.45%) 
Infusion site extravasation  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  2/68 (2.94%)  1/69 (1.45%) 
Injection site reaction  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/68 (0.00%)  1/69 (1.45%) 
Face oedema  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/68 (1.47%)  0/69 (0.00%) 
Gait disturbance  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/68 (1.47%)  0/69 (0.00%) 
Peripheral swelling  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/68 (1.47%)  0/69 (0.00%) 
Immune system disorders                 
Drug hypersensitivity  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  2/6 (33.33%)  0/68 (0.00%)  0/69 (0.00%) 
Seasonal allergy  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/68 (0.00%)  2/69 (2.90%) 
Hypersensitivity  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  3/68 (4.41%)  1/69 (1.45%) 
Infections and infestations                 
Pneumonia  1  0/3 (0.00%)  0/3 (0.00%)  2/6 (33.33%)  1/3 (33.33%)  1/6 (16.67%)  2/6 (33.33%)  4/68 (5.88%)  13/69 (18.84%) 
Upper respiratory tract infection  1  0/3 (0.00%)  1/3 (33.33%)  0/6 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  3/68 (4.41%)  4/69 (5.80%) 
Candidiasis  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/3 (33.33%)  0/6 (0.00%)  0/6 (0.00%)  0/68 (0.00%)  0/69 (0.00%) 
Corneal infection  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/68 (0.00%)  0/69 (0.00%) 
Eye infection  1  1/3 (33.33%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/68 (0.00%)  0/69 (0.00%) 
Fungal infection  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/68 (0.00%)  0/69 (0.00%) 
Gastroenteritis  1  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/68 (0.00%)  0/69 (0.00%) 
Influenza  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  1/68 (1.47%)  0/69 (0.00%) 
Oral candidiasis  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  1/68 (1.47%)  3/69 (4.35%) 
Sepsis  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/3 (33.33%)  0/6 (0.00%)  0/6 (0.00%)  1/68 (1.47%)  1/69 (1.45%) 
Urinary tract infection  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  11/68 (16.18%)  8/69 (11.59%) 
Vulval abscess  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/68 (0.00%)  0/69 (0.00%) 
Candida infection  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  2/68 (2.94%)  6/69 (8.70%) 
Clostridium difficile infection  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  2/68 (2.94%)  3/69 (4.35%) 
Diverticulitis  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/68 (1.47%)  2/69 (2.90%) 
Folliculitis  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/68 (1.47%)  2/69 (2.90%) 
Lung infection  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  2/68 (2.94%)  2/69 (2.90%) 
Bronchitis  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  2/68 (2.94%)  1/69 (1.45%) 
Cellulitis  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/68 (1.47%)  1/69 (1.45%) 
Clostridium difficile colitis  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/68 (0.00%)  1/69 (1.45%) 
Furuncle  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/68 (0.00%)  1/69 (1.45%) 
Helicobacter infection  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/68 (0.00%)  1/69 (1.45%) 
Mucosal infection  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/68 (0.00%)  1/69 (1.45%) 
Nasopharyngitis  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/68 (0.00%)  1/69 (1.45%) 
Oral herpes  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/68 (0.00%)  1/69 (1.45%) 
Otitis media  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/68 (1.47%)  1/69 (1.45%) 
Pneumonia legionella  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/68 (0.00%)  1/69 (1.45%) 
Salmonellosis  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/68 (0.00%)  1/69 (1.45%) 
Skin infection  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  2/68 (2.94%)  1/69 (1.45%) 
Tooth infection  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  2/68 (2.94%)  1/69 (1.45%) 
Vaginal infection  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/68 (0.00%)  1/69 (1.45%) 
Viral infection  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/68 (0.00%)  1/69 (1.45%) 
Device related infection  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/68 (1.47%)  0/69 (0.00%) 
Ear infection  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/68 (1.47%)  0/69 (0.00%) 
Hordeolum  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/68 (1.47%)  0/69 (0.00%) 
Influenza  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/68 (1.47%)  0/69 (0.00%) 
Lung abscess  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/68 (1.47%)  0/69 (0.00%) 
Nail infection  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/68 (1.47%)  0/69 (0.00%) 
Oral infection  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/68 (1.47%)  0/69 (0.00%) 
Oropharyngeal candidiasis  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/68 (1.47%)  0/69 (0.00%) 
Sinusitis  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  3/68 (4.41%)  0/69 (0.00%) 
Staphylococcal infection  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/68 (1.47%)  0/69 (0.00%) 
Vaginal cellulitis  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/68 (1.47%)  0/69 (0.00%) 
Injury, poisoning and procedural complications                 
Fall  1  1/3 (33.33%)  0/3 (0.00%)  2/6 (33.33%)  0/3 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  3/68 (4.41%)  3/69 (4.35%) 
Laceration  1  1/3 (33.33%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/68 (0.00%)  0/69 (0.00%) 
Contusion  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  2/68 (2.94%)  3/69 (4.35%) 
Infusion related reaction  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  2/68 (2.94%)  2/69 (2.90%) 
Incision site pain  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/68 (0.00%)  1/69 (1.45%) 
Thermal burn  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/68 (0.00%)  1/69 (1.45%) 
Vascular access complication  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/68 (0.00%)  1/69 (1.45%) 
Arthropod bite  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/68 (1.47%)  0/69 (0.00%) 
Femur fracture  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/68 (1.47%)  0/69 (0.00%) 
Foot fracture  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/68 (1.47%)  0/69 (0.00%) 
Pubis fracture  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/68 (1.47%)  0/69 (0.00%) 
Rib fracture  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/68 (1.47%)  0/69 (0.00%) 
Spinal compression fracture  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/68 (1.47%)  0/69 (0.00%) 
Investigations                 
Weight decreased  1  2/3 (66.67%)  1/3 (33.33%)  3/6 (50.00%)  0/3 (0.00%)  1/6 (16.67%)  1/6 (16.67%)  11/68 (16.18%)  18/69 (26.09%) 
Basophil count increased  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/68 (0.00%)  0/69 (0.00%) 
Blood alkaline phosphatase increased  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/3 (33.33%)  0/6 (0.00%)  0/6 (0.00%)  4/68 (5.88%)  9/69 (13.04%) 
Blood bilirubin decreased  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/68 (0.00%)  0/69 (0.00%) 
Blood cholesterol increased  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/68 (0.00%)  0/69 (0.00%) 
Blood urea increased  1  0/3 (0.00%)  1/3 (33.33%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/68 (0.00%)  0/69 (0.00%) 
Electrocardiogram QT prolonged  1  1/3 (33.33%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/68 (0.00%)  0/69 (0.00%) 
Lymphocyte count decreased  1  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/68 (0.00%)  0/69 (0.00%) 
Weight increased  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  4/68 (5.88%)  1/69 (1.45%) 
Alanine aminotransferase increased  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)