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Trial record 1 of 1 for:    CLO21800205
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A Study of Clofarabine in Combination With Etoposide and Cyclophosphamide in Children With Acute Leukemias.

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ClinicalTrials.gov Identifier: NCT00315705
Recruitment Status : Completed
First Posted : April 19, 2006
Results First Posted : June 30, 2011
Last Update Posted : April 14, 2014
Sponsor:
Information provided by (Responsible Party):
Sanofi ( Genzyme, a Sanofi Company )

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Acute Lymphoblastic Leukemia
Acute Myelogenous Leukemia
Relapsed Leukemia
Interventions Drug: clofarabine
Drug: Etoposide
Drug: Cyclophosphamide
Enrollment 50
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Clofarabine, Etoposide, Cyclophosphamide
Hide Arm/Group Description Phase 1: escalating dosage of the three drugs delivered intravenously. Clofarabine dosage from 20-40 mg/m^2, etoposide dosage from 75-100 mg/m^2, cyclophosphamide dosage from 340-440 mg/m^2. > Phase 2: The recommended phase 2 doses (RP2D) were clofarabine 40 mg/m^2, etoposide 100 mg/m^2 and cyclophosphamide 440 mg/m^2 delivered intravenously
Period Title: Phase 1
Started 25
Completed 0 [1]
Not Completed 25
Reason Not Completed
Refused further treatment             1
Failure to achieve response             8
Disease relapse             4
Scheduled for transplant             9
Death             3
[1]
No Phase 1 participants completed the treatment period (i.e. all 8 cycles and follow-up)
Period Title: Phase 2
Started 25 [1]
Completed 0 [2]
Not Completed 25
Reason Not Completed
Physician Decision             4
Adverse Event             1
Failure to achieve response             3
Disease relapse             1
Scheduled for transplant             8
Other             1
Death             7
[1]
Phase 1 and phase 2 are separate populations
[2]
No Phase 2 participants completed the treatment period (i.e. all 8 cycles and follow-up)
Arm/Group Title Phase 1: Clofarabine, Etoposide, Cyclophosphamide Phase 2: Clofarabine, Etoposide, Cyclophosphamide Total
Hide Arm/Group Description Phase 1: escalating dosage of the three drugs delivered intravenously. Clofarabine dosage from 20-40 mg/m^2, etoposide dosage from 75-100 mg/m^2, cyclophosphamide dosage from 340-440 mg/m^2. Phase 2: The recommended phase 2 doses (RP2D) were clofarabine 40 mg/m^2, etoposide 100 mg/m^2 and cyclophosphamide 440 mg/m^2 delivered intravenously Total of all reporting groups
Overall Number of Baseline Participants 25 25 50
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 25 participants 25 participants 50 participants
9.1  (5.03) 13.2  (5.25) 11.2  (5.49)
[1]
Measure Description: The two study phases were not designed to be reported in the aggregate.
Sex: Female, Male   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 25 participants 25 participants 50 participants
Female
10
  40.0%
9
  36.0%
19
  38.0%
Male
15
  60.0%
16
  64.0%
31
  62.0%
[1]
Measure Description: The two study phases were not designed to be reported in the aggregate.
Ethnicity (NIH/OMB)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 25 participants 25 participants 50 participants
Hispanic or Latino
5
  20.0%
10
  40.0%
15
  30.0%
Not Hispanic or Latino
20
  80.0%
15
  60.0%
35
  70.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
[1]
Measure Description: The two study phases were not designed to be reported in the aggregate.
Race (NIH/OMB)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 25 participants 25 participants 50 participants
American Indian or Alaska Native
0
   0.0%
1
   4.0%
1
   2.0%
Asian
3
  12.0%
2
   8.0%
5
  10.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
4
  16.0%
2
   8.0%
6
  12.0%
White
16
  64.0%
12
  48.0%
28
  56.0%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
2
   8.0%
8
  32.0%
10
  20.0%
[1]
Measure Description: The two study phases were not designed to be reported in the aggregate.
Percent Leukemic Blast Cells   [1] 
Mean (Standard Deviation)
Unit of measure:  Percentage of total blast cells
Number Analyzed 25 participants 25 participants 50 participants
66.8  (24.85) 69.52  (23.566) 68.16  (24.008)
[1]
Measure Description: Percent of leukemic blast cells based on bone marrow aspirate. The two study phases were not designed to be reported in the aggregate.
Absolute Neutrophil Counts   [1] 
Mean (Standard Deviation)
Unit of measure:  10^9/L
Number Analyzed 25 participants 25 participants 50 participants
1.93828  (3.049992) 1.9280  (1.708126) 1.93325  (2.459536)
[1]
Measure Description: The two study phases were not designed to be reported in the aggregate.
White Blood Cell Counts   [1] 
Mean (Standard Deviation)
Unit of measure:  10^9/L
Number Analyzed 25 participants 25 participants 50 participants
8.323  (9.1305) 12.171  (23.0150) 10.247  (17.4370)
[1]
Measure Description: The two study phases were not designed to be reported in the aggregate.
Immunophenotype   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 25 participants 25 participants 50 participants
B cell 13 21 34
T cell 5 1 6
Unknown 2 3 5
not included (AML participants) 5 0 5
[1]
Measure Description: Applies to acute lymphoblastic leukemic (ALL) participants only. Acute myelogenous leukemic (AML) participants are not included. The two study phases were not designed to be reported in the aggregate.
Count of Previous Anti-Leukemic (non-transplant) Treatment Regimens   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 25 participants 25 participants 50 participants
1 regimen 4 4 8
2 regimens 18 14 32
3 regimens 3 7 10
[1]
Measure Description: The two study phases were not designed to be reported in the aggregate.
Participants with Previous Anti-Leukemic Transplant Regimens   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 25 participants 25 participants 50 participants
Transplants 4 4 8
No transplants 21 21 42
[1]
Measure Description: The two study phases were not designed to be reported in the aggregate.
Participants Who Were Refractory to the Most Recent Previous Anti-Leukemic Treatment   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 25 participants 25 participants 50 participants
Yes 7 15 22
No 18 10 28
[1]
Measure Description: The answer "Yes" indicates the number of participants who were refractory (unresponsive) to the most recent anti-leukemic treatment. The answer "No" represents participants who were not refractory. The two study phases were not designed to be reported in the aggregate.
Participant Rating Using the Karnofsky/Lansky Performance Status Scale   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 25 participants 25 participants 50 participants
50 0 2 2
60 0 2 2
70 1 2 3
80 5 3 8
90 7 6 13
100 12 10 22
[1]
Measure Description: Baseline performance was rating using either the Karnofsky Performance Scale for participants greater than 10 years old, or the Lansky Performance Scale for participants 10 years or younger. Both scales range from 0-100 with 0 indicating dead or unresponsive and 100 indicating normal performance. The two study phases were not designed to be reported in the aggregate.
1.Primary Outcome
Title Maximum Tolerated Dose (MTD) in Phase 1
Hide Description

The MTD was to be the highest dose level of clofarabine in combination with etoposide and cyclophosphamide that caused <= 1 of 6 participants to experience a dose limiting toxicity (DLT) with the next higher dose level having at least 2 of 3 or 2 of 6 participants experiencing a DLT. The MTD would be used as the recommended phase 2 dose (RP2D). If the MTD could not be determined, then the target dose of clofarabine 40 mg/m^2, etoposide 100 mg/m^2 and cyclophosphamide 440 mg/m^2 as taken by Cohort 5 was to become the RP2D.

The rating scale used is 0 = not the MTD, 1 = the MTD.

Time Frame Up to Day 42 (Phase 1 portion of study)
Hide Outcome Measure Data
Hide Analysis Population Description
All phase 1 participants
Arm/Group Title Phase 1 - Cohort 1 Phase 1 - Cohort 2 Phase 1 - Cohort 3 Phase 1 - Cohort 4 Phase 1 - Cohort 5
Hide Arm/Group Description:
Participants were treated with clofarabine 20 mg/m^2, etoposide 75 mg/m^2, and cyclophosphamide 340 mg/m^2.
Participants were treated with clofarabine 20 mg/m^2, etoposide 75 mg/m^2, and cyclophosphamide 440 mg/m^2.
Participants were treated with clofarabine 20 mg/m^2, etoposide 100 mg/m^2, and cyclophosphamide 440 mg/m^2.
Participants were treated with clofarabine 30 mg/m^2, etoposide 100 mg/m^2, and cyclophosphamide 440 mg/m^2.
Participants were treated with clofarabine 40 mg/m^2, etoposide 100 mg/m^2, and cyclophosphamide 440 mg/m^2.
Overall Number of Participants Analyzed 3 3 3 10 6
Measure Type: Number
Unit of Measure: units on a scale
0 0 0 0 0
2.Primary Outcome
Title Participants With Dose Limiting Toxicity in Phase 1
Hide Description The number of participants in each cohort that had dose limiting toxicity is summarized. Toxicities were reviewed by an independent Data Safety Monitoring Board (DSMB) who determined if additional participants should be added to the cohort and the criteria for escalating to the next cohort.
Time Frame Up to Day 42 (Phase 1 portion of study)
Hide Outcome Measure Data
Hide Analysis Population Description
All phase 1 participants
Arm/Group Title Phase 1 - Cohort 1 Phase 1 - Cohort 2 Phase 1 - Cohort 3 Phase 1 - Cohort 4 Phase 1 - Cohort 5
Hide Arm/Group Description:
Participants were treated with clofarabine 20 mg/m^2, etoposide 75 mg/m^2, and cyclophosphamide 340 mg/m^2.
Participants were treated with clofarabine 20 mg/m^2, etoposide 75 mg/m^2, and cyclophosphamide 440 mg/m^2.
Participants were treated with clofarabine 20 mg/m^2, etoposide 100 mg/m^2, and cyclophosphamide 440 mg/m^2.
Participants were treated with clofarabine 30 mg/m^2, etoposide 100 mg/m^2, and cyclophosphamide 440 mg/m^2.
Participants were treated with clofarabine 40 mg/m^2, etoposide 100 mg/m^2, and cyclophosphamide 440 mg/m^2.
Overall Number of Participants Analyzed 3 3 3 10 6
Measure Type: Number
Unit of Measure: participants
0 0 0 1 1
3.Primary Outcome
Title Percentage of Participants Achieving A Response Over the First Two Treatment Cycles in Phase 2
Hide Description Response categories 1) complete remission (CR): without circulating blasts or extramedullary disease, bone marrow (BM) with <5% blasts, and platelet (plt)/ANC recovery: ≥75/ ≥0.75 [x 10^9/L] 2) CR in absence of plt recovery (CRp): plt ≥20 to <75 x 10^9/L 3) partial remission (PR): no circulating blasts, appearance of normal hematopoietic progenitors, and either a BM with ≥5% and ≤25% blasts with recovery of plts/ANC or a BM with <5% blasts not meeting CR/CRp definition 4) Overall remission (OR): CR+CRp 5) Any response: CR+CRp+PR.
Time Frame Approximately 28-56 days (Phase 2 portion of study)
Hide Outcome Measure Data
Hide Analysis Population Description
All phase 2 participants
Arm/Group Title Phase 2: Clofarabine, Etoposide, Cyclophosphamide
Hide Arm/Group Description:
Phase 2: The recommended phase 2 doses (RP2D) were clofarabine 40 mg/m^2, etoposide 100 mg/m^2 and cyclophosphamide 440 mg/m^2 delivered intravenously
Overall Number of Participants Analyzed 25
Measure Type: Number
Unit of Measure: percentage of total participants
Complete remission (CR) 28
Complete remission/absence total platelet recovery 16
Partial remission (PR) 12
Overall remission (OR) 44
Any response (CR+CRp+PR) 56
4.Secondary Outcome
Title Summary of Participants With Adverse Events (AEs) in Phase 1
Hide Description Number of participants with AEs that occurred during treatment and follow-up period (45 days after last cycle). Drug-related AEs and SAEs were followed until resolved or mutually agreed by the investigator and Genzyme to discontinue reporting. AEs were classified by the investigator according to severity (graded using National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] version 3.0) and relationship to study drug. The severity scale is: > Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, Grade 4=Life-threatening or disabling, Grade 5=Death related to AE
Time Frame Up to 9.5 months (Phase 1 portion of study)
Hide Outcome Measure Data
Hide Analysis Population Description
All phase 1 participants
Arm/Group Title Phase 1 - Cohort 1 Phase 1 - Cohort 2 Phase 1 - Cohort 3 Phase 1 - Cohort 4 Phase 1 - Cohort 5
Hide Arm/Group Description:
Participants were treated with clofarabine 20 mg/m^2, etoposide 75 mg/m^2, and cyclophosphamide 340 mg/m^2.
Participants were treated with clofarabine 20 mg/m^2, etoposide 75 mg/m^2, and cyclophosphamide 440 mg/m^2.
Participants were treated with clofarabine 20 mg/m^2, etoposide 100 mg/m^2, and cyclophosphamide 440 mg/m^2.
Participants were treated with clofarabine 30 mg/m^2, etoposide 100 mg/m^2, and cyclophosphamide 440 mg/m^2.
Participants were treated with clofarabine 40 mg/m^2, etoposide 100 mg/m^2, and cyclophosphamide 440 mg/m^2.
Overall Number of Participants Analyzed 3 3 3 10 6
Measure Type: Number
Unit of Measure: participants
At least one AE 3 3 3 10 6
At least one AE related to clofarabine 3 3 3 10 6
At least one serious AE 3 3 3 9 6
At least one serious AE related to clofarabine 3 2 3 9 5
Discontinued study due to AE 0 0 0 0 0
Died 3 1 3 9 5
AE with the worst grade of: 1 0 0 0 0 0
AE with the worst grade of: 2 0 0 0 0 0
AE with the worst grade of: 3 2 1 1 3 3
AE with the worst grade of: 4 1 1 2 5 2
AE with the worst grade of: 5 0 1 0 2 1
5.Secondary Outcome
Title Percentage of Participants Achieving A Response Over the First Two Treatment Cycles in Phase 1
Hide Description Response categories 1) complete remission (CR): without circulating blasts or extramedullary disease, bone marrow (BM) with <5% blasts, and platelet (plt)/ANC recovery: ALL ≥75/ ≥0.75 [x 10^9/L]; AML ≥100/ ≥1.0 [x 10^9/L] 2) CR in absence of plt recovery (CRp): ALL plt ≥20 to <75 x 10^9/L; AML plt ≥20 to <100 x 10^9/L 3) partial remission (PR): no circulating blasts, appearance of normal hematopoietic progenitors, and either a BM with ≥5% and ≤25% blasts with recovery of plts/ANC or a BM with <5% blasts not meeting CR/CRp definition 4) Overall remission (OR): CR+CRp 5) Any response: CR+CRp+PR.
Time Frame Approximately 2 months (Phase 1 portion of study)
Hide Outcome Measure Data
Hide Analysis Population Description
All phase 1 participants
Arm/Group Title Phase 1: Clofarabine, Etoposide, Cyclophosphamide
Hide Arm/Group Description:
Phase 1: escalating dosage of the three drugs delivered intravenously. Clofarabine dosage from 20-40 mg/m^2, etoposide dosage from 75-100 mg/m^2, cyclophosphamide dosage from 340-440 mg/m^2.
Overall Number of Participants Analyzed 25
Measure Type: Number
Unit of Measure: percentage of total participants
Complete remission (CR) 40
Complete remission/absence total platelet recovery 24
Partial remission (PR) 0
Overall remission (OR) 64
Any response (CR+CRp+PR) 64
6.Secondary Outcome
Title Time to Remission for Participants Who Had a Response in Phase 1
Hide Description The weeks between start of intervention and remission as assessed by the investigator in Phase 1. Participants who had a complete remission (CR) or complete remission with the absence of total platelet recovery (CRp) are included.
Time Frame up to 8 weeks (Phase 1 portion of study)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in phase 1 who had an overall remission.
Arm/Group Title Phase 1: Clofarabine, Etoposide, Cyclophosphamide
Hide Arm/Group Description:
Phase 1: escalating dosage of the three drugs delivered intravenously. Clofarabine dosage from 20-40 mg/m^2, etoposide dosage from 75-100 mg/m^2, cyclophosphamide dosage from 340-440 mg/m^2.
Overall Number of Participants Analyzed 16
Mean (Standard Deviation)
Unit of Measure: weeks
4.96  (1.912)
7.Secondary Outcome
Title Kaplan Meier Estimate of Duration of Remission (DOR) for Participants Who Achieved Overall Remission (OR) in Phase 1
Hide Description Duration of response is the time from the first objective measurement of complete response (CR) or complete response with the absence of total platelet recovery (CRp) to the date of first objective documentation of disease relapse or death due to any cause, plus one day. For summary purposes, results are presented as weeks.
Time Frame Up to 2 years (Phase 1 portion of study)
Hide Outcome Measure Data
Hide Analysis Population Description
Phase 1 participants who achieved overall remission. Data are censored at date of last known follow-up visit.
Arm/Group Title Phase 1: Clofarabine, Etoposide, Cyclophosphamide
Hide Arm/Group Description:
Phase 1: escalating dosage of the three drugs delivered intravenously. Clofarabine dosage from 20-40 mg/m^2, etoposide dosage from 75-100 mg/m^2, cyclophosphamide dosage from 340-440 mg/m^2.
Overall Number of Participants Analyzed 16
Median (95% Confidence Interval)
Unit of Measure: weeks
18.2
(12.9 to 35.0)
8.Secondary Outcome
Title Kaplan Meier Estimates of Event-free Survival (EFS) for Participants in Phase 1
Hide Description Event-free survival (EFS) is defined as the time from date of first administration of study interventions until the earliest of the following: date of death or date of first response assessment confirming relapse or date of final response assessment which fails to confirm response, plus one day. For summary purposes, results are presented as weeks.
Time Frame Up to 2 years (Phase 1 portion of study)
Hide Outcome Measure Data
Hide Analysis Population Description
All phase 1 participants. Data are censored at date of last known follow-up visit.
Arm/Group Title Phase 1: Clofarabine, Etoposide, Cyclophosphamide
Hide Arm/Group Description:
Phase 1: escalating dosage of the three drugs delivered intravenously. Clofarabine dosage from 20-40 mg/m^2, etoposide dosage from 75-100 mg/m^2, cyclophosphamide dosage from 340-440 mg/m^2.
Overall Number of Participants Analyzed 25
Median (95% Confidence Interval)
Unit of Measure: weeks
19.3
(12.7 to 27.1)
9.Secondary Outcome
Title Number of Participants With 4-month Event Free Survival in Phase 1
Hide Description Number of participants with event-free survival at four months post first dose of therapy. A participant is considered event-free if at month 4 they have not died or had a response assessment confirming a relapse.
Time Frame 4 months (Phase I portion of study)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants
Arm/Group Title Phase 1: Clofarabine, Etoposide, Cyclophosphamide
Hide Arm/Group Description:
Phase 1: escalating dosage of the three drugs delivered intravenously. Clofarabine dosage from 20-40 mg/m^2, etoposide dosage from 75-100 mg/m^2, cyclophosphamide dosage from 340-440 mg/m^2.
Overall Number of Participants Analyzed 25
Measure Type: Number
Unit of Measure: participants
13
10.Secondary Outcome
Title Kaplan Meier Estimates of Overall Survival (OS) for Participants in Phase 1
Hide Description Overall survival is defined as the time from date of first administration of study interventions until date of death, plus one day. For summary purposes, results are presented as weeks.
Time Frame Up to 2 years (Phase 1 portion of study)
Hide Outcome Measure Data
Hide Analysis Population Description
All phase 1 participants
Arm/Group Title Phase 1: Clofarabine, Etoposide, Cyclophosphamide
Hide Arm/Group Description:
Phase 1: escalating dosage of the three drugs delivered intravenously. Clofarabine dosage from 20-40 mg/m^2, etoposide dosage from 75-100 mg/m^2, cyclophosphamide dosage from 340-440 mg/m^2.
Overall Number of Participants Analyzed 25
Median (95% Confidence Interval)
Unit of Measure: weeks
27.1
(18.3 to 42.9)
11.Secondary Outcome
Title Summary of Participants With Adverse Events (AEs) in Phase 2
Hide Description Number of participants with AEs that occurred during treatment and follow-up period (45 days after last cycle). Drug-related AEs and SAEs were followed until resolved or mutually agreed by the investigator and Genzyme to discontinue reporting. AEs were classified by the investigator according to severity (graded using National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] version 3.0) and relationship to study drug. The severity scale is: > Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, Grade 4=Life-threatening or disabling, Grade 5=Death related to AE
Time Frame Up to 9.5 months (Phase 2 portion of study)
Hide Outcome Measure Data
Hide Analysis Population Description
All phase 2 participants
Arm/Group Title Phase 2: Clofarabine, Etoposide, Cyclophosphamide
Hide Arm/Group Description:
Phase 2: The recommended phase 2 doses (RP2D) were clofarabine 40 mg/m^2, etoposide 100 mg/m^2 and cyclophosphamide 440 mg/m^2 delivered intravenously
Overall Number of Participants Analyzed 25
Measure Type: Number
Unit of Measure: participants
At least one AE 25
At least one AE related to clofarabine 25
At least one serious AE 21
At least one serious AE related to clofarabine 20
Discontinued study due to AE 1
Died 16
AE with the worst grade of: 1 0
AE with the worst grade of: 2 0
AE with the worst grade of: 3 1
AE with the worst grade of: 4 16
AE with the worst grade of: 5 8
12.Secondary Outcome
Title Time to Remission for Participants Who Had a Response in Phase 2
Hide Description The weeks between start of intervention and remission as assessed by the investigator in Phase 2. Participants who had a complete remission (CR) or complete remission with the absence of total platelet recovery (CRp) are included.
Time Frame up to 8 weeks (Phase 2 portion of study)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in phase 2 who had an overall remission.
Arm/Group Title Phase 2: Clofarabine, Etoposide, Cyclophosphamide
Hide Arm/Group Description:
Phase 2: The recommended phase 2 doses (RP2D) were clofarabine 40 mg/m^2, etoposide 100 mg/m^2 and cyclophosphamide 440 mg/m^2 delivered intravenously.
Overall Number of Participants Analyzed 11
Mean (Standard Deviation)
Unit of Measure: weeks
4.84  (2.092)
13.Secondary Outcome
Title Kaplan Meier Estimate of Duration of Remission (DOR) for Participants Who Achieved Overall Remission (OR) in Phase 2
Hide Description Duration of response is the time from the first objective measurement of complete response (CR) or complete response with the absence of total platelet recovery (CRp) to the date of first objective documentation of disease relapse or death due to any cause, plus one day. For summary purposes, results are presented as weeks.
Time Frame Up to 2 years (Phase 2 portion of study)
Hide Outcome Measure Data
Hide Analysis Population Description
Phase 2 participants who achieved overall remission. Data are censored at date of last known follow-up visit.
Arm/Group Title Phase 2: Clofarabine, Etoposide, Cyclophosphamide
Hide Arm/Group Description:
Phase 2: The recommended phase 2 doses (RP2D) were clofarabine 40 mg/m^2, etoposide 100 mg/m^2 and cyclophosphamide 440 mg/m^2 delivered intravenously
Overall Number of Participants Analyzed 11
Median (95% Confidence Interval)
Unit of Measure: weeks
67.3 [1] 
(13.4 to NA)
[1]
NA = not estimable because values are mostly censored. Participants with longer DORs have not relapsed, progressed, or died, therefore the upper confidence limit cannot be estimated.
14.Secondary Outcome
Title Kaplan Meier Estimates of Event-free Survival (EFS) for Participants in Phase 2
Hide Description Event-free survival (EFS) is defined as the time from date of first administration of study interventions until the earliest of the following: date of death or date of first response assessment confirming relapse or date of final response assessment which fails to confirm response, plus one day. For summary purposes, results are presented as weeks.
Time Frame Up to 2 years (Phase 2 portion of study)
Hide Outcome Measure Data
Hide Analysis Population Description
All phase 2 participants. Data are censored at date of last known follow-up visit.
Arm/Group Title Phase 2: Clofarabine, Etoposide, Cyclophosphamide
Hide Arm/Group Description:
Phase 2: The recommended phase 2 doses (RP2D) were clofarabine 40 mg/m^2, etoposide 100 mg/m^2 and cyclophosphamide 440 mg/m^2 delivered intravenously
Overall Number of Participants Analyzed 25
Median (95% Confidence Interval)
Unit of Measure: weeks
10.7
(6.7 to 73.9)
15.Secondary Outcome
Title Number of Participants With 4-month Event Free Survival in Phase 2
Hide Description Number of participants with event-free survival at four months post first dose of therapy. A participant is considered event-free if at month 4 they have not died or had a response assessment confirming a relapse.
Time Frame 4 months (Phase 2 portion of study)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants
Arm/Group Title Phase 2: Clofarabine, Etoposide, Cyclophosphamide
Hide Arm/Group Description:
Phase 2: The recommended phase 2 doses (RP2D) were clofarabine 40 mg/m^2, etoposide 100 mg/m^2 and cyclophosphamide 440 mg/m^2 delivered intravenously.
Overall Number of Participants Analyzed 25
Measure Type: Number
Unit of Measure: participants
11
16.Secondary Outcome
Title Kaplan Meier Estimates of Overall Survival (OS) for Participants in Phase 2
Hide Description Overall survival is defined as the time from date of first administration of study interventions until date of death, plus one day. For summary purposes, results are presented as weeks.
Time Frame Up to 2 years (Phase 2 portion of study)
Hide Outcome Measure Data
Hide Analysis Population Description
All phase 2 participants. Data are censored at date of last known follow-up visit.
Arm/Group Title Phase 2: Clofarabine, Etoposide, Cyclophosphamide
Hide Arm/Group Description:
Phase 2: The recommended phase 2 doses (RP2D) were clofarabine 40 mg/m^2, etoposide 100 mg/m^2 and cyclophosphamide 440 mg/m^2 delivered intravenously
Overall Number of Participants Analyzed 25
Median (95% Confidence Interval)
Unit of Measure: weeks
10.7
(8.1 to 38.6)
Time Frame Treatment emergent adverse experiences collected in Phase 1 from day 1 up to 9.5 months. Phase 2 also lasted up to 9.5 months and started after Phase 1.
Adverse Event Reporting Description In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of adverse event tables.
 
Arm/Group Title Phase 1 - Cohort 1 Phase 1 - Cohort 2 Phase 1 - Cohort 3 Phase 1 - Cohort 4 Phase 1 - Cohort 5 Phase 1 - Total Phase 2: Clofarabine, Etoposide, Cyclophosphamide
Hide Arm/Group Description Participants were treated with clofarabine 20 mg/m^2, etoposide 75 mg/m^2, and cyclophosphamide 340 mg/m^2. Participants were treated with clofarabine 20 mg/m^2, etoposide 75 mg/m^2, and cyclophosphamide 440 mg/m^2. Participants were treated with clofarabine 20 mg/m^2, etoposide 100 mg/m^2, and cyclophosphamide 440 mg/m^2. Participants were treated with clofarabine 30 mg/m^2, etoposide 100 mg/m^2, and cyclophosphamide 440 mg/m^2. Participants were treated with clofarabine 40 mg/m^2, etoposide 100 mg/m^2, and cyclophosphamide 440 mg/m^2. All participants from Cohorts 1-5 in Phase 1 Phase 2: The recommended phase 2 doses (RP2D) were clofarabine 40 mg/m^2, etoposide 100 mg/m^2 and cyclophosphamide 440 mg/m^2 delivered intravenously.
All-Cause Mortality
Phase 1 - Cohort 1 Phase 1 - Cohort 2 Phase 1 - Cohort 3 Phase 1 - Cohort 4 Phase 1 - Cohort 5 Phase 1 - Total Phase 2: Clofarabine, Etoposide, Cyclophosphamide
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Phase 1 - Cohort 1 Phase 1 - Cohort 2 Phase 1 - Cohort 3 Phase 1 - Cohort 4 Phase 1 - Cohort 5 Phase 1 - Total Phase 2: Clofarabine, Etoposide, Cyclophosphamide
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%)   3/3 (100.00%)   3/3 (100.00%)   9/10 (90.00%)   6/6 (100.00%)   24/25 (96.00%)   21/25 (84.00%) 
Blood and lymphatic system disorders               
Anaemia  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/10 (10.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Bone marrow failure  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  2/25 (8.00%) 
Disseminated intravascular coagulation  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/10 (10.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Febrile neutropenia  1  3/3 (100.00%)  1/3 (33.33%)  3/3 (100.00%)  7/10 (70.00%)  3/6 (50.00%)  17/25 (68.00%)  15/25 (60.00%) 
Leukocytosis  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Lymphopenia  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Neutropenia  1  1/3 (33.33%)  0/3 (0.00%)  1/3 (33.33%)  1/10 (10.00%)  2/6 (33.33%)  5/25 (20.00%)  0/25 (0.00%) 
Pancytopenia  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Thrombocytopenia  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/10 (10.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Cardiac disorders               
Intracardiac mass  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  1/6 (16.67%)  1/25 (4.00%)  0/25 (0.00%) 
Pericardial effusion  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Ventricular tachycardia  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  1/6 (16.67%)  1/25 (4.00%)  0/25 (0.00%) 
Eye disorders               
Trichiasis  1  0/3 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/10 (0.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Gastrointestinal disorders               
Abdominal pain  1  0/3 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  1/10 (10.00%)  0/6 (0.00%)  2/25 (8.00%)  1/25 (4.00%) 
Ascites  1  0/3 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Caecitis  1  0/3 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  3/10 (30.00%)  0/6 (0.00%)  4/25 (16.00%)  3/25 (12.00%) 
Diarrhoea  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  2/25 (8.00%) 
Enteritis  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/10 (10.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Gastritis  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Gingival bleeding  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Oesophagitis  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/10 (10.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Pancreatitis  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/10 (10.00%)  0/6 (0.00%)  1/25 (4.00%)  2/25 (8.00%) 
Rectal fissure  1  0/3 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/10 (0.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Vomiting  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
General disorders               
Chills  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Generalised oedema  1  0/3 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Mucosal inflammation  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  2/10 (20.00%)  0/6 (0.00%)  2/25 (8.00%)  0/25 (0.00%) 
Multi-organ failure  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  2/25 (8.00%) 
Pyrexia  1  1/3 (33.33%)  0/3 (0.00%)  3/3 (100.00%)  2/10 (20.00%)  0/6 (0.00%)  6/25 (24.00%)  3/25 (12.00%) 
Hepatobiliary disorders               
Hyperbilirubinaemia  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  1/6 (16.67%)  1/25 (4.00%)  2/25 (8.00%) 
Venoocclusive liver disease  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/10 (10.00%)  0/6 (0.00%)  1/25 (4.00%)  3/25 (12.00%) 
Immune system disorders               
Drug hypersensitivity  1  0/3 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Infections and infestations               
Acinetobacter bacteraemia  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Alpha haemolytic streptococcal infection  1  0/3 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  1/10 (10.00%)  0/6 (0.00%)  2/25 (8.00%)  1/25 (4.00%) 
Bacteraemia  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  2/10 (20.00%)  0/6 (0.00%)  2/25 (8.00%)  0/25 (0.00%) 
Bacterial sepsis  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
BK virus infection  1  1/3 (33.33%)  0/3 (0.00%)  0/3 (0.00%)  1/10 (10.00%)  1/6 (16.67%)  3/25 (12.00%)  0/25 (0.00%) 
Bronchopulmonary aspergillosis  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  1/6 (16.67%)  1/25 (4.00%)  2/25 (8.00%) 
Cellulitis  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Central nervous system infection  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/10 (10.00%)  0/6 (0.00%)  1/25 (4.00%)  1/25 (4.00%) 
Cerebral fungal infection  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Clostridial infection  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Clostridium difficile colitis  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Cystitis  1  1/3 (33.33%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Cytomegalovirus viraemia  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/10 (10.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Device related infection  1  1/3 (33.33%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  2/6 (33.33%)  3/25 (12.00%)  2/25 (8.00%) 
Ear infection fungal  1  0/3 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/10 (0.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Enterobacter bacteraemia  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/10 (10.00%)  0/6 (0.00%)  1/25 (4.00%)  1/25 (4.00%) 
Enterobacter infection  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Enterococcal bacteraemia  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  2/25 (8.00%) 
Enterococcal sepsis  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Escherichia bacteraemia  1  0/3 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/10 (0.00%)  0/6 (0.00%)  1/25 (4.00%)  2/25 (8.00%) 
Escherichia infection  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Herpes zoster  1  0/3 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/10 (0.00%)  0/6 (0.00%)  1/25 (4.00%)  1/25 (4.00%) 
Human herpesvirus 6 infection  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/10 (10.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Klebsiella bacteraemia  1  0/3 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/10 (0.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Klebsiella infection  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Lobar pneumonia  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/10 (10.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Lung infection  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  2/10 (20.00%)  0/6 (0.00%)  2/25 (8.00%)  2/25 (8.00%) 
Meningitis bacterial  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  1/6 (16.67%)  1/25 (4.00%)  0/25 (0.00%) 
Meningitis streptococcal  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/10 (10.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Otitis media bacterial  1  1/3 (33.33%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Pelvic abscess  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/10 (10.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Perirectal abscess  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Pneumonia  1  0/3 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/10 (0.00%)  0/6 (0.00%)  1/25 (4.00%)  2/25 (8.00%) 
Pneumonia fungal  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Pulmonary mycosis  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  2/25 (8.00%) 
Sepsis  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  1/6 (16.67%)  1/25 (4.00%)  1/25 (4.00%) 
Septic shock  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  4/25 (16.00%) 
Sinusitis  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/10 (10.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Sinusitis fungal  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Staphylococcal bacteraemia  1  0/3 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  1/10 (10.00%)  0/6 (0.00%)  2/25 (8.00%)  0/25 (0.00%) 
Staphylococcal infection  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/10 (10.00%)  2/6 (33.33%)  3/25 (12.00%)  1/25 (4.00%) 
Staphylococcal sepsis  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Streptococcal bacteraemia  1  0/3 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Streptococcal sepsis  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Upper respiratory tract infection  1  0/3 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Urinary tract infection enterococcal  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  1/6 (16.67%)  1/25 (4.00%)  1/25 (4.00%) 
Viraemia  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Wound infection  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/10 (10.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Wound infection staphylococcal  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Investigations               
Alanine aminotransferase increased  1  0/3 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  1/25 (4.00%)  2/25 (8.00%) 
Aspartate aminotransferase increased  1  0/3 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  1/25 (4.00%)  2/25 (8.00%) 
Blood creatine phosphokinase increased  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Fungal test positive  1  1/3 (33.33%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Lipase increased  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  2/10 (20.00%)  0/6 (0.00%)  2/25 (8.00%)  1/25 (4.00%) 
Polyomavirus test positive  1  0/3 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Metabolism and nutrition disorders               
Decreased appetite  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/10 (10.00%)  0/6 (0.00%)  1/25 (4.00%)  1/25 (4.00%) 
Dehydration  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Hyperglycaemia  1  0/3 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Hypernatraemia  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  1/6 (16.67%)  1/25 (4.00%)  0/25 (0.00%) 
Hyperuricaemia  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Hypokalaemia  1  1/3 (33.33%)  0/3 (0.00%)  1/3 (33.33%)  0/10 (0.00%)  0/6 (0.00%)  2/25 (8.00%)  2/25 (8.00%) 
Hypophosphataemia  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Metabolic acidosis  1  0/3 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Tumour lysis syndrome  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)               
Malignant neoplasm progression  1  0/3 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  1/10 (10.00%)  0/6 (0.00%)  2/25 (8.00%)  0/25 (0.00%) 
Nervous system disorders               
Cerebral haemorrhage  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/10 (10.00%)  0/6 (0.00%)  1/25 (4.00%)  1/25 (4.00%) 
Convulsion  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/10 (10.00%)  1/6 (16.67%)  2/25 (8.00%)  0/25 (0.00%) 
Encephalopathy  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  1/6 (16.67%)  1/25 (4.00%)  0/25 (0.00%) 
Post herpetic neuralgia  1  0/3 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/10 (0.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Renal and urinary disorders               
Cystitis haemorrhagic  1  0/3 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Haematuria  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/10 (10.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Renal failure  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Renal failure acute  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  3/25 (12.00%) 
Renal impairment  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Reproductive system and breast disorders               
Genital rash  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/10 (10.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Respiratory, thoracic and mediastinal disorders               
Acute respiratory distress syndrome  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Hypoxia  1  0/3 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  1/10 (10.00%)  1/6 (16.67%)  3/25 (12.00%)  1/25 (4.00%) 
Pleural effusion  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/10 (10.00%)  1/6 (16.67%)  2/25 (8.00%)  1/25 (4.00%) 
Pneumothorax  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Pulmonary oedema  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  2/25 (8.00%) 
Skin and subcutaneous tissue disorders               
Rash  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Vascular disorders               
Capillary leak syndrome  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  4/25 (16.00%) 
Hypotension  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  4/25 (16.00%) 
Venoocclusive disease  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 13.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Phase 1 - Cohort 1 Phase 1 - Cohort 2 Phase 1 - Cohort 3 Phase 1 - Cohort 4 Phase 1 - Cohort 5 Phase 1 - Total Phase 2: Clofarabine, Etoposide, Cyclophosphamide
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%)   3/3 (100.00%)   3/3 (100.00%)   10/10 (100.00%)   6/6 (100.00%)   25/25 (100.00%)   25/25 (100.00%) 
Blood and lymphatic system disorders               
Anaemia  1  1/3 (33.33%)  1/3 (33.33%)  2/3 (66.67%)  1/10 (10.00%)  2/6 (33.33%)  7/25 (28.00%)  16/25 (64.00%) 
Bone marrow failure  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  1/6 (16.67%)  1/25 (4.00%)  0/25 (0.00%) 
Coagulopathy  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  3/25 (12.00%) 
Disseminated intravascular coagulation  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Febrile neutropenia  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  4/25 (16.00%) 
Leukopenia  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/10 (10.00%)  0/6 (0.00%)  1/25 (4.00%)  4/25 (16.00%) 
Lymphadenopathy  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/10 (10.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Lymphopenia  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/10 (10.00%)  0/6 (0.00%)  1/25 (4.00%)  1/25 (4.00%) 
Neutropenia  1  0/3 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  2/10 (20.00%)  0/6 (0.00%)  3/25 (12.00%)  13/25 (52.00%) 
Pancytopenia  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/10 (10.00%)  1/6 (16.67%)  2/25 (8.00%)  2/25 (8.00%) 
Splenomegaly  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  3/10 (30.00%)  0/6 (0.00%)  3/25 (12.00%)  2/25 (8.00%) 
Thrombocytopenia  1  1/3 (33.33%)  0/3 (0.00%)  2/3 (66.67%)  5/10 (50.00%)  3/6 (50.00%)  11/25 (44.00%)  16/25 (64.00%) 
Cardiac disorders               
Bradycardia  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  1/6 (16.67%)  1/25 (4.00%)  0/25 (0.00%) 
Cardiomyopathy  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Left ventricular dysfunction  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/10 (10.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Left ventricular hypertrophy  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Palpitations  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Pericardial effusion  1  1/3 (33.33%)  1/3 (33.33%)  0/3 (0.00%)  1/10 (10.00%)  0/6 (0.00%)  3/25 (12.00%)  3/25 (12.00%) 
Tachycardia  1  0/3 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  3/10 (30.00%)  2/6 (33.33%)  6/25 (24.00%)  7/25 (28.00%) 
Tricuspid valve incompetence  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Ventricular extrasystoles  1  0/3 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/10 (0.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Ear and labyrinth disorders               
Deafness  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/10 (10.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Deafness neurosensory  1  1/3 (33.33%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Deafness unilateral  1  0/3 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/10 (0.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Ear pain  1  0/3 (0.00%)  0/3 (0.00%)  2/3 (66.67%)  1/10 (10.00%)  1/6 (16.67%)  4/25 (16.00%)  0/25 (0.00%) 
Mixed deafness  1  1/3 (33.33%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Endocrine disorders               
Cushingoid  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/10 (10.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Eye disorders               
Conjunctival hyperaemia  1  0/3 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/10 (0.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Conjunctivitis  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Diplopia  1  0/3 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/10 (0.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Dry eye  1  1/3 (33.33%)  0/3 (0.00%)  1/3 (33.33%)  0/10 (0.00%)  0/6 (0.00%)  2/25 (8.00%)  0/25 (0.00%) 
Ectropion  1  0/3 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/10 (0.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Exophthalmos  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Eye haemorrhage  1  1/3 (33.33%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Eye pain  1  0/3 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/10 (0.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Eye swelling  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Eyelid oedema  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Photophobia  1  0/3 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/10 (0.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Retinal exudates  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  1/6 (16.67%)  1/25 (4.00%)  0/25 (0.00%) 
Retinopathy  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/10 (10.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Scleral haemorrhage  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  1/6 (16.67%)  1/25 (4.00%)  1/25 (4.00%) 
Vision blurred  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Gastrointestinal disorders               
Abdominal distension  1  0/3 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/10 (0.00%)  1/6 (16.67%)  2/25 (8.00%)  1/25 (4.00%) 
Abdominal pain  1  1/3 (33.33%)  0/3 (0.00%)  1/3 (33.33%)  9/10 (90.00%)  2/6 (33.33%)  13/25 (52.00%)  7/25 (28.00%) 
Abdominal pain upper  1  0/3 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  2/10 (20.00%)  0/6 (0.00%)  3/25 (12.00%)  1/25 (4.00%) 
Anal fissure  1  0/3 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/10 (0.00%)  0/6 (0.00%)  1/25 (4.00%)  1/25 (4.00%) 
Ascites  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/10 (10.00%)  0/6 (0.00%)  1/25 (4.00%)  3/25 (12.00%) 
Cheilitis  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  1/6 (16.67%)  1/25 (4.00%)  0/25 (0.00%) 
Colitis  1  0/3 (0.00%)  2/3 (66.67%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  2/25 (8.00%)  1/25 (4.00%) 
Constipation  1  2/3 (66.67%)  1/3 (33.33%)  1/3 (33.33%)  4/10 (40.00%)  1/6 (16.67%)  9/25 (36.00%)  5/25 (20.00%) 
Dental caries  1  0/3 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  2/10 (20.00%)  2/6 (33.33%)  5/25 (20.00%)  1/25 (4.00%) 
Diarrhoea  1  2/3 (66.67%)  2/3 (66.67%)  1/3 (33.33%)  7/10 (70.00%)  5/6 (83.33%)  17/25 (68.00%)  7/25 (28.00%) 
Dry mouth  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Dyspepsia  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/10 (10.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Eructation  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Faecal incontinence  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Gastrointestinal haemorrhage  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/10 (10.00%)  0/6 (0.00%)  1/25 (4.00%)  1/25 (4.00%) 
Gastrooesophageal reflux disease  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/10 (10.00%)  1/6 (16.67%)  2/25 (8.00%)  1/25 (4.00%) 
Gingival bleeding  1  0/3 (0.00%)  0/3 (0.00%)  2/3 (66.67%)  1/10 (10.00%)  0/6 (0.00%)  3/25 (12.00%)  3/25 (12.00%) 
Gingival pain  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/10 (10.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Haematemesis  1  0/3 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  1/10 (10.00%)  0/6 (0.00%)  2/25 (8.00%)  3/25 (12.00%) 
Haematochezia  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Haemorrhoids  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/10 (10.00%)  0/6 (0.00%)  1/25 (4.00%)  1/25 (4.00%) 
Intestinal dilatation  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Lip blister  1  0/3 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Lip dry  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  1/6 (16.67%)  1/25 (4.00%)  0/25 (0.00%) 
Mouth haemorrhage  1  1/3 (33.33%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  1/6 (16.67%)  2/25 (8.00%)  1/25 (4.00%) 
Mouth ulceration  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  2/10 (20.00%)  0/6 (0.00%)  2/25 (8.00%)  0/25 (0.00%) 
Nausea  1  2/3 (66.67%)  2/3 (66.67%)  3/3 (100.00%)  9/10 (90.00%)  5/6 (83.33%)  21/25 (84.00%)  20/25 (80.00%) 
Oesophageal ulcer  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  1/6 (16.67%)  1/25 (4.00%)  0/25 (0.00%) 
Oesophagitis  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Oral disorder  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  1/6 (16.67%)  1/25 (4.00%)  2/25 (8.00%) 
Oral pain  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  3/25 (12.00%) 
Oral pruritus  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/10 (10.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Painful defaecation  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/10 (10.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Pancreatic atrophy  1  0/3 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/10 (0.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Pancreatitis  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  3/25 (12.00%) 
Perianal erythema  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Proctalgia  1  0/3 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  1/10 (10.00%)  1/6 (16.67%)  3/25 (12.00%)  3/25 (12.00%) 
Proctitis  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Rectal fissure  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/10 (10.00%)  0/6 (0.00%)  1/25 (4.00%)  1/25 (4.00%) 
Stomatitis  1  0/3 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  2/10 (20.00%)  0/6 (0.00%)  3/25 (12.00%)  3/25 (12.00%) 
Tongue discolouration  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/10 (10.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Toothache  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Vomiting  1  2/3 (66.67%)  2/3 (66.67%)  3/3 (100.00%)  9/10 (90.00%)  6/6 (100.00%)  22/25 (88.00%)  22/25 (88.00%) 
General disorders               
Application site rash  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/10 (10.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Catheter site erythema  1  0/3 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  0/10 (0.00%)  1/6 (16.67%)  2/25 (8.00%)  1/25 (4.00%) 
Catheter site haematoma  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  1/6 (16.67%)  1/25 (4.00%)  0/25 (0.00%) 
Catheter site pain  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  2/10 (20.00%)  1/6 (16.67%)  3/25 (12.00%)  2/25 (8.00%) 
Catheter site rash  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Catheter site related reaction  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Chest pain  1  0/3 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/10 (0.00%)  0/6 (0.00%)  1/25 (4.00%)  1/25 (4.00%) 
Chills  1  1/3 (33.33%)  0/3 (0.00%)  2/3 (66.67%)  0/10 (0.00%)  1/6 (16.67%)  4/25 (16.00%)  4/25 (16.00%) 
Device occlusion  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Disease progression  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Face oedema  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Fatigue  1  1/3 (33.33%)  0/3 (0.00%)  1/3 (33.33%)  2/10 (20.00%)  2/6 (33.33%)  6/25 (24.00%)  2/25 (8.00%) 
Feeling abnormal  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/10 (10.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Generalised oedema  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  1/6 (16.67%)  1/25 (4.00%)  1/25 (4.00%) 
Hypothermia  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Infusion site extravasation  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  1/6 (16.67%)  1/25 (4.00%)  0/25 (0.00%) 
Injection site haemorrhage  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Irritability  1  0/3 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  1/10 (10.00%)  0/6 (0.00%)  2/25 (8.00%)  0/25 (0.00%) 
Malaise  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/10 (10.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Mucosal inflammation  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  2/10 (20.00%)  3/6 (50.00%)  5/25 (20.00%)  6/25 (24.00%) 
Non-cardiac chest pain  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  1/6 (16.67%)  1/25 (4.00%)  1/25 (4.00%) 
Oedema peripheral  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/10 (10.00%)  1/6 (16.67%)  2/25 (8.00%)  0/25 (0.00%) 
Pain  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/10 (10.00%)  1/6 (16.67%)  2/25 (8.00%)  2/25 (8.00%) 
Pneumatosis  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Puncture site pain  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Pyrexia  1  2/3 (66.67%)  0/3 (0.00%)  1/3 (33.33%)  7/10 (70.00%)  5/6 (83.33%)  15/25 (60.00%)  13/25 (52.00%) 
Hepatobiliary disorders               
Cholecystitis  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  2/25 (8.00%) 
Cholelithiasis  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Cholestasis  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  2/25 (8.00%) 
Gallbladder disorder  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Hepatic steatosis  1  0/3 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/10 (0.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Hepatomegaly  1  0/3 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  3/10 (30.00%)  0/6 (0.00%)  4/25 (16.00%)  5/25 (20.00%) 
Hepatosplenomegaly  1  0/3 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  1/25 (4.00%)  1/25 (4.00%) 
Hyperbilirubinaemia  1  1/3 (33.33%)  0/3 (0.00%)  1/3 (33.33%)  1/10 (10.00%)  0/6 (0.00%)  3/25 (12.00%)  6/25 (24.00%) 
Jaundice  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Immune system disorders               
Drug hypersensitivity  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  2/10 (20.00%)  0/6 (0.00%)  2/25 (8.00%)  0/25 (0.00%) 
Infections and infestations               
Acute sinusitis  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
BK virus infection  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/10 (10.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Brain abscess  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Bronchopulmonary aspergillosis  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Candidiasis  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  3/10 (30.00%)  0/6 (0.00%)  3/25 (12.00%)  0/25 (0.00%) 
Catheter site cellulitis  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Cellulitis  1  1/3 (33.33%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  1/6 (16.67%)  2/25 (8.00%)  2/25 (8.00%) 
Clostridial infection  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Conjunctivitis bacterial  1  0/3 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/10 (0.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Conjunctivitis infective  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/10 (10.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Ear infection  1  0/3 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/10 (0.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Enterobacter bacteraemia  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Enterococcal bacteraemia  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Enterococcal infection  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/10 (10.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Escherichia urinary tract infection  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/10 (10.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Gastrointestinal candidiasis  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/10 (10.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Herpes zoster  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Herpes zoster multi-dermatomal  1  0/3 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/10 (0.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Keratitis herpetic  1  0/3 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/10 (0.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Lung infection  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Onychomycosis  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Oral candidiasis  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Otitis media  1  1/3 (33.33%)  0/3 (0.00%)  0/3 (0.00%)  1/10 (10.00%)  0/6 (0.00%)  2/25 (8.00%)  0/25 (0.00%) 
Otitis media chronic  1  0/3 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/10 (0.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Rhinitis  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/10 (10.00%)  1/6 (16.67%)  2/25 (8.00%)  0/25 (0.00%) 
Sinusitis  1  0/3 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  1/10 (10.00%)  0/6 (0.00%)  2/25 (8.00%)  3/25 (12.00%) 
Sinusitis fungal  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Staphylococcal bacteraemia  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  2/25 (8.00%) 
Staphylococcal infection  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Streptococcal sepsis  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Tooth abscess  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Upper respiratory tract infection  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/10 (10.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Urinary tract infection staphylococcal  1  0/3 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  1/10 (10.00%)  0/6 (0.00%)  2/25 (8.00%)  0/25 (0.00%) 
Viral upper respiratory tract infection  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Wound infection staphylococcal  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Injury, poisoning and procedural complications               
Allergic transfusion reaction  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  1/6 (16.67%)  1/25 (4.00%)  0/25 (0.00%) 
Contusion  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/10 (10.00%)  0/6 (0.00%)  1/25 (4.00%)  2/25 (8.00%) 
Excoriation  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  2/25 (8.00%) 
Head injury  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Incision site haemorrhage  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Joint injury  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/10 (10.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Joint sprain  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/10 (10.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Post lumbar puncture syndrome  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/10 (10.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Post procedural haemorrhage  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  2/25 (8.00%) 
Postoperative wound complication  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  1/6 (16.67%)  1/25 (4.00%)  0/25 (0.00%) 
Procedural pain  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  2/10 (20.00%)  2/6 (33.33%)  4/25 (16.00%)  3/25 (12.00%) 
Skin laceration  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Transfusion reaction  1  0/3 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  1/10 (10.00%)  0/6 (0.00%)  2/25 (8.00%)  2/25 (8.00%) 
Wound  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Investigations               
Alanine aminotransferase increased  1  1/3 (33.33%)  1/3 (33.33%)  0/3 (0.00%)  0/10 (0.00%)  1/6 (16.67%)  3/25 (12.00%)  8/25 (32.00%) 
Antimicrobial susceptibility test sensitive  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Aspartate aminotransferase increased  1  1/3 (33.33%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  1/6 (16.67%)  2/25 (8.00%)  11/25 (44.00%) 
Bacterial test positive  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/10 (10.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Blood albumin decreased  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Blood amylase increased  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  2/25 (8.00%) 
Blood bicarbonate decreased  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Blood creatinine increased  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  2/25 (8.00%) 
Blood glucose increased  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/10 (10.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Blood lactate dehydrogenase increased  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Blood phosphorus increased  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/10 (10.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Blood pressure increased  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/10 (10.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Blood urea increased  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Brain natriuretic peptide increased  1  0/3 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Cardiac murmur  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/10 (10.00%)  1/6 (16.67%)  2/25 (8.00%)  0/25 (0.00%) 
Coagulation test abnormal  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/10 (10.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Culture stool positive  1  0/3 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/10 (0.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Fibrin d dimer increased  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Fungal test positive  1  0/3 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/10 (0.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Haemoglobin decreased  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  1/6 (16.67%)  1/25 (4.00%)  1/25 (4.00%) 
Lipase increased  1  1/3 (33.33%)  1/3 (33.33%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  2/25 (8.00%)  5/25 (20.00%) 
Occult blood positive  1  0/3 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/10 (0.00%)  1/6 (16.67%)  2/25 (8.00%)  1/25 (4.00%) 
Polyomavirus test positive  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/10 (10.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Protein total decreased  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Prothrombin time prolonged  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/10 (10.00%)  0/6 (0.00%)  1/25 (4.00%)  2/25 (8.00%) 
Serum ferritin increased  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Specific gravity urine abnormal  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Specific gravity urine increased  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/10 (10.00%)  1/6 (16.67%)  2/25 (8.00%)  0/25 (0.00%) 
Urine ketone body  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Urine output decreased  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/10 (10.00%)  1/6 (16.67%)  2/25 (8.00%)  0/25 (0.00%) 
Weight decreased  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Metabolism and nutrition disorders               
Decreased appetite  1  1/3 (33.33%)  0/3 (0.00%)  2/3 (66.67%)  5/10 (50.00%)  4/6 (66.67%)  12/25 (48.00%)  15/25 (60.00%) 
Dehydration  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  2/25 (8.00%) 
Fluid imbalance  1  0/3 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  1/10 (10.00%)  1/6 (16.67%)  3/25 (12.00%)  1/25 (4.00%) 
Fluid overload  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/10 (10.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Fluid retention  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Hypercalcaemia  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Hyperglycaemia  1  1/3 (33.33%)  0/3 (0.00%)  1/3 (33.33%)  1/10 (10.00%)  0/6 (0.00%)  3/25 (12.00%)  4/25 (16.00%) 
Hyperkalaemia  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  2/25 (8.00%) 
Hypermagnesaemia  1  1/3 (33.33%)  1/3 (33.33%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  2/25 (8.00%)  0/25 (0.00%) 
Hypernatraemia  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  2/25 (8.00%) 
Hyperphosphataemia  1  1/3 (33.33%)  0/3 (0.00%)  1/3 (33.33%)  0/10 (0.00%)  0/6 (0.00%)  2/25 (8.00%)  4/25 (16.00%) 
Hypertriglyceridaemia  1  0/3 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  1/10 (10.00%)  0/6 (0.00%)  2/25 (8.00%)  1/25 (4.00%) 
Hyperuricaemia  1  1/3 (33.33%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  1/25 (4.00%)  1/25 (4.00%) 
Hypoalbuminaemia  1  1/3 (33.33%)  1/3 (33.33%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  2/25 (8.00%)  3/25 (12.00%) 
Hypocalcaemia  1  1/3 (33.33%)  0/3 (0.00%)  0/3 (0.00%)  1/10 (10.00%)  1/6 (16.67%)  3/25 (12.00%)  6/25 (24.00%) 
Hypoglycaemia  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Hypokalaemia  1  1/3 (33.33%)  2/3 (66.67%)  1/3 (33.33%)  6/10 (60.00%)  1/6 (16.67%)  11/25 (44.00%)  15/25 (60.00%) 
Hypomagnesaemia  1  0/3 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  3/10 (30.00%)  1/6 (16.67%)  5/25 (20.00%)  5/25 (20.00%) 
Hyponatraemia  1  1/3 (33.33%)  1/3 (33.33%)  1/3 (33.33%)  1/10 (10.00%)  2/6 (33.33%)  6/25 (24.00%)  7/25 (28.00%) 
Hypophosphataemia  1  0/3 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  1/10 (10.00%)  1/6 (16.67%)  3/25 (12.00%)  8/25 (32.00%) 
Metabolic acidosis  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  2/25 (8.00%) 
Polydipsia  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Musculoskeletal and connective tissue disorders               
Arthralgia  1  0/3 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  1/10 (10.00%)  0/6 (0.00%)  2/25 (8.00%)  5/25 (20.00%) 
Back pain  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  2/10 (20.00%)  1/6 (16.67%)  3/25 (12.00%)  1/25 (4.00%) 
Bone pain  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  1/6 (16.67%)  1/25 (4.00%)  1/25 (4.00%) 
Flank pain  1  0/3 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/10 (0.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Muscle fatigue  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/10 (10.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Muscle twitching  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Musculoskeletal chest pain  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/10 (10.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Musculoskeletal pain  1  0/3 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  1/10 (10.00%)  0/6 (0.00%)  2/25 (8.00%)  4/25 (16.00%) 
Myalgia  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Neck pain  1  0/3 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  2/10 (20.00%)  1/6 (16.67%)  4/25 (16.00%)  0/25 (0.00%) 
Osteopenia  1  0/3 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  1/10 (10.00%)  0/6 (0.00%)  2/25 (8.00%)  3/25 (12.00%) 
Pain in extremity  1  1/3 (33.33%)  0/3 (0.00%)  2/3 (66.67%)  5/10 (50.00%)  3/6 (50.00%)  11/25 (44.00%)  6/25 (24.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)               
Cancer pain  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Malignant neoplasm progression  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Penile wart  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  1/6 (16.67%)  1/25 (4.00%)  0/25 (0.00%) 
Nervous system disorders               
Amnesia  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Cerebral thrombosis  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Depressed level of consciousness  1  0/3 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/10 (0.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Dizziness  1  0/3 (0.00%)  0/3 (0.00%)  2/3 (66.67%)  4/10 (40.00%)  1/6 (16.67%)  7/25 (28.00%)  2/25 (8.00%) 
Dysaesthesia  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Headache  1  1/3 (33.33%)  0/3 (0.00%)  2/3 (66.67%)  7/10 (70.00%)  4/6 (66.67%)  14/25 (56.00%)  9/25 (36.00%) 
Hydrocephalus  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  1/6 (16.67%)  1/25 (4.00%)  0/25 (0.00%) 
Lethargy  1  0/3 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Paraesthesia  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/10 (10.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Peripheral sensory neuropathy  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/10 (10.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Somnolence  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Syncope  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Tremor  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  2/25 (8.00%) 
Psychiatric disorders               
Agitation  1  0/3 (0.00%)  1/3 (33.33%)  1/3 (33.33%)  0/10 (0.00%)  0/6 (0.00%)  2/25 (8.00%)  2/25 (8.00%) 
Anxiety  1  1/3 (33.33%)  1/3 (33.33%)  2/3 (66.67%)  4/10 (40.00%)  2/6 (33.33%)  10/25 (40.00%)  3/25 (12.00%) 
Depression  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/10 (10.00%)  0/6 (0.00%)  1/25 (4.00%)  1/25 (4.00%) 
Hallucination  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Insomnia  1  1/3 (33.33%)  0/3 (0.00%)  1/3 (33.33%)  1/10 (10.00%)  1/6 (16.67%)  4/25 (16.00%)  3/25 (12.00%) 
Mental status changes  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  2/25 (8.00%) 
Panic attack  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  1/6 (16.67%)  1/25 (4.00%)  0/25 (0.00%) 
Psychotic disorder  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/10 (10.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Social avoidant behaviour  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/10 (10.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Renal and urinary disorders               
Dysuria  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  2/10 (20.00%)  0/6 (0.00%)  2/25 (8.00%)  0/25 (0.00%) 
Haematuria  1  1/3 (33.33%)  1/3 (33.33%)  0/3 (0.00%)  0/10 (0.00%)  2/6 (33.33%)  4/25 (16.00%)  6/25 (24.00%) 
Haemoglobinuria  1  0/3 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Kidney enlargement  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  2/25 (8.00%) 
Micturition urgency  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  1/6 (16.67%)  1/25 (4.00%)  0/25 (0.00%) 
Oliguria  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  2/25 (8.00%) 
Proteinuria  1  0/3 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  1/25 (4.00%)  1/25 (4.00%) 
Renal failure acute  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Urinary bladder haemorrhage  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Reproductive system and breast disorders               
Balanitis  1  0/3 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/10 (0.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Breast pain  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  1/6 (16.67%)  1/25 (4.00%)  0/25 (0.00%) 
Epididymal cyst  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Genital pain  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/10 (10.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Genital rash  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/10 (10.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Metrorrhagia  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Pelvic haematoma  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Pelvic pain  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/10 (10.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Vulvovaginal pruritus  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/10 (10.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Respiratory, thoracic and mediastinal disorders               
Acute respiratory distress syndrome  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Alveolitis  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Atelectasis  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/10 (10.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Cough  1  0/3 (0.00%)  1/3 (33.33%)  1/3 (33.33%)  2/10 (20.00%)  3/6 (50.00%)  7/25 (28.00%)  5/25 (20.00%) 
Dyspnoea  1  1/3 (33.33%)  2/3 (66.67%)  1/3 (33.33%)  0/10 (0.00%)  0/6 (0.00%)  4/25 (16.00%)  4/25 (16.00%) 
Epistaxis  1  0/3 (0.00%)  0/3 (0.00%)  3/3 (100.00%)  3/10 (30.00%)  1/6 (16.67%)  7/25 (28.00%)  4/25 (16.00%) 
Haemoptysis  1  0/3 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/10 (0.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Hiccups  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/10 (10.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Hypoxia  1  0/3 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/10 (0.00%)  1/6 (16.67%)  2/25 (8.00%)  0/25 (0.00%) 
Lung infiltration  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Nasal congestion  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  3/6 (50.00%)  3/25 (12.00%)  2/25 (8.00%) 
Oropharyngeal pain  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  3/10 (30.00%)  2/6 (33.33%)  5/25 (20.00%)  0/25 (0.00%) 
Painful respiration  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  2/10 (20.00%)  1/6 (16.67%)  3/25 (12.00%)  1/25 (4.00%) 
Pleural effusion  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  2/10 (20.00%)  0/6 (0.00%)  2/25 (8.00%)  1/25 (4.00%) 
Pleuritic pain  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/10 (10.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Pneumonitis  1  0/3 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Pneumothorax  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Productive cough  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/10 (10.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Pulmonary oedema  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  1/6 (16.67%)  1/25 (4.00%)  1/25 (4.00%) 
Rhinorrhoea  1  0/3 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  1/10 (10.00%)  1/6 (16.67%)  3/25 (12.00%)  4/25 (16.00%) 
Sinus congestion  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/10 (10.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Sinus disorder  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Sleep apnoea syndrome  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Tachypnoea  1  0/3 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  1/10 (10.00%)  0/6 (0.00%)  2/25 (8.00%)  2/25 (8.00%) 
Upper respiratory tract congestion  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  1/6 (16.67%)  1/25 (4.00%)  0/25 (0.00%) 
Wheezing  1  0/3 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/10 (0.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Skin and subcutaneous tissue disorders               
Acanthosis  1  0/3 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/10 (0.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Alopecia  1  0/3 (0.00%)  0/3 (0.00%)  2/3 (66.67%)  3/10 (30.00%)  1/6 (16.67%)  6/25 (24.00%)  4/25 (16.00%) 
Blister  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Decubitus ulcer  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  2/25 (8.00%) 
Dermatitis  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Drug eruption  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  1/6 (16.67%)  1/25 (4.00%)  0/25 (0.00%) 
Dry skin  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/10 (10.00%)  0/6 (0.00%)  1/25 (4.00%)  1/25 (4.00%) 
Ecchymosis  1  0/3 (0.00%)  0/3 (0.00%)  2/3 (66.67%)  1/10 (10.00%)  1/6 (16.67%)  4/25 (16.00%)  2/25 (8.00%) 
Eczema  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Erythema  1  0/3 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  1/25 (4.00%)  6/25 (24.00%) 
Exfoliative rash  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Hyperhidrosis  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Palmar-plantar erythrodysaesthesia syndrome  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Periorbital oedema  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Petechiae  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  3/10 (30.00%)  0/6 (0.00%)  3/25 (12.00%)  3/25 (12.00%) 
Pruritus  1  0/3 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  5/10 (50.00%)  2/6 (33.33%)  8/25 (32.00%)  6/25 (24.00%) 
Pruritus generalised  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Rash  1  0/3 (0.00%)  2/3 (66.67%)  2/3 (66.67%)  6/10 (60.00%)  4/6 (66.67%)  14/25 (56.00%)  4/25 (16.00%) 
Rash macular  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Rash papular  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/10 (10.00%)  1/6 (16.67%)  2/25 (8.00%)  0/25 (0.00%) 
Red man syndrome  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  1/6 (16.67%)  1/25 (4.00%)  0/25 (0.00%) 
Skin discolouration  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/25 (0.00%)  1/25 (4.00%) 
Skin disorder  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/10 (10.00%)  0/6 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Skin exfoliation  1  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/10 (10.00%)  0/6 (0.00%)