Trial Outcomes & Findings for Study of Erbitux™ (Cetuximab) in Pediatric Patients With Refractory Solid Tumors (NCT NCT00110357)
NCT ID: NCT00110357
Last Updated: 2015-12-24
Results Overview
MTD of cetuximab intravenous (IV) weekly + irinotecan IV x5 days x2 weeks (in a 3-week cycle) and RPIID of cetuximab IV weekly, as measured by dose-limiting toxicities (see outcome measure 2)
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
48 participants
Primary outcome timeframe
Continuous assessment of safety throughout the entire study period and determination of doe-limiting toxicities during and at the end of Cycle 1.
Results posted on
2015-12-24
Participant Flow
48 subjects were enrolled; 1 additional subject withdrew informed consent before any measurements or treatment. 46 subjects (27 in the 1- to 12-yrs-old group and 19 subjects in the 13- to 18-yrs-old group) were treated; 2 subjects in the 13-18 yrs group were not treated, and are NOT included in Participant Flow or Baseline Characteristics tables.
Participant milestones
| Measure |
1- to 12-years-old
|
13- to 18-years-old
|
|---|---|---|
|
Overall Study
STARTED
|
27
|
19
|
|
Overall Study
COMPLETED
|
0
|
0
|
|
Overall Study
NOT COMPLETED
|
27
|
19
|
Reasons for withdrawal
| Measure |
1- to 12-years-old
|
13- to 18-years-old
|
|---|---|---|
|
Overall Study
Deterioration without progression
|
2
|
0
|
|
Overall Study
Disease progression/relapse
|
20
|
15
|
|
Overall Study
Study Closure
|
1
|
0
|
|
Overall Study
Study Drug Toxicity
|
1
|
3
|
|
Overall Study
Withdrawal by Subject
|
3
|
1
|
Baseline Characteristics
Study of Erbitux™ (Cetuximab) in Pediatric Patients With Refractory Solid Tumors
Baseline characteristics by cohort
| Measure |
1- to 12-years-old
n=27 Participants
|
13- to 18-years-old
n=19 Participants
|
Total
n=46 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
8.0 years
n=5 Participants
|
16.0 years
n=7 Participants
|
10 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
15 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
24 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
12 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
22 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
5 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
21 Participants
n=5 Participants
|
14 Participants
n=7 Participants
|
35 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Other
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Disease diagnosis
CNS Primary Tumor
|
17 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
26 Participants
n=5 Participants
|
|
Disease diagnosis
Non-CNS Primary Tumor
|
10 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
20 Participants
n=5 Participants
|
|
Performance Status
>70-100
|
19 Participants
n=5 Participants
|
16 Participants
n=7 Participants
|
35 Participants
n=5 Participants
|
|
Performance Status
≥50-70
|
8 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
|
Performance Status
<50
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Continuous assessment of safety throughout the entire study period and determination of doe-limiting toxicities during and at the end of Cycle 1.Population: As-treated population
MTD of cetuximab intravenous (IV) weekly + irinotecan IV x5 days x2 weeks (in a 3-week cycle) and RPIID of cetuximab IV weekly, as measured by dose-limiting toxicities (see outcome measure 2)
Outcome measures
| Measure |
Group A: 75/20
n=27 Participants
Cetuximab 75 mg/m2 + Irinotecan 20 mg/m2 in participants 1-12 years
|
Group A: 150/20
n=19 Participants
Cetuximab 150 mg/m2 + Irinotecan 20 mg/m2 in participants 1-12 years of age
|
Group A 150/16
Cetuximab 150 mg/m2 + Irinotecan 16 mg/m2 in participants 1-12 years of age
|
Group A: 250/16
Cetuximab 250 mg/m2 + Irinotecan 16 mg/m2 in participants 1-12 years of age
|
Group B: 75/20
Cetuximab 75 mg/m2 + Irinotecan 20 mg/m2 in participants 13-18 years of age
|
Group B: 150/20
Cetuximab 150 mg/m2 + Irinotecan 20 mg/m2 in subjects 13-18 years of age
|
Group B: 250/20
Cetuximab 250 mg/m2 + Irinotecan 20 mg/m2 in participants 13-18 years of age
|
|---|---|---|---|---|---|---|---|
|
Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RPIID) of Cetuximab in Combination With Irinotecan
MTD cetuximab (in combination w/ irinotecan)
|
250 mg/m2
|
250 mg/m2
|
—
|
—
|
—
|
—
|
—
|
|
Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RPIID) of Cetuximab in Combination With Irinotecan
MTD irinotecan (in combination w/ cetuximab)
|
16 mg/m2
|
20 mg/m2
|
—
|
—
|
—
|
—
|
—
|
|
Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RPIID) of Cetuximab in Combination With Irinotecan
RPIID cetuximab (in combination with irinotecan)
|
250 mg/m2
|
250 mg/m2
|
—
|
—
|
—
|
—
|
—
|
|
Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RPIID) of Cetuximab in Combination With Irinotecan
RPIID irinotecan (in combination with cetuximab)
|
16 mg/m2
|
20 mg/m2
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Prior to each 21-day cycle until dose-limiting toxicitiesPopulation: All treated subjects
Dose-limiting toxicities (DLTs)=serious drug side effects preventing further dose escalation. If 1 of the first 3 subjects developed a DLT during cycle 1 up to 3 additional subjects were enrolled at that dose level. The maximum dose level at which DLTs occurred in fewer than 2 out of 3 to 6 subjects was defined as the Maximum Tolerated Dose (MTD).
Outcome measures
| Measure |
Group A: 75/20
n=6 Participants
Cetuximab 75 mg/m2 + Irinotecan 20 mg/m2 in participants 1-12 years
|
Group A: 150/20
n=6 Participants
Cetuximab 150 mg/m2 + Irinotecan 20 mg/m2 in participants 1-12 years of age
|
Group A 150/16
n=3 Participants
Cetuximab 150 mg/m2 + Irinotecan 16 mg/m2 in participants 1-12 years of age
|
Group A: 250/16
n=12 Participants
Cetuximab 250 mg/m2 + Irinotecan 16 mg/m2 in participants 1-12 years of age
|
Group B: 75/20
n=8 Participants
Cetuximab 75 mg/m2 + Irinotecan 20 mg/m2 in participants 13-18 years of age
|
Group B: 150/20
n=4 Participants
Cetuximab 150 mg/m2 + Irinotecan 20 mg/m2 in subjects 13-18 years of age
|
Group B: 250/20
n=7 Participants
Cetuximab 250 mg/m2 + Irinotecan 20 mg/m2 in participants 13-18 years of age
|
|---|---|---|---|---|---|---|---|
|
Number of Participants With a Dose-Limiting Toxicity
Subjects with a dose-limiting toxicity
|
1 Participants
|
2 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With a Dose-Limiting Toxicity
Subjects with no dose-limiting toxicity
|
5 Participants
|
4 Participants
|
3 Participants
|
12 Participants
|
7 Participants
|
4 Participants
|
6 Participants
|
SECONDARY outcome
Timeframe: up to 168 hours after the start of the cetuximab infusion during the first 21-day cycle of the studyThe single dose pharmacokinetics (PK) of cetuximab was administered with an intravenous dose of irinotecan 16 to 20 mg/m2; Cmax was evaluated based on concentration-time profile.
Outcome measures
| Measure |
Group A: 75/20
n=7 Participants
Cetuximab 75 mg/m2 + Irinotecan 20 mg/m2 in participants 1-12 years
|
Group A: 150/20
n=7 Participants
Cetuximab 150 mg/m2 + Irinotecan 20 mg/m2 in participants 1-12 years of age
|
Group A 150/16
n=9 Participants
Cetuximab 150 mg/m2 + Irinotecan 16 mg/m2 in participants 1-12 years of age
|
Group A: 250/16
n=4 Participants
Cetuximab 250 mg/m2 + Irinotecan 16 mg/m2 in participants 1-12 years of age
|
Group B: 75/20
n=2 Participants
Cetuximab 75 mg/m2 + Irinotecan 20 mg/m2 in participants 13-18 years of age
|
Group B: 150/20
n=6 Participants
Cetuximab 150 mg/m2 + Irinotecan 20 mg/m2 in subjects 13-18 years of age
|
Group B: 250/20
Cetuximab 250 mg/m2 + Irinotecan 20 mg/m2 in participants 13-18 years of age
|
|---|---|---|---|---|---|---|---|
|
Maximum Plasma Concentration (Cmax)
|
50.5 µg/mL
Standard Deviation 16.7
|
112.9 µg/mL
Standard Deviation 24.7
|
163.7 µg/mL
Standard Deviation 31.1
|
53.4 µg/mL
Standard Deviation 21.7
|
83.1 µg/mL
Standard Deviation 13.2
|
148.5 µg/mL
Standard Deviation 28.1
|
—
|
SECONDARY outcome
Timeframe: up to 168 hours after the start of the cetuximab infusion during the first 21-day cycle of the studyThe single dose PK of cetuximab was administered with an intravenous dose of irinotecan 16 to 20 mg/m2; AUC(INF) was evaluated based on concentration-time profile.
Outcome measures
| Measure |
Group A: 75/20
n=7 Participants
Cetuximab 75 mg/m2 + Irinotecan 20 mg/m2 in participants 1-12 years
|
Group A: 150/20
n=7 Participants
Cetuximab 150 mg/m2 + Irinotecan 20 mg/m2 in participants 1-12 years of age
|
Group A 150/16
n=9 Participants
Cetuximab 150 mg/m2 + Irinotecan 16 mg/m2 in participants 1-12 years of age
|
Group A: 250/16
n=4 Participants
Cetuximab 250 mg/m2 + Irinotecan 16 mg/m2 in participants 1-12 years of age
|
Group B: 75/20
n=2 Participants
Cetuximab 75 mg/m2 + Irinotecan 20 mg/m2 in participants 13-18 years of age
|
Group B: 150/20
n=6 Participants
Cetuximab 150 mg/m2 + Irinotecan 20 mg/m2 in subjects 13-18 years of age
|
Group B: 250/20
Cetuximab 250 mg/m2 + Irinotecan 20 mg/m2 in participants 13-18 years of age
|
|---|---|---|---|---|---|---|---|
|
Area Under the Curve, Extrapolated to Infinity (AUC[INF])
|
1598.3 µg•h/mL
Standard Deviation 863.32
|
8871.2 µg•h/mL
Standard Deviation 1861.1
|
17706.0 µg•h/mL
Standard Deviation 6384.5
|
1925.2 µg•h/mL
Standard Deviation 460.6
|
7027.3 µg•h/mL
Standard Deviation 239.5
|
13410.4 µg•h/mL
Standard Deviation 5484.5
|
—
|
SECONDARY outcome
Timeframe: up to 168 hours after the start of the cetuximab infusion during the first 21-day cycle of the studyThe single dose PK of cetuximab was administered with an intravenous dose of irinotecan 16 to 20 mg/m2; T-half was evaluated based on concentration-time profile.
Outcome measures
| Measure |
Group A: 75/20
n=7 Participants
Cetuximab 75 mg/m2 + Irinotecan 20 mg/m2 in participants 1-12 years
|
Group A: 150/20
n=7 Participants
Cetuximab 150 mg/m2 + Irinotecan 20 mg/m2 in participants 1-12 years of age
|
Group A 150/16
n=9 Participants
Cetuximab 150 mg/m2 + Irinotecan 16 mg/m2 in participants 1-12 years of age
|
Group A: 250/16
n=4 Participants
Cetuximab 250 mg/m2 + Irinotecan 16 mg/m2 in participants 1-12 years of age
|
Group B: 75/20
n=2 Participants
Cetuximab 75 mg/m2 + Irinotecan 20 mg/m2 in participants 13-18 years of age
|
Group B: 150/20
n=6 Participants
Cetuximab 150 mg/m2 + Irinotecan 20 mg/m2 in subjects 13-18 years of age
|
Group B: 250/20
Cetuximab 250 mg/m2 + Irinotecan 20 mg/m2 in participants 13-18 years of age
|
|---|---|---|---|---|---|---|---|
|
Terminal Half-Life (T-Half)
|
31.0 hours
Standard Deviation 13.9
|
75.2 hours
Standard Deviation 18.7
|
110.3 hours
Standard Deviation 43.1
|
37.9 hours
Standard Deviation 6.3
|
61.1 hours
Standard Deviation 10.5
|
81.9 hours
Standard Deviation 20.4
|
—
|
SECONDARY outcome
Timeframe: up to 168 hours after the start of the cetuximab infusion during the first 21-day cycle of the studyThe single dose PK of cetuximab was administered with an intravenous dose of irinotecan 16 to 20 mg/m2; CL/BSA was evaluated based on concentration-time profile.
Outcome measures
| Measure |
Group A: 75/20
n=7 Participants
Cetuximab 75 mg/m2 + Irinotecan 20 mg/m2 in participants 1-12 years
|
Group A: 150/20
n=7 Participants
Cetuximab 150 mg/m2 + Irinotecan 20 mg/m2 in participants 1-12 years of age
|
Group A 150/16
n=9 Participants
Cetuximab 150 mg/m2 + Irinotecan 16 mg/m2 in participants 1-12 years of age
|
Group A: 250/16
n=4 Participants
Cetuximab 250 mg/m2 + Irinotecan 16 mg/m2 in participants 1-12 years of age
|
Group B: 75/20
n=2 Participants
Cetuximab 75 mg/m2 + Irinotecan 20 mg/m2 in participants 13-18 years of age
|
Group B: 150/20
n=6 Participants
Cetuximab 150 mg/m2 + Irinotecan 20 mg/m2 in subjects 13-18 years of age
|
Group B: 250/20
Cetuximab 250 mg/m2 + Irinotecan 20 mg/m2 in participants 13-18 years of age
|
|---|---|---|---|---|---|---|---|
|
Clearance Corrected for Body Surface Area (CL/BSA)
|
0.057 L/h/m2
Standard Deviation 0.041
|
0.017 L/h/m2
Standard Deviation 0.004
|
0.015 L/h/m2
Standard Deviation 0.005
|
0.040 L/h/m2
Standard Deviation 0.010
|
0.021 L/h/m2
Standard Deviation 0.001
|
0.020 L/h/m2
Standard Deviation 0.009
|
—
|
SECONDARY outcome
Timeframe: up to 168 hours after the start of the cetuximab infusion during the first 21-day cycle of the studyThe single dose PK of cetuximab was administered with an intravenous dose of irinotecan 16 to 20 mg/m2; VSS/BSA was evaluated based on concentration-time profile.
Outcome measures
| Measure |
Group A: 75/20
n=7 Participants
Cetuximab 75 mg/m2 + Irinotecan 20 mg/m2 in participants 1-12 years
|
Group A: 150/20
n=7 Participants
Cetuximab 150 mg/m2 + Irinotecan 20 mg/m2 in participants 1-12 years of age
|
Group A 150/16
n=9 Participants
Cetuximab 150 mg/m2 + Irinotecan 16 mg/m2 in participants 1-12 years of age
|
Group A: 250/16
n=4 Participants
Cetuximab 250 mg/m2 + Irinotecan 16 mg/m2 in participants 1-12 years of age
|
Group B: 75/20
n=2 Participants
Cetuximab 75 mg/m2 + Irinotecan 20 mg/m2 in participants 13-18 years of age
|
Group B: 150/20
n=6 Participants
Cetuximab 150 mg/m2 + Irinotecan 20 mg/m2 in subjects 13-18 years of age
|
Group B: 250/20
Cetuximab 250 mg/m2 + Irinotecan 20 mg/m2 in participants 13-18 years of age
|
|---|---|---|---|---|---|---|---|
|
Volume of Distribution at Steady State Corrected for Body Surface Area (VSS/BSA)
|
2.081 L/m2
Standard Deviation 0.666
|
1.860 L/m2
Standard Deviation 0.564
|
2.157 L/m2
Standard Deviation 0.362
|
2.138 L/m2
Standard Deviation 0.453
|
1.887 L/m2
Standard Deviation 0.262
|
2.179 L/m2
Standard Deviation 0.250
|
—
|
SECONDARY outcome
Timeframe: Every other 21-day cyclePopulation: All treated subjects
Non-central nervous system (CNS) tumors evaluated using Response Evaluation Criteria In Solid Tumors (RECIST), criteria to define when cancer patients improve ("respond"), stay the same ("stable"), or worsen ("progression"). CNS tumors evaluated based on measurements by investigator, dependence on corticosteroids, and neurologic exam.
Outcome measures
| Measure |
Group A: 75/20
n=26 Participants
Cetuximab 75 mg/m2 + Irinotecan 20 mg/m2 in participants 1-12 years
|
Group A: 150/20
n=20 Participants
Cetuximab 150 mg/m2 + Irinotecan 20 mg/m2 in participants 1-12 years of age
|
Group A 150/16
Cetuximab 150 mg/m2 + Irinotecan 16 mg/m2 in participants 1-12 years of age
|
Group A: 250/16
Cetuximab 250 mg/m2 + Irinotecan 16 mg/m2 in participants 1-12 years of age
|
Group B: 75/20
Cetuximab 75 mg/m2 + Irinotecan 20 mg/m2 in participants 13-18 years of age
|
Group B: 150/20
Cetuximab 150 mg/m2 + Irinotecan 20 mg/m2 in subjects 13-18 years of age
|
Group B: 250/20
Cetuximab 250 mg/m2 + Irinotecan 20 mg/m2 in participants 13-18 years of age
|
|---|---|---|---|---|---|---|---|
|
Tumor Response
Partial Response
|
2 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
|
Tumor Response
Stable Disease
|
10 Participants
|
8 Participants
|
—
|
—
|
—
|
—
|
—
|
|
Tumor Response
Progressive Disease
|
10 Participants
|
11 Participants
|
—
|
—
|
—
|
—
|
—
|
|
Tumor Response
Not Assessable/Unable to Determine
|
4 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Blood was drawn immediately prior to cetuximab infusions, on a 21-day cyclePopulation: Cohort comprises all enrolled participants who were tested for HACA. Evaluable participants had normal baseline HACA (≤ 7 ng/dL) and ≥1 postbaseline HACA levels; unevaluable participants either did not have enough sample for analysis or did not have a pre- and postinfusion sample for immunogenicity.
In order to be considered positive for anti-cetuximab a sample had to: 1) be evaluable (i.e., have a pre and at least one post-treatment timepoint), 2) have an anti-cetuximab value \> 7 ng/mL and 3) have a post-treatment sample at least twice the pre-treatment level.
Outcome measures
| Measure |
Group A: 75/20
n=42 Participants
Cetuximab 75 mg/m2 + Irinotecan 20 mg/m2 in participants 1-12 years
|
Group A: 150/20
Cetuximab 150 mg/m2 + Irinotecan 20 mg/m2 in participants 1-12 years of age
|
Group A 150/16
Cetuximab 150 mg/m2 + Irinotecan 16 mg/m2 in participants 1-12 years of age
|
Group A: 250/16
Cetuximab 250 mg/m2 + Irinotecan 16 mg/m2 in participants 1-12 years of age
|
Group B: 75/20
Cetuximab 75 mg/m2 + Irinotecan 20 mg/m2 in participants 13-18 years of age
|
Group B: 150/20
Cetuximab 150 mg/m2 + Irinotecan 20 mg/m2 in subjects 13-18 years of age
|
Group B: 250/20
Cetuximab 250 mg/m2 + Irinotecan 20 mg/m2 in participants 13-18 years of age
|
|---|---|---|---|---|---|---|---|
|
Human Anti-cetuximab Antibody (HACA) Response
Evaluable Participants
|
27 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Human Anti-cetuximab Antibody (HACA) Response
Unevaluable Participants
|
15 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Human Anti-cetuximab Antibody (HACA) Response
Participants with positive HACA level
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Weekly throughout the study and every 4 weeks thereafterPopulation: All treated patients
Toxicity assessments performed at least weekly from the 1st dose of study drug until at least 30 days after the final dose of study drug and thereafter every 4 weeks until all study-related toxicities resolved, returned to baseline, or were deemed irreversible, whichever was longer. Grade 3=severe AE; grade 4=disabling or life threatening.
Outcome measures
| Measure |
Group A: 75/20
n=6 Participants
Cetuximab 75 mg/m2 + Irinotecan 20 mg/m2 in participants 1-12 years
|
Group A: 150/20
n=6 Participants
Cetuximab 150 mg/m2 + Irinotecan 20 mg/m2 in participants 1-12 years of age
|
Group A 150/16
n=3 Participants
Cetuximab 150 mg/m2 + Irinotecan 16 mg/m2 in participants 1-12 years of age
|
Group A: 250/16
n=12 Participants
Cetuximab 250 mg/m2 + Irinotecan 16 mg/m2 in participants 1-12 years of age
|
Group B: 75/20
n=8 Participants
Cetuximab 75 mg/m2 + Irinotecan 20 mg/m2 in participants 13-18 years of age
|
Group B: 150/20
n=4 Participants
Cetuximab 150 mg/m2 + Irinotecan 20 mg/m2 in subjects 13-18 years of age
|
Group B: 250/20
n=7 Participants
Cetuximab 250 mg/m2 + Irinotecan 20 mg/m2 in participants 13-18 years of age
|
|---|---|---|---|---|---|---|---|
|
Number of Deaths, Serious Adverse Events (SAEs), and Adverse Events (AEs)
Deaths (total)
|
0 Participants
|
5 Participants
|
2 Participants
|
5 Participants
|
3 Participants
|
1 Participants
|
1 Participants
|
|
Number of Deaths, Serious Adverse Events (SAEs), and Adverse Events (AEs)
Deaths within 30 days of last dose
|
0 Participants
|
2 Participants
|
0 Participants
|
3 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Deaths, Serious Adverse Events (SAEs), and Adverse Events (AEs)
AEs leading to discontinuation of study treatment
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
2 Participants
|
1 Participants
|
0 Participants
|
|
Number of Deaths, Serious Adverse Events (SAEs), and Adverse Events (AEs)
Grade 3-4 AEs
|
4 Participants
|
4 Participants
|
2 Participants
|
5 Participants
|
7 Participants
|
4 Participants
|
4 Participants
|
|
Number of Deaths, Serious Adverse Events (SAEs), and Adverse Events (AEs)
SAEs
|
2 Participants
|
4 Participants
|
0 Participants
|
6 Participants
|
5 Participants
|
3 Participants
|
4 Participants
|
SECONDARY outcome
Timeframe: pretreatment visit, prior to each treatment cycle, weekly, and at the end of treatmentBlood samples were collected at selected times (pretreatment visit, prior to each treatment cycle, weekly, and at the end of treatment) for clinical laboratory evaluations. Grade 3= Severe AE; Grade 4=Life-threatening or disabling AE
Outcome measures
| Measure |
Group A: 75/20
n=6 Participants
Cetuximab 75 mg/m2 + Irinotecan 20 mg/m2 in participants 1-12 years
|
Group A: 150/20
n=3 Participants
Cetuximab 150 mg/m2 + Irinotecan 20 mg/m2 in participants 1-12 years of age
|
Group A 150/16
n=6 Participants
Cetuximab 150 mg/m2 + Irinotecan 16 mg/m2 in participants 1-12 years of age
|
Group A: 250/16
n=12 Participants
Cetuximab 250 mg/m2 + Irinotecan 16 mg/m2 in participants 1-12 years of age
|
Group B: 75/20
n=7 Participants
Cetuximab 75 mg/m2 + Irinotecan 20 mg/m2 in participants 13-18 years of age
|
Group B: 150/20
n=4 Participants
Cetuximab 150 mg/m2 + Irinotecan 20 mg/m2 in subjects 13-18 years of age
|
Group B: 250/20
n=7 Participants
Cetuximab 250 mg/m2 + Irinotecan 20 mg/m2 in participants 13-18 years of age
|
|---|---|---|---|---|---|---|---|
|
Grade 3-4 Laboratory Abnormalities - Leukopenia
|
3 Participants
|
0 Participants
|
3 Participants
|
4 Participants
|
2 Participants
|
2 Participants
|
4 Participants
|
SECONDARY outcome
Timeframe: pretreatment visit, prior to each treatment cycle, weekly, and at the end of treatmentBlood samples were collected at selected times (pretreatment visit, prior to each treatment cycle, weekly, and at the end of treatment) for clinical laboratory evaluations. Grade 3= Severe and undesirable AE; Grade 4=Life-threatening or disabling AE
Outcome measures
| Measure |
Group A: 75/20
n=6 Participants
Cetuximab 75 mg/m2 + Irinotecan 20 mg/m2 in participants 1-12 years
|
Group A: 150/20
n=3 Participants
Cetuximab 150 mg/m2 + Irinotecan 20 mg/m2 in participants 1-12 years of age
|
Group A 150/16
n=4 Participants
Cetuximab 150 mg/m2 + Irinotecan 16 mg/m2 in participants 1-12 years of age
|
Group A: 250/16
n=10 Participants
Cetuximab 250 mg/m2 + Irinotecan 16 mg/m2 in participants 1-12 years of age
|
Group B: 75/20
n=6 Participants
Cetuximab 75 mg/m2 + Irinotecan 20 mg/m2 in participants 13-18 years of age
|
Group B: 150/20
n=3 Participants
Cetuximab 150 mg/m2 + Irinotecan 20 mg/m2 in subjects 13-18 years of age
|
Group B: 250/20
n=6 Participants
Cetuximab 250 mg/m2 + Irinotecan 20 mg/m2 in participants 13-18 years of age
|
|---|---|---|---|---|---|---|---|
|
Grade 3-4 Laboratory Abnormalities - Neutropenia
|
3 Participants
|
0 Participants
|
3 Participants
|
3 Participants
|
3 Participants
|
1 Participants
|
4 Participants
|
SECONDARY outcome
Timeframe: pretreatment visit, prior to each treatment cycle, weekly, and at the end of treatmentBlood samples collected at selected times (pretreatment visit, prior to each treatment cycle, weekly, and at the end of treatment) for clinical laboratory evaluations. Grade 3= Severe AE; Grade 4=Life-threatening or disabling AE
Outcome measures
| Measure |
Group A: 75/20
n=6 Participants
Cetuximab 75 mg/m2 + Irinotecan 20 mg/m2 in participants 1-12 years
|
Group A: 150/20
n=3 Participants
Cetuximab 150 mg/m2 + Irinotecan 20 mg/m2 in participants 1-12 years of age
|
Group A 150/16
n=6 Participants
Cetuximab 150 mg/m2 + Irinotecan 16 mg/m2 in participants 1-12 years of age
|
Group A: 250/16
n=12 Participants
Cetuximab 250 mg/m2 + Irinotecan 16 mg/m2 in participants 1-12 years of age
|
Group B: 75/20
n=7 Participants
Cetuximab 75 mg/m2 + Irinotecan 20 mg/m2 in participants 13-18 years of age
|
Group B: 150/20
n=4 Participants
Cetuximab 150 mg/m2 + Irinotecan 20 mg/m2 in subjects 13-18 years of age
|
Group B: 250/20
n=7 Participants
Cetuximab 250 mg/m2 + Irinotecan 20 mg/m2 in participants 13-18 years of age
|
|---|---|---|---|---|---|---|---|
|
Grade 3-4 Laboratory Abnormalities - Thrombocytopenia
|
1 Participants
|
0 Participants
|
3 Participants
|
2 Participants
|
0 Participants
|
0 Participants
|
4 Participants
|
SECONDARY outcome
Timeframe: pretreatment visit, prior to each treatment cycle, weekly, and at the end of treatmentBlood samples were collected at selected times (pretreatment visit, prior to each treatment cycle, weekly, and at the end of treatment) for clinical laboratory evaluations. Grade 3= Severe AE; Grade 4=Life-threatening or disabling AE
Outcome measures
| Measure |
Group A: 75/20
Cetuximab 75 mg/m2 + Irinotecan 20 mg/m2 in participants 1-12 years
|
Group A: 150/20
Cetuximab 150 mg/m2 + Irinotecan 20 mg/m2 in participants 1-12 years of age
|
Group A 150/16
Cetuximab 150 mg/m2 + Irinotecan 16 mg/m2 in participants 1-12 years of age
|
Group A: 250/16
n=12 Participants
Cetuximab 250 mg/m2 + Irinotecan 16 mg/m2 in participants 1-12 years of age
|
Group B: 75/20
Cetuximab 75 mg/m2 + Irinotecan 20 mg/m2 in participants 13-18 years of age
|
Group B: 150/20
Cetuximab 150 mg/m2 + Irinotecan 20 mg/m2 in subjects 13-18 years of age
|
Group B: 250/20
Cetuximab 250 mg/m2 + Irinotecan 20 mg/m2 in participants 13-18 years of age
|
|---|---|---|---|---|---|---|---|
|
Grade 3/4 Laboratory Abnormalities - Hypomagnesemia
|
—
|
—
|
—
|
1 Participants
|
—
|
—
|
—
|
Adverse Events
01 75 mg/m2 CET + 20 mg/m2 IRI
Serious events: 7 serious events
Other events: 14 other events
Deaths: 0 deaths
02 150 mg/m2 CET + 20 mg/m2 IRI
Serious events: 7 serious events
Other events: 8 other events
Deaths: 0 deaths
03 150 mg/m2 CET + 16 mg/m2 IRI
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
04 250 mg/m2 CET + 16 mg/m2 IRI
Serious events: 6 serious events
Other events: 12 other events
Deaths: 0 deaths
05 250 mg/m2 CET + 20 mg/m2 IRI
Serious events: 4 serious events
Other events: 7 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
01 75 mg/m2 CET + 20 mg/m2 IRI
n=14 participants at risk
|
02 150 mg/m2 CET + 20 mg/m2 IRI
n=10 participants at risk
|
03 150 mg/m2 CET + 16 mg/m2 IRI
n=3 participants at risk
|
04 250 mg/m2 CET + 16 mg/m2 IRI
n=12 participants at risk
|
05 250 mg/m2 CET + 20 mg/m2 IRI
n=7 participants at risk
|
|---|---|---|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
DYSPNOEA
|
7.1%
1/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Infections and infestations
GASTROINTESTINAL INFECTION
|
7.1%
1/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Metabolism and nutrition disorders
HYPOMAGNESAEMIA
|
0.00%
0/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
14.3%
1/7
|
|
Investigations
NEUTROPHIL COUNT
|
0.00%
0/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
14.3%
1/7
|
|
Nervous system disorders
SOMNOLENCE
|
0.00%
0/14
|
10.0%
1/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Reproductive system and breast disorders
VAGINAL HAEMORRHAGE
|
0.00%
0/14
|
10.0%
1/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Nervous system disorders
CRANIAL NEUROPATHY
|
0.00%
0/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
14.3%
1/7
|
|
General disorders
DISEASE PROGRESSION
|
0.00%
0/14
|
10.0%
1/10
|
0.00%
0/3
|
8.3%
1/12
|
0.00%
0/7
|
|
Gastrointestinal disorders
DYSPHAGIA
|
0.00%
0/14
|
10.0%
1/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Investigations
HAEMOGLOBIN
|
0.00%
0/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
14.3%
1/7
|
|
Nervous system disorders
HEADACHE
|
7.1%
1/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Metabolism and nutrition disorders
HYPOKALAEMIA
|
7.1%
1/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
14.3%
1/7
|
|
Respiratory, thoracic and mediastinal disorders
HYPOXIA
|
0.00%
0/14
|
0.00%
0/10
|
0.00%
0/3
|
8.3%
1/12
|
0.00%
0/7
|
|
Infections and infestations
INFECTION
|
14.3%
2/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
14.3%
1/7
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MALIGNANT NEOPLASM PROGRESSION
|
0.00%
0/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
42.9%
3/7
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
NEOPLASM MALIGNANT
|
0.00%
0/14
|
0.00%
0/10
|
0.00%
0/3
|
8.3%
1/12
|
0.00%
0/7
|
|
Renal and urinary disorders
URINARY RETENTION
|
0.00%
0/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
14.3%
1/7
|
|
Investigations
WHITE BLOOD CELL COUNT
|
0.00%
0/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
14.3%
1/7
|
|
Infections and infestations
CATHETER RELATED INFECTION
|
7.1%
1/14
|
10.0%
1/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Infections and infestations
CENTRAL LINE INFECTION
|
0.00%
0/14
|
0.00%
0/10
|
0.00%
0/3
|
8.3%
1/12
|
0.00%
0/7
|
|
Surgical and medical procedures
ELECTIVE SURGERY
|
0.00%
0/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
14.3%
1/7
|
|
Gastrointestinal disorders
ILEUS
|
7.1%
1/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
General disorders
INFUSION RELATED REACTION
|
0.00%
0/14
|
0.00%
0/10
|
0.00%
0/3
|
8.3%
1/12
|
0.00%
0/7
|
|
Infections and infestations
NEUTROPENIC INFECTION
|
14.3%
2/14
|
10.0%
1/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
General disorders
PYREXIA
|
14.3%
2/14
|
30.0%
3/10
|
0.00%
0/3
|
8.3%
1/12
|
0.00%
0/7
|
|
Skin and subcutaneous tissue disorders
SKIN LESION
|
7.1%
1/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Gastrointestinal disorders
ABDOMINAL DISTENSION
|
7.1%
1/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Gastrointestinal disorders
CONSTIPATION
|
0.00%
0/14
|
10.0%
1/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Metabolism and nutrition disorders
DEHYDRATION
|
14.3%
2/14
|
10.0%
1/10
|
0.00%
0/3
|
16.7%
2/12
|
0.00%
0/7
|
|
Investigations
GRANULOCYTE COUNT DECREASED
|
7.1%
1/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Metabolism and nutrition disorders
HYPONATRAEMIA
|
7.1%
1/14
|
0.00%
0/10
|
0.00%
0/3
|
8.3%
1/12
|
0.00%
0/7
|
|
Gastrointestinal disorders
NAUSEA
|
7.1%
1/14
|
30.0%
3/10
|
0.00%
0/3
|
0.00%
0/12
|
14.3%
1/7
|
|
General disorders
PAIN
|
7.1%
1/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Investigations
PLATELET COUNT
|
0.00%
0/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
14.3%
1/7
|
|
Respiratory, thoracic and mediastinal disorders
RESPIRATORY DISTRESS
|
0.00%
0/14
|
10.0%
1/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Gastrointestinal disorders
VOMITING
|
21.4%
3/14
|
20.0%
2/10
|
0.00%
0/3
|
8.3%
1/12
|
14.3%
1/7
|
|
Gastrointestinal disorders
ASCITES
|
0.00%
0/14
|
0.00%
0/10
|
0.00%
0/3
|
8.3%
1/12
|
0.00%
0/7
|
|
Gastrointestinal disorders
COLITIS
|
7.1%
1/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Hepatobiliary disorders
HEPATIC FUNCTION ABNORMAL
|
0.00%
0/14
|
0.00%
0/10
|
0.00%
0/3
|
8.3%
1/12
|
0.00%
0/7
|
|
Immune system disorders
HYPERSENSITIVITY
|
14.3%
2/14
|
10.0%
1/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Vascular disorders
HYPOTENSION
|
0.00%
0/14
|
10.0%
1/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Blood and lymphatic system disorders
LYMPHOPENIA
|
0.00%
0/14
|
10.0%
1/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MALIGNANT PLEURAL EFFUSION
|
0.00%
0/14
|
0.00%
0/10
|
0.00%
0/3
|
8.3%
1/12
|
0.00%
0/7
|
|
Respiratory, thoracic and mediastinal disorders
PLEURAL EFFUSION
|
7.1%
1/14
|
0.00%
0/10
|
0.00%
0/3
|
8.3%
1/12
|
0.00%
0/7
|
|
Infections and infestations
ROTAVIRUS INFECTION
|
7.1%
1/14
|
0.00%
0/10
|
0.00%
0/3
|
8.3%
1/12
|
0.00%
0/7
|
|
Gastrointestinal disorders
ABDOMINAL PAIN
|
0.00%
0/14
|
10.0%
1/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Gastrointestinal disorders
FAECAL INCONTINENCE
|
0.00%
0/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
14.3%
1/7
|
|
General disorders
FATIGUE
|
14.3%
2/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Hepatobiliary disorders
HYPERBILIRUBINAEMIA
|
0.00%
0/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
14.3%
1/7
|
|
Metabolism and nutrition disorders
HYPOCALCAEMIA
|
0.00%
0/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
14.3%
1/7
|
|
Respiratory, thoracic and mediastinal disorders
RESPIRATORY FAILURE
|
0.00%
0/14
|
10.0%
1/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Investigations
BLOOD BICARBONATE DECREASED
|
0.00%
0/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
14.3%
1/7
|
|
Investigations
BLOOD POTASSIUM DECREASED
|
0.00%
0/14
|
0.00%
0/10
|
0.00%
0/3
|
8.3%
1/12
|
0.00%
0/7
|
|
Gastrointestinal disorders
DIARRHOEA
|
14.3%
2/14
|
20.0%
2/10
|
0.00%
0/3
|
8.3%
1/12
|
14.3%
1/7
|
|
Hepatobiliary disorders
GALLBLADDER OBSTRUCTION
|
0.00%
0/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
14.3%
1/7
|
|
Nervous system disorders
HYDROCEPHALUS
|
7.1%
1/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Infections and infestations
PNEUMONIA
|
7.1%
1/14
|
10.0%
1/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Investigations
WEIGHT DECREASED
|
7.1%
1/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
General disorders
CHILLS
|
0.00%
0/14
|
20.0%
2/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Blood and lymphatic system disorders
FEBRILE NEUTROPENIA
|
7.1%
1/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
14.3%
1/7
|
|
Nervous system disorders
LETHARGY
|
0.00%
0/14
|
10.0%
1/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
General disorders
NECROSIS
|
7.1%
1/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Nervous system disorders
PERIPHERAL MOTOR NEUROPATHY
|
0.00%
0/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
14.3%
1/7
|
|
Nervous system disorders
PERIPHERAL SENSORY NEUROPATHY
|
0.00%
0/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
14.3%
1/7
|
|
Infections and infestations
SEPSIS
|
0.00%
0/14
|
10.0%
1/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Nervous system disorders
SPEECH DISORDER
|
0.00%
0/14
|
10.0%
1/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
Other adverse events
| Measure |
01 75 mg/m2 CET + 20 mg/m2 IRI
n=14 participants at risk
|
02 150 mg/m2 CET + 20 mg/m2 IRI
n=10 participants at risk
|
03 150 mg/m2 CET + 16 mg/m2 IRI
n=3 participants at risk
|
04 250 mg/m2 CET + 16 mg/m2 IRI
n=12 participants at risk
|
05 250 mg/m2 CET + 20 mg/m2 IRI
n=7 participants at risk
|
|---|---|---|---|---|---|
|
Investigations
WHITE BLOOD CELL COUNT INCREASED
|
14.3%
2/14
|
0.00%
0/10
|
33.3%
1/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Gastrointestinal disorders
ABDOMINAL DISTENSION
|
0.00%
0/14
|
10.0%
1/10
|
0.00%
0/3
|
16.7%
2/12
|
0.00%
0/7
|
|
Skin and subcutaneous tissue disorders
ACNE
|
0.00%
0/14
|
10.0%
1/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Renal and urinary disorders
ANURIA
|
0.00%
0/14
|
10.0%
1/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Infections and infestations
LOCALISED INFECTION
|
7.1%
1/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Investigations
ASPARTATE AMINOTRANSFERASE INCREASED
|
7.1%
1/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
14.3%
1/7
|
|
Investigations
BLOOD SODIUM DECREASED
|
14.3%
2/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Infections and infestations
CATHETER SITE INFECTION
|
7.1%
1/14
|
0.00%
0/10
|
0.00%
0/3
|
8.3%
1/12
|
0.00%
0/7
|
|
Ear and labyrinth disorders
CERUMEN IMPACTION
|
0.00%
0/14
|
10.0%
1/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Infections and infestations
CLOSTRIDIUM DIFFICILE COLITIS
|
0.00%
0/14
|
0.00%
0/10
|
33.3%
1/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Gastrointestinal disorders
CONSTIPATION
|
21.4%
3/14
|
10.0%
1/10
|
33.3%
1/3
|
41.7%
5/12
|
14.3%
1/7
|
|
Investigations
CULTURE STOOL POSITIVE
|
7.1%
1/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Metabolism and nutrition disorders
DECREASED APPETITE
|
0.00%
0/14
|
0.00%
0/10
|
0.00%
0/3
|
8.3%
1/12
|
14.3%
1/7
|
|
Metabolism and nutrition disorders
DEHYDRATION
|
14.3%
2/14
|
20.0%
2/10
|
0.00%
0/3
|
8.3%
1/12
|
28.6%
2/7
|
|
Eye disorders
EYE DISORDER
|
0.00%
0/14
|
0.00%
0/10
|
0.00%
0/3
|
16.7%
2/12
|
0.00%
0/7
|
|
Injury, poisoning and procedural complications
FALL
|
7.1%
1/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Gastrointestinal disorders
GASTROINTESTINAL PAIN
|
0.00%
0/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
14.3%
1/7
|
|
Investigations
GRANULOCYTE COUNT DECREASED
|
0.00%
0/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
14.3%
1/7
|
|
Metabolism and nutrition disorders
HYPONATRAEMIA
|
7.1%
1/14
|
0.00%
0/10
|
0.00%
0/3
|
8.3%
1/12
|
0.00%
0/7
|
|
General disorders
INFUSION SITE PAIN
|
0.00%
0/14
|
10.0%
1/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Musculoskeletal and connective tissue disorders
LOWER EXTREMITY MASS
|
7.1%
1/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Respiratory, thoracic and mediastinal disorders
NASAL CONGESTION
|
21.4%
3/14
|
10.0%
1/10
|
0.00%
0/3
|
0.00%
0/12
|
14.3%
1/7
|
|
Gastrointestinal disorders
NAUSEA
|
78.6%
11/14
|
50.0%
5/10
|
0.00%
0/3
|
58.3%
7/12
|
85.7%
6/7
|
|
Investigations
NEUTROPHIL COUNT DECREASED
|
14.3%
2/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
14.3%
1/7
|
|
General disorders
PAIN
|
14.3%
2/14
|
0.00%
0/10
|
0.00%
0/3
|
8.3%
1/12
|
0.00%
0/7
|
|
Infections and infestations
PHARYNGITIS STREPTOCOCCAL
|
0.00%
0/14
|
0.00%
0/10
|
0.00%
0/3
|
8.3%
1/12
|
0.00%
0/7
|
|
Investigations
PLATELET COUNT
|
0.00%
0/14
|
0.00%
0/10
|
0.00%
0/3
|
8.3%
1/12
|
14.3%
1/7
|
|
Psychiatric disorders
PSYCHIATRIC SYMPTOM
|
0.00%
0/14
|
0.00%
0/10
|
0.00%
0/3
|
8.3%
1/12
|
0.00%
0/7
|
|
Skin and subcutaneous tissue disorders
SKIN DISORDER
|
7.1%
1/14
|
0.00%
0/10
|
33.3%
1/3
|
16.7%
2/12
|
0.00%
0/7
|
|
Skin and subcutaneous tissue disorders
SKIN HYPERPIGMENTATION
|
7.1%
1/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Infections and infestations
STAPHYLOCOCCAL INFECTION
|
7.1%
1/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
14.3%
1/7
|
|
Blood and lymphatic system disorders
THROMBOCYTOPENIA
|
0.00%
0/14
|
10.0%
1/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Gastrointestinal disorders
TOOTHACHE
|
7.1%
1/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Gastrointestinal disorders
VOMITING
|
78.6%
11/14
|
50.0%
5/10
|
33.3%
1/3
|
75.0%
9/12
|
85.7%
6/7
|
|
Injury, poisoning and procedural complications
WRIST FRACTURE
|
7.1%
1/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Musculoskeletal and connective tissue disorders
ARTHRALGIA
|
14.3%
2/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
14.3%
1/7
|
|
Injury, poisoning and procedural complications
ARTHROPOD STING
|
0.00%
0/14
|
0.00%
0/10
|
0.00%
0/3
|
8.3%
1/12
|
0.00%
0/7
|
|
Gastrointestinal disorders
ASCITES
|
0.00%
0/14
|
0.00%
0/10
|
0.00%
0/3
|
8.3%
1/12
|
0.00%
0/7
|
|
Investigations
BLOOD CHLORIDE DECREASED
|
14.3%
2/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Investigations
BLOOD CHLORIDE INCREASED
|
14.3%
2/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Investigations
BLOOD MAGNESIUM DECREASED
|
14.3%
2/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Investigations
BLOOD TRIGLYCERIDES INCREASED
|
7.1%
1/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Investigations
BLOOD URIC ACID DECREASED
|
7.1%
1/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Gastrointestinal disorders
COLITIS
|
7.1%
1/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Ear and labyrinth disorders
DEAFNESS
|
7.1%
1/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Ear and labyrinth disorders
DEAFNESS UNILATERAL
|
7.1%
1/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Eye disorders
DIPLOPIA
|
0.00%
0/14
|
0.00%
0/10
|
0.00%
0/3
|
8.3%
1/12
|
0.00%
0/7
|
|
Skin and subcutaneous tissue disorders
ERYTHEMA
|
14.3%
2/14
|
10.0%
1/10
|
0.00%
0/3
|
16.7%
2/12
|
0.00%
0/7
|
|
Skin and subcutaneous tissue disorders
EXFOLIATIVE RASH
|
7.1%
1/14
|
0.00%
0/10
|
0.00%
0/3
|
8.3%
1/12
|
0.00%
0/7
|
|
General disorders
GAIT DISTURBANCE
|
0.00%
0/14
|
0.00%
0/10
|
0.00%
0/3
|
8.3%
1/12
|
0.00%
0/7
|
|
Renal and urinary disorders
GLYCOSURIA
|
0.00%
0/14
|
0.00%
0/10
|
0.00%
0/3
|
8.3%
1/12
|
0.00%
0/7
|
|
Gastrointestinal disorders
HAEMATOCHEZIA
|
0.00%
0/14
|
0.00%
0/10
|
0.00%
0/3
|
8.3%
1/12
|
0.00%
0/7
|
|
Gastrointestinal disorders
HAEMORRHOIDS
|
0.00%
0/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
14.3%
1/7
|
|
Blood and lymphatic system disorders
LYMPHOPENIA
|
7.1%
1/14
|
0.00%
0/10
|
0.00%
0/3
|
8.3%
1/12
|
14.3%
1/7
|
|
General disorders
MALAISE
|
7.1%
1/14
|
0.00%
0/10
|
0.00%
0/3
|
8.3%
1/12
|
0.00%
0/7
|
|
Gastrointestinal disorders
MUCOUS STOOLS
|
0.00%
0/14
|
0.00%
0/10
|
0.00%
0/3
|
8.3%
1/12
|
0.00%
0/7
|
|
Musculoskeletal and connective tissue disorders
MUSCLE SPASMS
|
0.00%
0/14
|
0.00%
0/10
|
0.00%
0/3
|
8.3%
1/12
|
14.3%
1/7
|
|
Musculoskeletal and connective tissue disorders
MUSCULOSKELETAL PAIN
|
14.3%
2/14
|
0.00%
0/10
|
0.00%
0/3
|
8.3%
1/12
|
14.3%
1/7
|
|
Musculoskeletal and connective tissue disorders
OSTEOPOROSIS
|
0.00%
0/14
|
10.0%
1/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Infections and infestations
OTITIS MEDIA
|
0.00%
0/14
|
0.00%
0/10
|
0.00%
0/3
|
16.7%
2/12
|
0.00%
0/7
|
|
Investigations
PROTEIN TOTAL DECREASED
|
7.1%
1/14
|
0.00%
0/10
|
33.3%
1/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Skin and subcutaneous tissue disorders
RASH ERYTHEMATOUS
|
0.00%
0/14
|
0.00%
0/10
|
0.00%
0/3
|
8.3%
1/12
|
0.00%
0/7
|
|
Skin and subcutaneous tissue disorders
RASH MACULO-PAPULAR
|
14.3%
2/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Injury, poisoning and procedural complications
SKIN LACERATION
|
0.00%
0/14
|
0.00%
0/10
|
0.00%
0/3
|
8.3%
1/12
|
0.00%
0/7
|
|
Skin and subcutaneous tissue disorders
SKIN ULCER
|
7.1%
1/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Ear and labyrinth disorders
TINNITUS
|
7.1%
1/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Skin and subcutaneous tissue disorders
HIRSUTISM
|
0.00%
0/14
|
0.00%
0/10
|
0.00%
0/3
|
8.3%
1/12
|
0.00%
0/7
|
|
Gastrointestinal disorders
HYPERCHLORHYDRIA
|
0.00%
0/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
14.3%
1/7
|
|
Immune system disorders
HYPERSENSITIVITY
|
0.00%
0/14
|
0.00%
0/10
|
33.3%
1/3
|
8.3%
1/12
|
0.00%
0/7
|
|
Metabolism and nutrition disorders
HYPOGLYCAEMIA
|
7.1%
1/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Metabolism and nutrition disorders
HYPOPHOSPHATAEMIA
|
7.1%
1/14
|
0.00%
0/10
|
0.00%
0/3
|
8.3%
1/12
|
0.00%
0/7
|
|
Vascular disorders
HYPOTENSION
|
21.4%
3/14
|
10.0%
1/10
|
0.00%
0/3
|
8.3%
1/12
|
14.3%
1/7
|
|
General disorders
ADVERSE EVENT
|
7.1%
1/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Investigations
ALANINE AMINOTRANSFERASE
|
7.1%
1/14
|
0.00%
0/10
|
0.00%
0/3
|
8.3%
1/12
|
0.00%
0/7
|
|
Investigations
BLOOD ALKALINE PHOSPHATASE INCREASED
|
7.1%
1/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Investigations
BLOOD BILIRUBIN
|
0.00%
0/14
|
0.00%
0/10
|
0.00%
0/3
|
8.3%
1/12
|
0.00%
0/7
|
|
Gastrointestinal disorders
CHAPPED LIPS
|
0.00%
0/14
|
10.0%
1/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Respiratory, thoracic and mediastinal disorders
COUGH
|
21.4%
3/14
|
10.0%
1/10
|
33.3%
1/3
|
25.0%
3/12
|
0.00%
0/7
|
|
Nervous system disorders
DEPRESSED LEVEL OF CONSCIOUSNESS
|
0.00%
0/14
|
10.0%
1/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Skin and subcutaneous tissue disorders
DERMATITIS CONTACT
|
0.00%
0/14
|
0.00%
0/10
|
0.00%
0/3
|
8.3%
1/12
|
0.00%
0/7
|
|
Skin and subcutaneous tissue disorders
DRY SKIN
|
21.4%
3/14
|
20.0%
2/10
|
0.00%
0/3
|
58.3%
7/12
|
57.1%
4/7
|
|
Respiratory, thoracic and mediastinal disorders
DYSPNOEA
|
14.3%
2/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Infections and infestations
EAR LOBE INFECTION
|
7.1%
1/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Vascular disorders
FLUSHING
|
7.1%
1/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
14.3%
1/7
|
|
Renal and urinary disorders
HAEMATURIA
|
0.00%
0/14
|
0.00%
0/10
|
33.3%
1/3
|
8.3%
1/12
|
0.00%
0/7
|
|
Investigations
HAEMOGLOBIN DECREASED
|
21.4%
3/14
|
0.00%
0/10
|
33.3%
1/3
|
0.00%
0/12
|
14.3%
1/7
|
|
Skin and subcutaneous tissue disorders
HAIR GROWTH ABNORMAL
|
7.1%
1/14
|
10.0%
1/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Metabolism and nutrition disorders
HYPOALBUMINAEMIA
|
0.00%
0/14
|
10.0%
1/10
|
0.00%
0/3
|
8.3%
1/12
|
0.00%
0/7
|
|
General disorders
INJECTION SITE REACTION
|
7.1%
1/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
General disorders
LOCALISED OEDEMA
|
0.00%
0/14
|
0.00%
0/10
|
0.00%
0/3
|
8.3%
1/12
|
0.00%
0/7
|
|
Gastrointestinal disorders
MELAENA
|
0.00%
0/14
|
0.00%
0/10
|
33.3%
1/3
|
0.00%
0/12
|
0.00%
0/7
|
|
General disorders
MUCOSAL INFLAMMATION
|
0.00%
0/14
|
10.0%
1/10
|
0.00%
0/3
|
8.3%
1/12
|
14.3%
1/7
|
|
Musculoskeletal and connective tissue disorders
NECK PAIN
|
21.4%
3/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
14.3%
1/7
|
|
Investigations
NEUTROPHIL COUNT
|
7.1%
1/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
14.3%
1/7
|
|
Investigations
NEUTROPHIL COUNT INCREASED
|
7.1%
1/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Skin and subcutaneous tissue disorders
PHOTOSENSITIVITY REACTION
|
0.00%
0/14
|
10.0%
1/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Renal and urinary disorders
POLLAKIURIA
|
7.1%
1/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Renal and urinary disorders
PROTEINURIA
|
0.00%
0/14
|
0.00%
0/10
|
0.00%
0/3
|
8.3%
1/12
|
0.00%
0/7
|
|
Nervous system disorders
SOMNOLENCE
|
0.00%
0/14
|
10.0%
1/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Gastrointestinal disorders
STOMATITIS
|
0.00%
0/14
|
10.0%
1/10
|
0.00%
0/3
|
16.7%
2/12
|
0.00%
0/7
|
|
Investigations
WEIGHT INCREASED
|
14.3%
2/14
|
0.00%
0/10
|
33.3%
1/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Psychiatric disorders
AGITATION
|
0.00%
0/14
|
0.00%
0/10
|
0.00%
0/3
|
8.3%
1/12
|
0.00%
0/7
|
|
Investigations
ASPARTATE AMINOTRANSFERASE
|
14.3%
2/14
|
0.00%
0/10
|
0.00%
0/3
|
8.3%
1/12
|
0.00%
0/7
|
|
Investigations
BLOOD PRESSURE INCREASED
|
0.00%
0/14
|
10.0%
1/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Investigations
BLOOD UREA DECREASED
|
7.1%
1/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Musculoskeletal and connective tissue disorders
BONE PAIN
|
7.1%
1/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Investigations
CARBON DIOXIDE INCREASED
|
7.1%
1/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Infections and infestations
CELLULITIS
|
14.3%
2/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Eye disorders
CONJUNCTIVITIS
|
0.00%
0/14
|
0.00%
0/10
|
0.00%
0/3
|
8.3%
1/12
|
0.00%
0/7
|
|
Nervous system disorders
CRANIAL NEUROPATHY
|
7.1%
1/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Ear and labyrinth disorders
EAR PAIN
|
0.00%
0/14
|
0.00%
0/10
|
0.00%
0/3
|
16.7%
2/12
|
0.00%
0/7
|
|
Infections and infestations
GASTROENTERITIS
|
14.3%
2/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Investigations
HAEMOGLOBIN
|
7.1%
1/14
|
0.00%
0/10
|
0.00%
0/3
|
8.3%
1/12
|
0.00%
0/7
|
|
Investigations
HAEMOGLOBIN ABNORMAL
|
0.00%
0/14
|
0.00%
0/10
|
33.3%
1/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Psychiatric disorders
HALLUCINATION
|
7.1%
1/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Skin and subcutaneous tissue disorders
HANGNAIL
|
7.1%
1/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Nervous system disorders
HEADACHE
|
64.3%
9/14
|
40.0%
4/10
|
66.7%
2/3
|
58.3%
7/12
|
57.1%
4/7
|
|
Metabolism and nutrition disorders
HYPOKALAEMIA
|
7.1%
1/14
|
10.0%
1/10
|
0.00%
0/3
|
0.00%
0/12
|
14.3%
1/7
|
|
Respiratory, thoracic and mediastinal disorders
HYPOXIA
|
14.3%
2/14
|
0.00%
0/10
|
33.3%
1/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Infections and infestations
INFECTION
|
14.3%
2/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
14.3%
1/7
|
|
Blood and lymphatic system disorders
LEUKOPENIA
|
7.1%
1/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Psychiatric disorders
MOOD ALTERED
|
0.00%
0/14
|
0.00%
0/10
|
0.00%
0/3
|
8.3%
1/12
|
0.00%
0/7
|
|
Musculoskeletal and connective tissue disorders
MUSCULOSKELETAL STIFFNESS
|
0.00%
0/14
|
0.00%
0/10
|
0.00%
0/3
|
8.3%
1/12
|
0.00%
0/7
|
|
Musculoskeletal and connective tissue disorders
PAIN IN JAW
|
7.1%
1/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Respiratory, thoracic and mediastinal disorders
PHARYNGEAL ERYTHEMA
|
0.00%
0/14
|
10.0%
1/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Infections and infestations
PHARYNGITIS
|
7.1%
1/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Skin and subcutaneous tissue disorders
PRURITUS GENERALISED
|
0.00%
0/14
|
10.0%
1/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Skin and subcutaneous tissue disorders
RASH
|
21.4%
3/14
|
40.0%
4/10
|
66.7%
2/3
|
41.7%
5/12
|
71.4%
5/7
|
|
Respiratory, thoracic and mediastinal disorders
RHINITIS ALLERGIC
|
0.00%
0/14
|
0.00%
0/10
|
0.00%
0/3
|
8.3%
1/12
|
0.00%
0/7
|
|
Renal and urinary disorders
URINARY RETENTION
|
7.1%
1/14
|
10.0%
1/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Eye disorders
VISION BLURRED
|
0.00%
0/14
|
0.00%
0/10
|
0.00%
0/3
|
8.3%
1/12
|
14.3%
1/7
|
|
Investigations
WHITE BLOOD CELL COUNT
|
7.1%
1/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
14.3%
1/7
|
|
Gastrointestinal disorders
ANAL FISSURE
|
0.00%
0/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
14.3%
1/7
|
|
Gastrointestinal disorders
ANAL HAEMORRHAGE
|
7.1%
1/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Investigations
BLOOD CREATININE INCREASED
|
7.1%
1/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Investigations
BLOOD LACTATE DEHYDROGENASE INCREASED
|
7.1%
1/14
|
0.00%
0/10
|
33.3%
1/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Infections and infestations
CENTRAL LINE INFECTION
|
7.1%
1/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
General disorders
CHEST PAIN
|
14.3%
2/14
|
0.00%
0/10
|
0.00%
0/3
|
8.3%
1/12
|
28.6%
2/7
|
|
Psychiatric disorders
DEPRESSED MOOD
|
7.1%
1/14
|
10.0%
1/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Psychiatric disorders
DEPRESSION
|
0.00%
0/14
|
10.0%
1/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Gastrointestinal disorders
DYSPEPSIA
|
7.1%
1/14
|
0.00%
0/10
|
0.00%
0/3
|
8.3%
1/12
|
0.00%
0/7
|
|
Gastrointestinal disorders
ENTERITIS
|
0.00%
0/14
|
0.00%
0/10
|
0.00%
0/3
|
25.0%
3/12
|
0.00%
0/7
|
|
Renal and urinary disorders
ENURESIS
|
0.00%
0/14
|
10.0%
1/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Eye disorders
EYELASH THICKENING
|
0.00%
0/14
|
0.00%
0/10
|
0.00%
0/3
|
8.3%
1/12
|
0.00%
0/7
|
|
Skin and subcutaneous tissue disorders
HYPERHIDROSIS
|
7.1%
1/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
14.3%
1/7
|
|
General disorders
INFUSION RELATED REACTION
|
7.1%
1/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Gastrointestinal disorders
LIP ULCERATION
|
0.00%
0/14
|
0.00%
0/10
|
0.00%
0/3
|
8.3%
1/12
|
0.00%
0/7
|
|
Investigations
LYMPHOCYTE COUNT
|
7.1%
1/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Gastrointestinal disorders
ORAL PAIN
|
0.00%
0/14
|
0.00%
0/10
|
0.00%
0/3
|
8.3%
1/12
|
0.00%
0/7
|
|
Skin and subcutaneous tissue disorders
PALMAR-PLANTAR ERYTHRODYSAESTHESIA SYNDROME
|
0.00%
0/14
|
0.00%
0/10
|
0.00%
0/3
|
8.3%
1/12
|
0.00%
0/7
|
|
Respiratory, thoracic and mediastinal disorders
PHARYNGOLARYNGEAL PAIN
|
28.6%
4/14
|
20.0%
2/10
|
33.3%
1/3
|
0.00%
0/12
|
14.3%
1/7
|
|
Gastrointestinal disorders
PROCTALGIA
|
7.1%
1/14
|
10.0%
1/10
|
0.00%
0/3
|
8.3%
1/12
|
0.00%
0/7
|
|
Investigations
PROTEIN TOTAL INCREASED
|
7.1%
1/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
General disorders
PYREXIA
|
35.7%
5/14
|
30.0%
3/10
|
0.00%
0/3
|
33.3%
4/12
|
28.6%
2/7
|
|
Skin and subcutaneous tissue disorders
RASH MACULAR
|
0.00%
0/14
|
0.00%
0/10
|
33.3%
1/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Respiratory, thoracic and mediastinal disorders
RHINORRHOEA
|
7.1%
1/14
|
20.0%
2/10
|
0.00%
0/3
|
16.7%
2/12
|
0.00%
0/7
|
|
Eye disorders
STRABISMUS
|
7.1%
1/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Nervous system disorders
SYNCOPE
|
0.00%
0/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
14.3%
1/7
|
|
Injury, poisoning and procedural complications
THERMAL BURN
|
0.00%
0/14
|
0.00%
0/10
|
0.00%
0/3
|
8.3%
1/12
|
0.00%
0/7
|
|
Skin and subcutaneous tissue disorders
URTICARIA
|
14.3%
2/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Gastrointestinal disorders
TONGUE ULCERATION
|
0.00%
0/14
|
10.0%
1/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Infections and infestations
VIRAL UPPER RESPIRATORY TRACT INFECTION
|
7.1%
1/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Injury, poisoning and procedural complications
WOUND COMPLICATION
|
0.00%
0/14
|
0.00%
0/10
|
0.00%
0/3
|
8.3%
1/12
|
0.00%
0/7
|
|
Gastrointestinal disorders
ABDOMINAL PAIN
|
50.0%
7/14
|
50.0%
5/10
|
33.3%
1/3
|
75.0%
9/12
|
28.6%
2/7
|
|
Investigations
ALANINE AMINOTRANSFERASE INCREASED
|
14.3%
2/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
14.3%
1/7
|
|
Skin and subcutaneous tissue disorders
ALOPECIA
|
28.6%
4/14
|
10.0%
1/10
|
0.00%
0/3
|
0.00%
0/12
|
14.3%
1/7
|
|
Musculoskeletal and connective tissue disorders
BACK PAIN
|
14.3%
2/14
|
10.0%
1/10
|
0.00%
0/3
|
8.3%
1/12
|
14.3%
1/7
|
|
Investigations
BLOOD AMYLASE DECREASED
|
7.1%
1/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Investigations
BLOOD CALCIUM DECREASED
|
7.1%
1/14
|
0.00%
0/10
|
33.3%
1/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Infections and infestations
CROUP INFECTIOUS
|
0.00%
0/14
|
10.0%
1/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Gastrointestinal disorders
DRY MOUTH
|
0.00%
0/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
14.3%
1/7
|
|
Nervous system disorders
ENCEPHALITIS
|
0.00%
0/14
|
0.00%
0/10
|
33.3%
1/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Eye disorders
EXOPHTHALMOS
|
0.00%
0/14
|
0.00%
0/10
|
0.00%
0/3
|
8.3%
1/12
|
0.00%
0/7
|
|
General disorders
FATIGUE
|
28.6%
4/14
|
40.0%
4/10
|
33.3%
1/3
|
33.3%
4/12
|
14.3%
1/7
|
|
Gastrointestinal disorders
FLATULENCE
|
14.3%
2/14
|
20.0%
2/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Metabolism and nutrition disorders
HYPERGLYCAEMIA
|
14.3%
2/14
|
10.0%
1/10
|
0.00%
0/3
|
8.3%
1/12
|
0.00%
0/7
|
|
Vascular disorders
HYPERTENSION
|
0.00%
0/14
|
0.00%
0/10
|
33.3%
1/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Nervous system disorders
HYPOAESTHESIA
|
7.1%
1/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
General disorders
IRRITABILITY
|
0.00%
0/14
|
10.0%
1/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Musculoskeletal and connective tissue disorders
MUSCULAR WEAKNESS
|
7.1%
1/14
|
0.00%
0/10
|
33.3%
1/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Musculoskeletal and connective tissue disorders
MUSCULOSKELETAL CHEST PAIN
|
14.3%
2/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Gastrointestinal disorders
PAINFUL DEFAECATION
|
7.1%
1/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Skin and subcutaneous tissue disorders
RASH PAPULAR
|
14.3%
2/14
|
10.0%
1/10
|
33.3%
1/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Respiratory, thoracic and mediastinal disorders
RESPIRATORY TRACT CONGESTION
|
7.1%
1/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Cardiac disorders
SINUS TACHYCARDIA
|
14.3%
2/14
|
0.00%
0/10
|
0.00%
0/3
|
8.3%
1/12
|
14.3%
1/7
|
|
Infections and infestations
SKIN INFECTION
|
7.1%
1/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Respiratory, thoracic and mediastinal disorders
UPPER RESPIRATORY TRACT CONGESTION
|
7.1%
1/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Gastrointestinal disorders
ABDOMINAL PAIN UPPER
|
35.7%
5/14
|
20.0%
2/10
|
0.00%
0/3
|
8.3%
1/12
|
0.00%
0/7
|
|
Metabolism and nutrition disorders
ANOREXIA
|
42.9%
6/14
|
30.0%
3/10
|
0.00%
0/3
|
50.0%
6/12
|
28.6%
2/7
|
|
Psychiatric disorders
ANXIETY
|
0.00%
0/14
|
0.00%
0/10
|
0.00%
0/3
|
16.7%
2/12
|
0.00%
0/7
|
|
General disorders
ASTHENIA
|
7.1%
1/14
|
10.0%
1/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Investigations
BLOOD BICARBONATE DECREASED
|
7.1%
1/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Investigations
BLOOD PHOSPHORUS DECREASED
|
0.00%
0/14
|
0.00%
0/10
|
33.3%
1/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Investigations
BLOOD POTASSIUM ABNORMAL
|
0.00%
0/14
|
0.00%
0/10
|
33.3%
1/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Investigations
BLOOD POTASSIUM DECREASED
|
14.3%
2/14
|
0.00%
0/10
|
33.3%
1/3
|
0.00%
0/12
|
14.3%
1/7
|
|
Cardiac disorders
BRADYCARDIA
|
7.1%
1/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
General disorders
CATHETER SITE PAIN
|
7.1%
1/14
|
0.00%
0/10
|
0.00%
0/3
|
8.3%
1/12
|
0.00%
0/7
|
|
General disorders
CATHETER SITE RASH
|
0.00%
0/14
|
0.00%
0/10
|
0.00%
0/3
|
8.3%
1/12
|
0.00%
0/7
|
|
Infections and infestations
CONJUNCTIVITIS INFECTIVE
|
7.1%
1/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Skin and subcutaneous tissue disorders
DERMATITIS ACNEIFORM
|
21.4%
3/14
|
0.00%
0/10
|
33.3%
1/3
|
8.3%
1/12
|
0.00%
0/7
|
|
Gastrointestinal disorders
DIARRHOEA
|
78.6%
11/14
|
70.0%
7/10
|
66.7%
2/3
|
83.3%
10/12
|
85.7%
6/7
|
|
Nervous system disorders
DIZZINESS
|
14.3%
2/14
|
10.0%
1/10
|
0.00%
0/3
|
8.3%
1/12
|
0.00%
0/7
|
|
Nervous system disorders
DYSGEUSIA
|
7.1%
1/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Renal and urinary disorders
DYSURIA
|
7.1%
1/14
|
10.0%
1/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Psychiatric disorders
EMOTIONAL DISORDER
|
0.00%
0/14
|
10.0%
1/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Gastrointestinal disorders
GINGIVAL BLEEDING
|
0.00%
0/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
14.3%
1/7
|
|
Blood and lymphatic system disorders
HAEMOLYSIS
|
0.00%
0/14
|
0.00%
0/10
|
0.00%
0/3
|
8.3%
1/12
|
0.00%
0/7
|
|
Nervous system disorders
HYDROCEPHALUS
|
7.1%
1/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Injury, poisoning and procedural complications
INCISION SITE COMPLICATION
|
0.00%
0/14
|
10.0%
1/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Infections and infestations
INFLUENZA
|
0.00%
0/14
|
10.0%
1/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Skin and subcutaneous tissue disorders
INGROWING NAIL
|
0.00%
0/14
|
10.0%
1/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Investigations
INTERNATIONAL NORMALISED RATIO
|
7.1%
1/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Musculoskeletal and connective tissue disorders
JOINT STIFFNESS
|
0.00%
0/14
|
0.00%
0/10
|
0.00%
0/3
|
8.3%
1/12
|
0.00%
0/7
|
|
Investigations
LYMPHOCYTE COUNT DECREASED
|
14.3%
2/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Musculoskeletal and connective tissue disorders
MYALGIA
|
14.3%
2/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Blood and lymphatic system disorders
NEUTROPENIA
|
7.1%
1/14
|
10.0%
1/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
General disorders
OEDEMA PERIPHERAL
|
0.00%
0/14
|
0.00%
0/10
|
33.3%
1/3
|
8.3%
1/12
|
0.00%
0/7
|
|
Eye disorders
PHOTOPHOBIA
|
7.1%
1/14
|
0.00%
0/10
|
0.00%
0/3
|
8.3%
1/12
|
0.00%
0/7
|
|
Investigations
PLATELET COUNT DECREASED
|
0.00%
0/14
|
0.00%
0/10
|
33.3%
1/3
|
0.00%
0/12
|
14.3%
1/7
|
|
Renal and urinary disorders
POLYURIA
|
7.1%
1/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Skin and subcutaneous tissue disorders
SKIN INDURATION
|
7.1%
1/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Respiratory, thoracic and mediastinal disorders
THROAT IRRITATION
|
7.1%
1/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Nervous system disorders
TREMOR
|
7.1%
1/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Gastrointestinal disorders
UPPER GASTROINTESTINAL HAEMORRHAGE
|
0.00%
0/14
|
0.00%
0/10
|
0.00%
0/3
|
8.3%
1/12
|
0.00%
0/7
|
|
Infections and infestations
UPPER RESPIRATORY TRACT INFECTION
|
28.6%
4/14
|
0.00%
0/10
|
33.3%
1/3
|
8.3%
1/12
|
0.00%
0/7
|
|
Investigations
VIRUS CULTURE POSITIVE
|
7.1%
1/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Investigations
WEIGHT DECREASED
|
28.6%
4/14
|
40.0%
4/10
|
33.3%
1/3
|
66.7%
8/12
|
28.6%
2/7
|
|
Respiratory, thoracic and mediastinal disorders
WHEEZING
|
0.00%
0/14
|
0.00%
0/10
|
33.3%
1/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Investigations
BLOOD ALBUMIN
|
0.00%
0/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
14.3%
1/7
|
|
Investigations
BLOOD ALBUMIN DECREASED
|
14.3%
2/14
|
0.00%
0/10
|
33.3%
1/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Investigations
BLOOD CULTURE POSITIVE
|
0.00%
0/14
|
0.00%
0/10
|
0.00%
0/3
|
8.3%
1/12
|
0.00%
0/7
|
|
Investigations
BLOOD GLUCOSE INCREASED
|
21.4%
3/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
General disorders
CATHETER RELATED COMPLICATION
|
0.00%
0/14
|
0.00%
0/10
|
33.3%
1/3
|
0.00%
0/12
|
0.00%
0/7
|
|
General disorders
CHILLS
|
0.00%
0/14
|
0.00%
0/10
|
33.3%
1/3
|
16.7%
2/12
|
0.00%
0/7
|
|
Psychiatric disorders
CONFUSIONAL STATE
|
7.1%
1/14
|
0.00%
0/10
|
33.3%
1/3
|
8.3%
1/12
|
14.3%
1/7
|
|
Nervous system disorders
CONVULSION
|
0.00%
0/14
|
10.0%
1/10
|
33.3%
1/3
|
8.3%
1/12
|
0.00%
0/7
|
|
Gastrointestinal disorders
DENTAL CARIES
|
0.00%
0/14
|
0.00%
0/10
|
0.00%
0/3
|
8.3%
1/12
|
0.00%
0/7
|
|
Respiratory, thoracic and mediastinal disorders
EPISTAXIS
|
21.4%
3/14
|
20.0%
2/10
|
0.00%
0/3
|
25.0%
3/12
|
0.00%
0/7
|
|
Blood and lymphatic system disorders
FEBRILE NEUTROPENIA
|
0.00%
0/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
14.3%
1/7
|
|
Eye disorders
GROWTH OF EYELASHES
|
21.4%
3/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
General disorders
INFUSION SITE EXTRAVASATION
|
0.00%
0/14
|
0.00%
0/10
|
0.00%
0/3
|
8.3%
1/12
|
0.00%
0/7
|
|
Nervous system disorders
LETHARGY
|
0.00%
0/14
|
0.00%
0/10
|
33.3%
1/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Infections and infestations
NAIL INFECTION
|
0.00%
0/14
|
0.00%
0/10
|
0.00%
0/3
|
8.3%
1/12
|
0.00%
0/7
|
|
Musculoskeletal and connective tissue disorders
PAIN IN EXTREMITY
|
35.7%
5/14
|
0.00%
0/10
|
0.00%
0/3
|
25.0%
3/12
|
0.00%
0/7
|
|
Skin and subcutaneous tissue disorders
PAIN OF SKIN
|
7.1%
1/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Nervous system disorders
PARAESTHESIA
|
0.00%
0/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
14.3%
1/7
|
|
Infections and infestations
PARONYCHIA
|
14.3%
2/14
|
10.0%
1/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Nervous system disorders
PERIPHERAL MOTOR NEUROPATHY
|
14.3%
2/14
|
10.0%
1/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Nervous system disorders
PERIPHERAL SENSORY NEUROPATHY
|
7.1%
1/14
|
10.0%
1/10
|
0.00%
0/3
|
8.3%
1/12
|
0.00%
0/7
|
|
Injury, poisoning and procedural complications
POST PROCEDURAL COMPLICATION
|
0.00%
0/14
|
0.00%
0/10
|
0.00%
0/3
|
8.3%
1/12
|
0.00%
0/7
|
|
Skin and subcutaneous tissue disorders
PRURITUS
|
0.00%
0/14
|
10.0%
1/10
|
33.3%
1/3
|
16.7%
2/12
|
14.3%
1/7
|
|
Infections and infestations
SKIN CANDIDA
|
0.00%
0/14
|
10.0%
1/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Skin and subcutaneous tissue disorders
SKIN EXFOLIATION
|
7.1%
1/14
|
10.0%
1/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Nervous system disorders
SPEECH DISORDER
|
0.00%
0/14
|
0.00%
0/10
|
33.3%
1/3
|
0.00%
0/12
|
0.00%
0/7
|
|
Cardiac disorders
TACHYCARDIA
|
21.4%
3/14
|
20.0%
2/10
|
0.00%
0/3
|
8.3%
1/12
|
0.00%
0/7
|
|
Investigations
WHITE BLOOD CELL COUNT DECREASED
|
14.3%
2/14
|
0.00%
0/10
|
0.00%
0/3
|
0.00%
0/12
|
0.00%
0/7
|
Additional Information
Chief Medical Officer
Eli Lilly and Company
Phone: 800-545-5979
Results disclosure agreements
- Principal investigator is a sponsor employee Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
- Publication restrictions are in place
Restriction type: OTHER