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Pazopanib Paediatric Phase II Trial Children's Oncology Group (COG) in Solid Tumors

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ClinicalTrials.gov Identifier: NCT01956669
Recruitment Status : Completed
First Posted : October 8, 2013
Results First Posted : August 12, 2020
Last Update Posted : August 12, 2020
Sponsor:
Collaborator:
Children's Oncology Group
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Solid Tumours
Intervention Drug: Pazopanib
Enrollment 57
Recruitment Details This study was conducted at 30 centers in 7 countries: Canada (2), Czech Republic (1), France (1), Hungary (1), Slovakia (1), Spain (1) and USA (23).
Pre-assignment Details 154 patients were planned to be enrolled in the study. A total of 57 patients were randomized and analyzed: cohort 1 (12), cohort 2 (11), cohort 3 (10), cohort 4 (10), cohort 5 (4), cohort 6 (4) and cohort 7 (6).
Arm/Group Title Cohort 1: Rhabdomyosarcoma (RMS) Cohort 2: Non-rhabdomyosarcomatous Soft Tissue Sarcoma (NRSTS) Cohort 3: Ewing Sarcoma/pPNET (Ewing) Cohort 4 (Osteosarcoma) Cohort 5: Measurable Neuroblastoma (mNeuroblastoma) Cohort 6: Evaluable Neuroblastoma (eNeuroblastma) Cohort 7 (Hepatoblastoma)
Hide Arm/Group Description Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles. Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles. Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles. Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles. Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles. Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles. Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Period Title: Overall Study
Started [1] 12 11 10 10 4 4 6
PK Set [2] 11 11 10 10 4 4 6
PKES Set [3] 4 0 3 0 1 1 5
Biomarker Set [4] 12 11 9 9 3 4 3
Per Protocol Set (PP Set) 9 10 6 9 4 4 5
Completed 0 0 0 0 0 0 0
Not Completed 12 11 10 10 4 4 6
Reason Not Completed
Disease Progression             12             7             7             8             4             3             5
Adverse Event             0             2             2             1             0             0             0
Physician Decision             0             2             0             0             0             1             0
Withdrawal by Subject             0             0             1             1             0             0             1
[1]
All enrolled subjects who took 1 dose of medication included in mITT and Safety Sets
[2]
All mITT subjects who had at least 1 PK sample analyzed
[3]
PK subset (received powder suspension and had at least 1 non-predose extended PK sampling)
[4]
All mITT subjects who had valid biomarker samples analyzed
Arm/Group Title Cohort 1: Rhabdomyosarcoma (RMS) Cohort 2: Non-rhabdomyosarcomatous Soft Tissue Sarcoma (NRSTS) Cohort 3: Ewing Sarcoma/pPNET (Ewing) Cohort 4 (Osteosarcoma) Cohort 5: Measurable Neuroblastoma (mNeuroblastoma) Cohort 6: Evaluable Neuroblastoma (eNeuroblastma) Cohort 7 (Hepatoblastoma) Total
Hide Arm/Group Description Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles. Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles. Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles. Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles. Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles. Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles. Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles. Total of all reporting groups
Overall Number of Baseline Participants 12 11 10 10 4 4 6 57
Hide Baseline Analysis Population Description
modified Intent-to-treat (mITT) set comprised of all subjects who received at least one dose of protocol therapy
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 12 participants 11 participants 10 participants 10 participants 4 participants 4 participants 6 participants 57 participants
9.8  (3.82) 15.7  (1.19) 12.6  (4.67) 14.1  (3.57) 9.8  (5.91) 13.0  (4.24) 5.3  (4.80) 11.9  (4.84)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 12 participants 11 participants 10 participants 10 participants 4 participants 4 participants 6 participants 57 participants
Female
5
  41.7%
4
  36.4%
3
  30.0%
1
  10.0%
3
  75.0%
3
  75.0%
5
  83.3%
24
  42.1%
Male
7
  58.3%
7
  63.6%
7
  70.0%
9
  90.0%
1
  25.0%
1
  25.0%
1
  16.7%
33
  57.9%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 12 participants 11 participants 10 participants 10 participants 4 participants 4 participants 6 participants 57 participants
White/Caucasian/European heritage 9 7 6 7 3 3 1 36
African American/African heritage 1 2 3 2 0 1 1 10
White Arabic/White North African heritage 0 0 0 0 0 0 2 2
American Indian/Alaskan native 0 1 0 0 0 0 0 1
Central/South Asian heritage 0 0 1 0 0 0 0 1
Japanese heritage 0 0 0 1 0 0 0 1
Southeast Asian heritage 0 0 0 0 0 0 1 1
Native Hawaiian/other Pacific Islander 0 1 0 0 0 0 0 1
Missing 2 0 0 0 1 0 1 4
1.Primary Outcome
Title Percentage of Participants Achieving Objective Response Rate (ORR) in Subjects' With Tumors of Primary Interest (RMS, NRSTS or Ewing Sarcoma/pPNET)
Hide Description ORR was defined as the percentage of participants achieving either a Complete Response (CR) or partial Response (PR) based on the Investigator review. The responses were assessed by CT or MRI based on Response Evaluation Criteria In Solid Tumors Criteria (RECIST1.1). CR, disappearance of all target and non-target lesions; PR, at least a 30% decrease in the disease measurement, taking as reference the disease measurement done to confirm measurable disease at study enrollment, also no new lesion or progression of any non-target measurable lesion. Confirmation was based on the disease assessment at 1 cycle or at the next scheduled visit after the initial response. Only descriptive analysis performed.
Time Frame From date of first dose of study treatment up to 55 months
Hide Outcome Measure Data
Hide Analysis Population Description
mITT Set
Arm/Group Title Cohort 1: Rhabdomyosarcoma (RMS) Cohort 2: Non-rhabdomyosarcomatous Soft Tissue Sarcoma (NRSTS) Cohort 3: Ewing Sarcoma/pPNET (Ewing)
Hide Arm/Group Description:
Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Overall Number of Participants Analyzed 12 11 10
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: Percentage of Participants
8.3
(0.4 to 33.9)
0.0
(0.0 to 23.8)
0.0
(0.0 to 25.9)
2.Secondary Outcome
Title Percentage of Participants Achieving Objective Response Rate (ORR) in Subjects' With Tumors of Secondary Interest (Osteosarcoma, mNeuroblastoma, eNeuroblastoma or Hepatoblastoma)
Hide Description ORR was defined as the percentage of participants achieving either a Complete Response (CR) or partial Response (PR) based on the Investigator review. For solid tumors with measurable diseases, such as osteosarcoma, the responses was based on RECIST1.1. CR, disappearance of all target and non target lesions; PR, at least a 30% decrease in the disease measurement, taking as reference the disease measurement done to confirm measurable disease at study enrollment, also no new lesion or progression of any non-target measurable lesion. For neuroblastoma with bone marrow response, morphology was determined by hematoxylin and eosin staining of the marrow and aspirates. For neuroblastoma MIBG+ only, the responses was assessed using Curie scale for lesion scoring; For hepatoblastoma, assessment may have included the serum AFP response, in addition to the RECIST1.1 methodology. Only descriptive analysis performed.
Time Frame From date of first dose of study treatment up to 55 months
Hide Outcome Measure Data
Hide Analysis Population Description
mITT set
Arm/Group Title Cohort 4 (Osteosarcoma) Cohort 5: Measurable Neuroblastoma (mNeuroblastoma) Cohort 6: Evaluable Neuroblastoma (eNeuroblastma) Cohort 7 (Hepatoblastoma)
Hide Arm/Group Description:
Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Overall Number of Participants Analyzed 10 4 4 6
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: Percentage of Participants
0.0
(0.0 to 25.9)
0.0
(0.0 to 52.7)
0.0
(0.0 to 52.7)
0.0
(0.0 to 39.3)
3.Secondary Outcome
Title Progression Free Survival (PFS) as Assessed by the Investigator by Cohort
Hide Description PFS was defined as the interval between the date of first dose of study medication and the earliest date of disease progression or death due to any cause. Disease progression was based on radiographic evidence, and assessments made by the investigator. According to RECIST1.1, disease progression was defined as at least a 20% increase in the sum of the disease measurements for measurable lesions, taking as reference the smallest disease measurement recorded since the start of treatment, or the appearance of one or more new lesions. For participants who did not progress or die, PFS was censored at the date of last adequate assessment or date of last adequate assessment prior to initiation of new anti-cancer therapy. Only descriptive analysis performed.
Time Frame From date of first dose of study treatment up to 59 months
Hide Outcome Measure Data
Hide Analysis Population Description
mITT set
Arm/Group Title Cohort 1: Rhabdomyosarcoma (RMS) Cohort 2: Non-rhabdomyosarcomatous Soft Tissue Sarcoma (NRSTS) Cohort 3: Ewing Sarcoma/pPNET (Ewing) Cohort 4 (Osteosarcoma) Cohort 5: Measurable Neuroblastoma (mNeuroblastoma) Cohort 6: Evaluable Neuroblastoma (eNeuroblastma) Cohort 7 (Hepatoblastoma)
Hide Arm/Group Description:
Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Overall Number of Participants Analyzed 12 11 10 10 4 4 6
Median (90% Confidence Interval)
Unit of Measure: Months
1.8
(1.0 to 1.8)
1.8
(0.3 to 13.8)
2.3
(0.2 to 13.5)
1.9
(0.5 to 5.3)
4.9
(0.8 to 6.4)
5.4
(3.6 to 24.4)
1.8
(0.5 to 1.9)
4.Secondary Outcome
Title Time to Progression (TTP) by Cohort
Hide Description The TTP was defined as the interval between the date of first dose of protocol therapy and the earliest date of disease progression or death due to disease under study. Subjects were considered to have progressive disease if they had documented progression based on radiologic assessment as determined by investigator review. According to RECIST1.1, disease progression was defined as at least a 20% increase in the sum of the disease measurements for measurable lesions, taking as reference the smallest disease measurement recorded since the start of treatment, or the appearance of one or more new lesions. Only descriptive analysis performed.
Time Frame From date of first dose of study treatment up to 59 months
Hide Outcome Measure Data
Hide Analysis Population Description
mITT set
Arm/Group Title Cohort 1: Rhabdomyosarcoma (RMS) Cohort 2: Non-rhabdomyosarcomatous Soft Tissue Sarcoma (NRSTS) Cohort 3: Ewing Sarcoma/pPNET (Ewing) Cohort 4 (Osteosarcoma) Cohort 5: Measurable Neuroblastoma (mNeuroblastoma) Cohort 6: Evaluable Neuroblastoma (eNeuroblastma) Cohort 7 (Hepatoblastoma)
Hide Arm/Group Description:
Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Overall Number of Participants Analyzed 12 11 10 10 4 4 6
Median (90% Confidence Interval)
Unit of Measure: Months
1.8
(1.0 to 1.8)
1.8
(0.3 to 13.8)
2.3
(0.2 to 13.5)
1.9
(0.5 to 5.3)
4.9
(0.8 to 6.4)
14.9
(5.4 to 24.4)
1.8
(0.5 to 1.9)
5.Secondary Outcome
Title Percentage of Participants Achieving Clinical Benefit Rate (CBR) by Cohort
Hide Description CBR was defined as the percentage of participants achieving either a confirmed complete response (CR) or confirmed partial response (PR) or Stable Disease (SD) for at least two protocol scheduled disease assessments based on RECIST1.1. CR, disappearance of all target and non-target lesions; PR, at least a 30% decrease in the disease measurement, taking as reference the disease measurement done to confirm measurable disease at study enrollment, also no new lesion or progression of any non-target measurable lesion; SD, neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease. Only descriptive analysis performed.
Time Frame From date of first dose of study treatment up to 55 months
Hide Outcome Measure Data
Hide Analysis Population Description
mITT set
Arm/Group Title Cohort 1: Rhabdomyosarcoma (RMS) Cohort 2: Non-rhabdomyosarcomatous Soft Tissue Sarcoma (NRSTS) Cohort 3: Ewing Sarcoma/pPNET (Ewing) Cohort 4 (Osteosarcoma) Cohort 5: Measurable Neuroblastoma (mNeuroblastoma) Cohort 6: Evaluable Neuroblastoma (eNeuroblastma) Cohort 7 (Hepatoblastoma)
Hide Arm/Group Description:
Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Overall Number of Participants Analyzed 12 11 10 10 4 4 6
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: Percentage of Participants
8.3
(0.4 to 33.9)
27.3
(7.9 to 56.4)
20.0
(3.7 to 50.7)
20.0
(3.7 to 50.7)
50.0
(9.8 to 90.2)
25.0
(1.3 to 75.1)
0.0
(0.0 to 39.3)
6.Secondary Outcome
Title Duration of Response (DOR) by Cohort
Hide Description DoR was defined as the time from initial response to the first documented disease progression or death due to any cause, and was determined only for those participants from the mITT population with a confirmed response (CR or PR). Only descriptive analysis performed.
Time Frame From date of first dose of study treatment up to 59 months
Hide Outcome Measure Data
Hide Analysis Population Description
mITT Set
Arm/Group Title Cohort 1: Rhabdomyosarcoma (RMS) Cohort 2: Non-rhabdomyosarcomatous Soft Tissue Sarcoma (NRSTS) Cohort 3: Ewing Sarcoma/pPNET (Ewing) Cohort 4 (Osteosarcoma) Cohort 5: Measurable Neuroblastoma (mNeuroblastoma) Cohort 6: Evaluable Neuroblastoma (eNeuroblastma) Cohort 7 (Hepatoblastoma)
Hide Arm/Group Description:
Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Overall Number of Participants Analyzed 12 11 10 10 4 4 6
Median (90% Confidence Interval)
Unit of Measure: Months
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
NA: Not estimable due to insufficient number of participants with events
7.Secondary Outcome
Title Overall Survival (OS) by Cohort
Hide Description OS was defined as the time from the first dose of the study medication until death due to any cause. Only descriptive analysis performed.
Time Frame From date of first dose of study treatment up to 61 months
Hide Outcome Measure Data
Hide Analysis Population Description
mITT Set
Arm/Group Title Cohort 1: Rhabdomyosarcoma (RMS) Cohort 2: Non-rhabdomyosarcomatous Soft Tissue Sarcoma (NRSTS) Cohort 3: Ewing Sarcoma/pPNET (Ewing) Cohort 4 (Osteosarcoma) Cohort 5: Measurable Neuroblastoma (mNeuroblastoma) Cohort 6: Evaluable Neuroblastoma (eNeuroblastma) Cohort 7 (Hepatoblastoma)
Hide Arm/Group Description:
Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Overall Number of Participants Analyzed 12 11 10 10 4 4 6
Median (90% Confidence Interval)
Unit of Measure: Months
5.6
(2.2 to 14.2)
14.6
(1.5 to 20.1)
NA [1] 
(4.3 to NA)
5.5
(1.5 to 7.0)
NA [1] 
(2.6 to NA)
5.4
(3.6 to 24.4)
5.7 [1] 
(0.6 to NA)
[1]
NA: Not estimable due to insufficient number of participants with events
8.Secondary Outcome
Title Area Under the Plasma Concentration-time Curve Calculated From Time 0 to 8 h Postdose (AUC0-8h) and Calculated to the Last Quantifiable Concentration Point (AUClast) of Pazopanib by Cohort
Hide Description AUC0-8h and AUClast were calculated using a validated liquid chromatography with tandem mass spectrometry (LC-MS/MS) and the LLOQ was 0.100 µg/mL. PK parameters were calculated from plasma concentration-time data using non-compartmental methods. Only descriptive analysis performed.
Time Frame Day 1 of Cycle 1 (0, 0.5, 1, 2, 4, 6 and 8 hours post-dose); Cycle 1 Day 15 ± 1 day (0, 0.5, 1, 2, 4, 6 and 8 hours post-dose)
Hide Outcome Measure Data
Hide Analysis Population Description
PKES set
Arm/Group Title Cohort 1: Rhabdomyosarcoma (RMS) Cohort 3: Ewing Sarcoma/pPNET (Ewing) Cohort 5: Measurable Neuroblastoma (mNeuroblastoma) Cohort 6: Evaluable Neuroblastoma (eNeuroblastma) Cohort 7 (Hepatoblastoma)
Hide Arm/Group Description:
Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Overall Number of Participants Analyzed 4 3 1 1 5
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*hr/mL
AUC0-8h (C1D1) Number Analyzed 2 participants 2 participants 0 participants 0 participants 3 participants
195
(19.0%)
214
(93.2%)
135
(60.2%)
AUC0-8h (C1D15) Number Analyzed 4 participants 2 participants 1 participants 1 participants 5 participants
388
(55.9%)
266
(36.1%)
475 [1] 
(NA%)
566 [1] 
(NA%)
229
(89.5%)
AUClast (C1D1) Number Analyzed 2 participants 3 participants 0 participants 0 participants 5 participants
194
(19.6%)
189
(65.8%)
135
(60.2%)
AUClast (C1D15) Number Analyzed 4 participants 2 participants 1 participants 1 participants 5 participants
966
(58.1%)
633
(35.4%)
1230 [1] 
(NA%)
1490 [1] 
(NA%)
607
(85.0%)
[1]
NA: Not estimable due to insufficient number of participants with events
9.Secondary Outcome
Title Observed Maximum Plasma Concentration (Cmax) of Pazopanib by Cohort
Hide Description Cmax was calculated using a validated liquid chromatography with tandem mass spectrometry (LC-MS/MS) and the LLOQ was 0.100 µg/mL. PK parameters were calculated from plasma concentration-time data using non-compartmental methods. Only descriptive analysis performed.
Time Frame Day 1 of Cycle 1 (0, 0.5, 1, 2, 4, 6 and 8 hours post-dose); Cycle 1 Day 15 ± 1 day (0, 0.5, 1, 2, 4, 6 and 8 hours post-dose)
Hide Outcome Measure Data
Hide Analysis Population Description
PKES set
Arm/Group Title Cohort 1: Rhabdomyosarcoma (RMS) Cohort 3: Ewing Sarcoma/pPNET (Ewing) Cohort 5: Measurable Neuroblastoma (mNeuroblastoma) Cohort 6: Evaluable Neuroblastoma (eNeuroblastma) Cohort 7 (Hepatoblastoma)
Hide Arm/Group Description:
Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Overall Number of Participants Analyzed 4 3 1 1 5
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
Cmax (C1D1) Number Analyzed 4 participants 3 participants 1 participants 0 participants 5 participants
34.7
(14.7%)
35.6
(75.9%)
0.0 [1] 
(NA%)
22.4
(73.7%)
Cmax (C1D15) Number Analyzed 4 participants 2 participants 1 participants 1 participants 5 participants
56.7
(53.3%)
42.0
(42.3%)
69.6 [1] 
(NA%)
80.2 [1] 
(NA%)
33.4
(95.9%)
[1]
NA: Not estimable due to insufficient number of participants with events
10.Secondary Outcome
Title Time to Reach Peak or Maximum Concentration (Tmax) of Pazopanib by Cohort
Hide Description Tmax was calculated using a validated liquid chromatography with tandem mass spectrometry (LC-MS/MS) and the LLOQ was 0.100 µg/mL. PK parameters were calculated from plasma concentration-time data using non-compartmental methods. Only descriptive analysis performed.
Time Frame Day 1 of Cycle 1 (0, 0.5, 1, 2, 4, 6 and 8 hours post-dose); Cycle 1 Day 15 ± 1 day (0, 0.5, 1, 2, 4, 6 and 8 hours post-dose)
Hide Outcome Measure Data
Hide Analysis Population Description
PKES set
Arm/Group Title Cohort 1: Rhabdomyosarcoma (RMS) Cohort 3: Ewing Sarcoma/pPNET (Ewing) Cohort 5: Measurable Neuroblastoma (mNeuroblastoma) Cohort 6: Evaluable Neuroblastoma (eNeuroblastma) Cohort 7 (Hepatoblastoma)
Hide Arm/Group Description:
Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Overall Number of Participants Analyzed 4 3 1 1 5
Median (Full Range)
Unit of Measure: Hours
Tmax (C1D1) Number Analyzed 4 participants 3 participants 1 participants 0 participants 5 participants
1
(0.00 to 2.00)
2.02
(1.00 to 5.97)
0.00
(0.00 to 0.00)
2.00
(0.00 to 6.00)
Tmax (C1D15) Number Analyzed 4 participants 2 participants 1 participants 1 participants 5 participants
2.50
(2.00 to 3.03)
1.00
(1.00 to 1.00)
3.47
(3.47 to 3.47)
3.03
(3.03 to 3.03)
3.00
(0.98 to 4.00)
11.Secondary Outcome
Title Pazopanib Steady-state Trough (Ctrough) Levels for Participants With Drug-related Grade 2 and Above Hypertension
Hide Description The relationship between toxicity (including hypertension) and pharmacokinetic parameters (pazopanib trough concentration) was analyzed. Only descriptive analysis performed.
Time Frame From date of first dose of study treatment up to 61 months
Hide Outcome Measure Data
Hide Analysis Population Description
PK set. Only participants with a drug-related grade 2 and above hypertension event included in the analysis
Arm/Group Title Cohort 1: Rhabdomyosarcoma (RMS) Cohort 2: Non-rhabdomyosarcomatous Soft Tissue Sarcoma (NRSTS) Cohort 3: Ewing Sarcoma/pPNET (Ewing) Cohort 4 (Osteosarcoma) Cohort 5: Measurable Neuroblastoma (mNeuroblastoma) Cohort 6: Evaluable Neuroblastoma (eNeuroblastma) Cohort 7 (Hepatoblastoma)
Hide Arm/Group Description:
Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Overall Number of Participants Analyzed 0 1 2 1 2 1 0
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
97.1 [1] 
(NA%)
35.7
(22.6%)
35.7 [1] 
(NA%)
38.0
(20.8%)
63.7 [1] 
(NA%)
[1]
NA: Not estimable due to insufficient number of participants with events
12.Secondary Outcome
Title Number of Participants With Genetic Alterations by Low and High Values of VEGFA and VEGFR1
Hide Description The frequency of genetic alterations observed in participants was presented by high and low baseline plasma levels for Vascular endothelial growth factor A (VEGF-A) and Vascular endothelial growth factor receptor 1 (VEGFR-1) biomarkers. The VEGFA and VEGFR1 levels above the median were classified as high and participants with median levels or below were classified as low. Only descriptive analysis performed for participants presenting with a genetic alteration.
Time Frame predose Cycle 1 Day 1, Cycle 2 Day 1
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Hide Analysis Population Description
Biomarker set. Only participants with single nucleotide variant (SNV) were included in the analysis. The FLT1 gene was found to have a single SNV in one evaluable neuroblastoma participant.
Arm/Group Title Cohort 1: Rhabdomyosarcoma (RMS) Cohort 2: Non-rhabdomyosarcomatous Soft Tissue Sarcoma (NRSTS) Cohort 3: Ewing Sarcoma/pPNET (Ewing) Cohort 4 (Osteosarcoma) Cohort 5: Measurable Neuroblastoma (mNeuroblastoma) Cohort 6: Evaluable Neuroblastoma (eNeuroblastma) Cohort 7 (Hepatoblastoma)
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Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Overall Number of Participants Analyzed 0 0 0 0 0 1 0
Measure Type: Count of Participants
Unit of Measure: Participants
VEGFA Low Number Analyzed 0 participants 0 participants 0 participants 0 participants 0 participants 1 participants 0 participants
VHL 0 0 0 0 0
0
   0.0%
0
FLT1 0 0 0 0 0
1
 100.0%
0
KDR 0 0 0 0 0
0
   0.0%
0
HIF1A 0 0 0 0 0
0
   0.0%
0
KRAS 0 0 0 0 0
0
   0.0%
0
PIK3R1 0 0 0 0 0
0
   0.0%
0
MAPK1 0 0 0 0 0
0
   0.0%
0
PLCG1 0 0 0 0 0
0
   0.0%
0
VEGFA High Number Analyzed 0 participants 0 participants 0 participants 0 participants 0 participants 0 participants 0 participants
VHL 0 0 0 0 0 0 0
FLT1 0 0 0 0 0 0 0
KDR 0 0 0 0 0 0 0
HIF1A 0 0 0 0 0 0 0
KRAS 0 0 0 0 0 0 0
PIK3R1 0 0 0 0 0 0 0
MAPK1 0 0 0 0 0 0 0
PLCG1 0 0 0 0 0 0 0
VEGFR1 Low Number Analyzed 0 participants 0 participants 0 participants 0 participants 0 participants 0 participants 0 participants
VHL 0 0 0 0 0 0 0
FLT1 0 0 0 0 0 0 0
KDR 0 0 0 0 0 0 0
HIF1A 0 0 0 0 0 0 0
KRAS 0 0 0 0 0 0 0
PIK3R1 0 0 0 0 0 0 0
MAPK1 0 0 0 0 0 0 0
PLCG1 0 0 0 0 0 0 0
VEGFR1 High Number Analyzed 0 participants 0 participants 0 participants 0 participants 0 participants 1 participants 0 participants
VHL 0 0 0 0 0
0
   0.0%
0
FLT1 0 0 0 0 0
1
 100.0%
0
KDR 0 0 0 0 0
0
   0.0%
0
HIF1A 0 0 0 0 0
0
   0.0%
0
KRAS 0 0 0 0 0
0
   0.0%
0
PIK3R1 0 0 0 0 0
0
   0.0%
0
MAPK1 0 0 0 0 0
0
   0.0%
0
PLCG1 0 0 0 0 0
0
   0.0%
0
13.Secondary Outcome
Title Summary for Plasma Biomarkers Levels on Cycle 1 Day 1 and Cycle 2 Day 1 by Cohort
Hide Description The following biomarker parameters were analyzed: proto-oncogene c-KIT (c-KIT), Fibroblast growth factor (FGF), Placental growth factor PGF), Angiopoietin-1 receptor (TIE2), Vascular endothelial growth factor A (VEGF-A), Vascular endothelial growth factor C (VEGF-C), Vascular endothelial growth factor D (VEGF-D), Vascular endothelial growth factor receptor 1 (VEGFR-1) and Vascular endothelial growth factor receptor 2 (VEGFR-2)). Only descriptive analysis performed.
Time Frame predose Cycle 1 Day 1, Cycle 2 Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
Biomarker set
Arm/Group Title Cohort 1: Rhabdomyosarcoma (RMS) Cohort 2: Non-rhabdomyosarcomatous Soft Tissue Sarcoma (NRSTS) Cohort 3: Ewing Sarcoma/pPNET (Ewing) Cohort 4 (Osteosarcoma) Cohort 5: Measurable Neuroblastoma (mNeuroblastoma) Cohort 6: Evaluable Neuroblastoma (eNeuroblastma) Cohort 7 (Hepatoblastoma)
Hide Arm/Group Description:
Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Overall Number of Participants Analyzed 12 11 9 9 3 4 3
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: picogram/milliliter (pg/mL)
c-KIT (C1D1) Number Analyzed 12 participants 10 participants 9 participants 8 participants 2 participants 3 participants 3 participants
139522.4
(29.4%)
142526.9
(24.3%)
135024.5
(25.9%)
137317.7
(23.9%)
142630.1
(18.0%)
113596.9
(26.6%)
119921.9
(30.6%)
c-KIT (C2D1) Number Analyzed 6 participants 5 participants 3 participants 4 participants 2 participants 2 participants 1 participants
110154.0
(14.1%)
99962.7
(8.2%)
94307.1
(15.1%)
99989.6
(18.9%)
121497.7
(23.0%)
71216.5
(2.0%)
154558.2 [1] 
(NA%)
FGF (C1D1) Number Analyzed 3 participants 3 participants 2 participants 2 participants 0 participants 1 participants 0 participants
7.8
(63.1%)
6.9
(71.1%)
8.3
(59.1%)
5.9
(6.0%)
13.5 [1] 
(NA%)
FGF (C2D1) Number Analyzed 4 participants 1 participants 1 participants 0 participants 1 participants 0 participants 0 participants
15.1
(68.9%)
6.2 [1] 
(NA%)
5.1 [1] 
(NA%)
6.6 [1] 
(NA%)
PGF (C1D1) Number Analyzed 12 participants 9 participants 7 participants 8 participants 2 participants 2 participants 3 participants
19.6
(245.7%)
8.9
(27.6%)
9.4
(36.9%)
10.5
(37.0%)
9.3
(6.2%)
13.7
(126.6%)
8.6
(29.7%)
PGF (C2D1) Number Analyzed 6 participants 5 participants 3 participants 4 participants 2 participants 2 participants 1 participants
54.6
(259.4%)
27.8
(74.9%)
37.4
(82.9%)
63.2
(113.8%)
30.3
(300.5%)
225.2
(840.1%)
39.4 [1] 
(NA%)
TIE2 (C1D1) Number Analyzed 12 participants 10 participants 9 participants 8 participants 2 participants 3 participants 3 participants
8086.8
(26.5%)
8180.0
(25.0%)
7280.6
(15.6%)
8574.9
(7.7%)
7439.8
(4.6%)
8179.2
(30.0%)
7842.2
(18.3%)
TIE2 (C2D1) Number Analyzed 6 participants 5 participants 3 participants 4 participants 2 participants 2 participants 1 participants
8340.1
(11.5%)
7788.8
(11.5%)
7650.6
(22.7%)
7894.1
(17.4%)
8026.6
(28.2%)
6824.4
(32.0%)
8540.0 [1] 
(NA%)
VEGF-A (C1D1) Number Analyzed 12 participants 10 participants 9 participants 8 participants 2 participants 3 participants 3 participants
63.8
(133.8%)
46.1
(66.1%)
74.0
(98.0%)
82.9
(62.0%)
48.8
(39.0%)
62.2
(268.3%)
129.3
(46.6%)
VEGF-A (C2D1) Number Analyzed 6 participants 5 participants 3 participants 4 participants 2 participants 2 participants 1 participants
123.3
(140.6%)
77.2
(166.8%)
171.8
(126.0%)
179.4
(98.7%)
219.3
(40.4%)
1057.5
(750.0%)
208.9 [1] 
(NA%)
VEGF-C (C1D1) Number Analyzed 2 participants 2 participants 0 participants 0 participants 0 participants 0 participants 0 participants
121.4
(1.6%)
152.6
(84.7%)
VEGF-C (C2D1) Number Analyzed 1 participants 1 participants 0 participants 0 participants 0 participants 0 participants 0 participants
105.9 [1] 
(NA%)
339.9 [1] 
(NA%)
VEGF-D (C1D1) Number Analyzed 12 participants 10 participants 9 participants 8 participants 2 participants 3 participants 3 participants
354.2
(54.6%)
372.3
(20.5%)
394.6
(21.6%)
375.4
(43.9%)
645.4
(108.7%)
351.7
(12.1%)
370.0
(75.9%)
VEGF-D (C2D1) Number Analyzed 6 participants 5 participants 3 participants 4 participants 2 participants 2 participants 1 participants
434.6
(77.4%)
501.8
(43.0%)
448.6
(16.9%)
551.7
(14.4%)
501.4
(50.1%)
791.4
(51.1%)
400.4 [1] 
(NA%)
VEGFR-1 (C1D1) Number Analyzed 12 participants 10 participants 9 participants 8 participants 2 participants 3 participants 3 participants
394.5
(292.3%)
175.7
(174.4%)
224.4
(121.7%)
134.6
(113.7%)
95.8
(42.9%)
367.5
(130.8%)
173.4
(109.6%)
VEGFR-1 (C2D1) Number Analyzed 6 participants 5 participants 3 participants 4 participants 2 participants 2 participants 1 participants
87.5
(98.5%)
534.3
(709.9%)
93.8
(121.1%)
140.0
(231.3%)
69.4
(4.9%)
76.4
(14.6%)
1811.6 [1] 
(NA%)
VEGFR-2 (C1D1) Number Analyzed 12 participants 10 participants 9 participants 8 participants 2 participants 3 participants 3 participants
31451.9
(22.6%)
31745.8
(20.6%)
33724.8
(15.8%)
34993.1
(17.6%)
31682.1
(12.1%)
39342.8
(14.7%)
30780.5
(6.0%)
VEGFR-2 (C2D1) Number Analyzed 6 participants 5 participants 3 participants 4 participants 2 participants 2 participants 1 participants
25099.6
(22.9%)
23059.9
(21.6%)
23502.8
(1.0%)
22154.3
(15.1%)
25385.9
(42.9%)
13621.6
(68.5%)
26266.9 [1] 
(NA%)
[1]
NA: Not estimable due to insufficient number of participants with events
14.Secondary Outcome
Title Summary for Change From Baseline Levels of Plasma Biomarkers by High and Low Pazopanib Steady State Trough Concentration and Cohort
Hide Description Participants with steady state trough concentration median levels for the following biomarker parameters (proto-oncogene c-KIT (c-KIT), Fibroblast growth factor (FGF), Placental growth factor PGF), Angiopoietin-1 receptor (TIE2), Vascular endothelial growth factor A (VEGF-A), Vascular endothelial growth factor C (VEGF-C), Vascular endothelial growth factor D (VEGF-D), Vascular endothelial growth factor receptor 1 (VEGFR-1) and Vascular endothelial growth factor receptor 2 (VEGFR-2)) above the median levels were classified as high or below median levels were classified as low. Only descriptive analysis performed.
Time Frame predose Cycle 1 Day 1, Cycle 2 Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
Biomarker set. Only patient with steady state trough plasma Pazopanib concentration included in the analysis.
Arm/Group Title Cohort 1: Rhabdomyosarcoma (RMS) Cohort 2: Non-rhabdomyosarcomatous Soft Tissue Sarcoma (NRSTS) Cohort 3: Ewing Sarcoma/pPNET (Ewing) Cohort 4 (Osteosarcoma) Cohort 5: Measurable Neuroblastoma (mNeuroblastoma) Cohort 6: Evaluable Neuroblastoma (eNeuroblastma) Cohort 7 (Hepatoblastoma)
Hide Arm/Group Description:
Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Overall Number of Participants Analyzed 12 11 9 9 3 4 3
Mean (Standard Deviation)
Unit of Measure: picogram/milliliter (pg/mL)
c-KIT high trough concentration Number Analyzed 0 participants 0 participants 1 participants 1 participants 0 participants 1 participants 0 participants
-76081.1 [1]   (NA) -40512.6 [1]   (NA) -51199.4 [1]   (NA)
c-KIT low trough concentration Number Analyzed 1 participants 1 participants 0 participants 1 participants 0 participants 1 participants 0 participants
-13480.5 [1]   (NA) -44973.7 [1]   (NA) -48764.1 [1]   (NA) -35678.6 [1]   (NA)
FGF high trough concentration Number Analyzed 0 participants 0 participants 1 participants 0 participants 0 participants 0 participants 0 participants
-7.0 [1]   (NA)
FGF low trough concentration Number Analyzed 0 participants 0 participants 0 participants 0 participants 0 participants 0 participants 0 participants
PGF high trough concentration Number Analyzed 0 participants 0 participants 1 participants 1 participants 0 participants 1 participants 0 participants
78.3 [1]   (NA) 15.6 [1]   (NA) 45.4 [1]   (NA)
PGF low trough concentration Number Analyzed 0 participants 1 participants 0 participants 1 participants 0 participants 0 participants 0 participants
5.6 [1]   (NA) 28.3 [1]   (NA)
TIE2 high trough concentration Number Analyzed 0 participants 0 participants 1 participants 1 participants 0 participants 1 participants 0 participants
2553.0 [1]   (NA) -509.4 [1]   (NA) -2708.2 [1]   (NA)
TIE2 low trough concentration Number Analyzed 1 participants 1 participants 0 participants 1 participants 0 participants 1 participants 0 participants
1212.4 [1]   (NA) -1514.9 [1]   (NA) -918.4 [1]   (NA) -473.0 [1]   (NA)
VEGF-A high trough concentration Number Analyzed 0 participants 0 participants 1 participants 1 participants 0 participants 1 participants 0 participants
358.8 [1]   (NA) 34.3 [1]   (NA) -73.3 [1]   (NA)
VEGF-A low trough concentration Number Analyzed 1 participants 1 participants 0 participants 1 participants 0 participants 1 participants 0 participants
2436.6 [1]   (NA) 18.5 [1]   (NA) 52.3 [1]   (NA) 39.7 [1]   (NA)
VEGF-C high trough concentration Number Analyzed 0 participants 0 participants 0 participants 0 participants 0 participants 0 participants 0 participants
VEGF-C low trough concentration Number Analyzed 0 participants 0 participants 0 participants 0 participants 0 participants 0 participants 0 participants
VEGF-D high trough concentration Number Analyzed 0 participants 0 participants 1 participants 1 participants 0 participants 1 participants 0 participants
88.0 [1]   (NA) 139.7 [1]   (NA) 187.5 [1]   (NA)
VEGF-D low trough concentration Number Analyzed 1 participants 1 participants 0 participants 1 participants 0 participants 1 participants 0 participants
423.2 [1]   (NA) 44.1 [1]   (NA) 153.5 [1]   (NA) 90.8 [1]   (NA)
VEGFR-1 high trough concentration Number Analyzed 0 participants 0 participants 1 participants 1 participants 0 participants 1 participants 0 participants
-217.5 [1]   (NA) 955.6 [1]   (NA) -49.7 [1]   (NA)
VEGFR-1 low trough concentration Number Analyzed 1 participants 1 participants 0 participants 1 participants 0 participants 1 participants 0 participants
484.1 [1]   (NA) -67.2 [1]   (NA) -7.7 [1]   (NA) -741.3 [1]   (NA)
VEGFR-2 high trough concentration Number Analyzed 0 participants 0 participants 1 participants 1 participants 0 participants 1 participants 0 participants
-2620.0 [1]   (NA) -16136.9 [1]   (NA) -16838.7 [1]   (NA)
VEGFR-2 low trough concentration Number Analyzed 1 participants 1 participants 0 participants 1 participants 0 participants 1 participants 0 participants
-12130.8 [1]   (NA) -7795.4 [1]   (NA) -8588.1 [1]   (NA) -10529.6 [1]   (NA)
[1]
NA: Not estimable due to insufficient number of participants with events
Time Frame Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days.
Adverse Event Reporting Description

Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment.

Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).

 
Arm/Group Title Cohort 1: Rhabdomyosarcoma (RMS) Cohort 2: Nonrhabdomyosarcomatous Soft Tissue Sarcoma (NRSTS) Cohort 3: Ewing Sarcoma/pPNET (Ewing) Cohort 4 (Osteosarcoma) Cohort 5: Measurable Neuroblastoma (mNeuroblastoma) Cohort 6: Evaluable Neuroblastoma (eNeuroblastma) Cohort 7 (Hepatoblastoma) All Subjects
Hide Arm/Group Description Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles. Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles. Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles. Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles. Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles. Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles. Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles. Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m^2/dose or as a powder in suspension at a dose of 225 mg/m^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m^2/dose was not tolerated (>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
All-Cause Mortality
Cohort 1: Rhabdomyosarcoma (RMS) Cohort 2: Nonrhabdomyosarcomatous Soft Tissue Sarcoma (NRSTS) Cohort 3: Ewing Sarcoma/pPNET (Ewing) Cohort 4 (Osteosarcoma) Cohort 5: Measurable Neuroblastoma (mNeuroblastoma) Cohort 6: Evaluable Neuroblastoma (eNeuroblastma) Cohort 7 (Hepatoblastoma) All Subjects
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   3/12 (25.00%)   0/11 (0.00%)   1/10 (10.00%)   3/10 (30.00%)   0/4 (0.00%)   1/4 (25.00%)   1/6 (16.67%)   9/57 (15.79%) 
Hide Serious Adverse Events
Cohort 1: Rhabdomyosarcoma (RMS) Cohort 2: Nonrhabdomyosarcomatous Soft Tissue Sarcoma (NRSTS) Cohort 3: Ewing Sarcoma/pPNET (Ewing) Cohort 4 (Osteosarcoma) Cohort 5: Measurable Neuroblastoma (mNeuroblastoma) Cohort 6: Evaluable Neuroblastoma (eNeuroblastma) Cohort 7 (Hepatoblastoma) All Subjects
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   2/12 (16.67%)   5/11 (45.45%)   3/10 (30.00%)   3/10 (30.00%)   0/4 (0.00%)   1/4 (25.00%)   3/6 (50.00%)   17/57 (29.82%) 
Blood and lymphatic system disorders                 
Thrombocytopenia  1  0/12 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  1/4 (25.00%)  0/6 (0.00%)  1/57 (1.75%) 
Cardiac disorders                 
Cardiopulmonary failure  1  0/12 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  1/4 (25.00%)  0/6 (0.00%)  1/57 (1.75%) 
Left ventricular dysfunction  1  0/12 (0.00%)  1/11 (9.09%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/57 (1.75%) 
Gastrointestinal disorders                 
Diarrhoea  1  0/12 (0.00%)  1/11 (9.09%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/57 (1.75%) 
Rectal haemorrhage  1  0/12 (0.00%)  1/11 (9.09%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/57 (1.75%) 
General disorders                 
Pain  1  1/12 (8.33%)  0/11 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/57 (1.75%) 
Infections and infestations                 
Cellulitis  1  0/12 (0.00%)  1/11 (9.09%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/57 (1.75%) 
Sepsis  1  0/12 (0.00%)  0/11 (0.00%)  1/10 (10.00%)  0/10 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/57 (1.75%) 
Skin infection  1  0/12 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  1/10 (10.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/57 (1.75%) 
Upper respiratory tract infection  1  0/12 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  1/57 (1.75%) 
Wound infection  1  0/12 (0.00%)  1/11 (9.09%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/57 (1.75%) 
Injury, poisoning and procedural complications                 
Wound dehiscence  1  0/12 (0.00%)  1/11 (9.09%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/57 (1.75%) 
Investigations                 
Blood creatinine increased  1  1/12 (8.33%)  0/11 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/57 (1.75%) 
Gamma-glutamyltransferase increased  1  0/12 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  1/57 (1.75%) 
Hepatic enzyme increased  1  0/12 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  1/10 (10.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/57 (1.75%) 
Metabolism and nutrition disorders                 
Dehydration  1  0/12 (0.00%)  1/11 (9.09%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  2/57 (3.51%) 
Musculoskeletal and connective tissue disorders                 
Muscular weakness  1  0/12 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  1/10 (10.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/57 (1.75%) 
Myalgia  1  0/12 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  1/10 (10.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/57 (1.75%) 
Pain in extremity  1  0/12 (0.00%)  0/11 (0.00%)  2/10 (20.00%)  0/10 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  2/57 (3.51%) 
Nervous system disorders                 
Intracranial pressure increased  1  0/12 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  1/57 (1.75%) 
Respiratory, thoracic and mediastinal disorders                 
Pleural effusion  1  1/12 (8.33%)  0/11 (0.00%)  0/10 (0.00%)  1/10 (10.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  2/57 (3.51%) 
Pneumothorax  1  0/12 (0.00%)  1/11 (9.09%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/57 (1.75%) 
1
Term from vocabulary, MedDRA (22.0)
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Cohort 1: Rhabdomyosarcoma (RMS) Cohort 2: Nonrhabdomyosarcomatous Soft Tissue Sarcoma (NRSTS) Cohort 3: Ewing Sarcoma/pPNET (Ewing) Cohort 4 (Osteosarcoma) Cohort 5: Measurable Neuroblastoma (mNeuroblastoma) Cohort 6: Evaluable Neuroblastoma (eNeuroblastma) Cohort 7 (Hepatoblastoma) All Subjects
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   12/12 (100.00%)   11/11 (100.00%)   10/10 (100.00%)   10/10 (100.00%)   4/4 (100.00%)   4/4 (100.00%)   6/6 (100.00%)   57/57 (100.00%) 
Blood and lymphatic system disorders                 
Anaemia  1  3/12 (25.00%)  1/11 (9.09%)  0/10 (0.00%)  3/10 (30.00%)  2/4 (50.00%)  1/4 (25.00%)  2/6 (33.33%)  12/57 (21.05%) 
Leukopenia  1  0/12 (0.00%)  1/11 (9.09%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  1/4 (25.00%)  0/6 (0.00%)  2/57 (3.51%) 
Lymphopenia  1  0/12 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  1/10 (10.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/57 (1.75%) 
Neutropenia  1  2/12 (16.67%)  0/11 (0.00%)  1/10 (10.00%)  2/10 (20.00%)  0/4 (0.00%)  1/4 (25.00%)  0/6 (0.00%)  6/57 (10.53%) 
Thrombocytopenia  1  0/12 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  1/10 (10.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/57 (1.75%) 
Cardiac disorders                 
Sinus bradycardia  1  1/12 (8.33%)  0/11 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/57 (1.75%) 
Sinus tachycardia  1  0/12 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  1/10 (10.00%)  1/4 (25.00%)  0/4 (0.00%)  1/6 (16.67%)  3/57 (5.26%) 
Supraventricular extrasystoles  1  0/12 (0.00%)  1/11 (9.09%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/57 (1.75%) 
Tachycardia  1  0/12 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  1/57 (1.75%) 
Ear and labyrinth disorders                 
Cerumen impaction  1  1/12 (8.33%)  0/11 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/57 (1.75%) 
Deafness bilateral  1  1/12 (8.33%)  0/11 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/57 (1.75%) 
Vertigo  1  0/12 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  1/57 (1.75%) 
Endocrine disorders                 
Hypothyroidism  1  2/12 (16.67%)  2/11 (18.18%)  3/10 (30.00%)  2/10 (20.00%)  0/4 (0.00%)  2/4 (50.00%)  0/6 (0.00%)  11/57 (19.30%) 
Eye disorders                 
Conjunctival haemorrhage  1  0/12 (0.00%)  0/11 (0.00%)  1/10 (10.00%)  0/10 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/57 (1.75%) 
Erythema of eyelid  1  0/12 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  1/57 (1.75%) 
Eye pain  1  1/12 (8.33%)  0/11 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/57 (1.75%) 
Eye pruritus  1  0/12 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  0/6 (0.00%)  1/57 (1.75%) 
Eyelash discolouration  1  0/12 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  0/6 (0.00%)  1/57 (1.75%) 
Vision blurred  1  1/12 (8.33%)  1/11 (9.09%)  2/10 (20.00%)  0/10 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  4/57 (7.02%) 
Gastrointestinal disorders                 
Abdominal distension  1  1/12 (8.33%)  0/11 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/57 (1.75%) 
Abdominal pain  1  5/12 (41.67%)  4/11 (36.36%)  1/10 (10.00%)  4/10 (40.00%)  2/4 (50.00%)  1/4 (25.00%)  2/6 (33.33%)  19/57 (33.33%) 
Abdominal pain upper  1  0/12 (0.00%)  0/11 (0.00%)  2/10 (20.00%)  0/10 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  2/57 (3.51%) 
Cheilitis  1  0/12 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  1/4 (25.00%)  0/6 (0.00%)  1/57 (1.75%) 
Constipation  1  2/12 (16.67%)  0/11 (0.00%)  1/10 (10.00%)  2/10 (20.00%)  0/4 (0.00%)  1/4 (25.00%)  2/6 (33.33%)  8/57 (14.04%) 
Diarrhoea  1  3/12 (25.00%)  3/11 (27.27%)  4/10 (40.00%)  2/10 (20.00%)  2/4 (50.00%)  2/4 (50.00%)  1/6 (16.67%)  17/57 (29.82%) 
Dyspepsia  1  2/12 (16.67%)  0/11 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  2/57 (3.51%) 
Flatulence  1  1/12 (8.33%)  0/11 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/57 (1.75%) 
Frequent bowel movements  1  0/12 (0.00%)  1/11 (9.09%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/57 (1.75%) 
Gastrooesophageal reflux disease  1  0/12 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  1/4 (25.00%)  0/6 (0.00%)  1/57 (1.75%) 
Haematochezia  1  0/12 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  1/4 (25.00%)  0/6 (0.00%)  1/57 (1.75%) 
Nausea  1  4/12 (33.33%)  1/11 (9.09%)  5/10 (50.00%)  3/10 (30.00%)  2/4 (50.00%)  2/4 (50.00%)  3/6 (50.00%)  20/57 (35.09%) 
Oral dysaesthesia  1  0/12 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  0/6 (0.00%)  1/57 (1.75%) 
Oral pain  1  0/12 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  1/4 (25.00%)  1/4 (25.00%)  0/6 (0.00%)  2/57 (3.51%) 
Toothache  1  0/12 (0.00%)  1/11 (9.09%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/57 (1.75%) 
Vomiting  1  8/12 (66.67%)  0/11 (0.00%)  2/10 (20.00%)  3/10 (30.00%)  2/4 (50.00%)  1/4 (25.00%)  4/6 (66.67%)  20/57 (35.09%) 
General disorders                 
Asthenia  1  0/12 (0.00%)  1/11 (9.09%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  1/4 (25.00%)  0/6 (0.00%)  2/57 (3.51%) 
Fatigue  1  4/12 (33.33%)  3/11 (27.27%)  4/10 (40.00%)  2/10 (20.00%)  0/4 (0.00%)  2/4 (50.00%)  2/6 (33.33%)  17/57 (29.82%) 
Feeling jittery  1  1/12 (8.33%)  0/11 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/57 (1.75%) 
Gait disturbance  1  1/12 (8.33%)  0/11 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  0/6 (0.00%)  2/57 (3.51%) 
Influenza like illness  1  0/12 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  2/10 (20.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  2/57 (3.51%) 
Nodule  1  1/12 (8.33%)  0/11 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/57 (1.75%) 
Non-cardiac chest pain  1  0/12 (0.00%)  3/11 (27.27%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  3/57 (5.26%) 
Oedema peripheral  1  0/12 (0.00%)  0/11 (0.00%)  1/10 (10.00%)  1/10 (10.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  2/57 (3.51%) 
Pain  1  0/12 (0.00%)  1/11 (9.09%)  1/10 (10.00%)  2/10 (20.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  4/57 (7.02%) 
Peripheral swelling  1  0/12 (0.00%)  1/11 (9.09%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/57 (1.75%) 
Pyrexia  1  5/12 (41.67%)  1/11 (9.09%)  2/10 (20.00%)  3/10 (30.00%)  1/4 (25.00%)  0/4 (0.00%)  4/6 (66.67%)  16/57 (28.07%) 
Hepatobiliary disorders                 
Hepatic steatosis  1  0/12 (0.00%)  1/11 (9.09%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/57 (1.75%) 
Hyperbilirubinaemia  1  0/12 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  1/4 (25.00%)  0/6 (0.00%)  1/57 (1.75%) 
Infections and infestations                 
Folliculitis  1  0/12 (0.00%)  1/11 (9.09%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/57 (1.75%) 
Nasopharyngitis  1  0/12 (0.00%)  1/11 (9.09%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/57 (1.75%) 
Otitis media acute  1  1/12 (8.33%)  0/11 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/57 (1.75%) 
Pharyngitis  1  0/12 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  1/10 (10.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/57 (1.75%) 
Rhinitis  1  1/12 (8.33%)  0/11 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/57 (1.75%) 
Sinusitis  1  1/12 (8.33%)  0/11 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/57 (1.75%) 
Upper respiratory tract infection  1  3/12 (25.00%)  1/11 (9.09%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  4/57 (7.02%) 
Urinary tract infection  1  1/12 (8.33%)  1/11 (9.09%)  1/10 (10.00%)  0/10 (0.00%)  0/4 (0.00%)  1/4 (25.00%)  0/6 (0.00%)  4/57 (7.02%) 
Injury, poisoning and procedural complications                 
Contusion  1  0/12 (0.00%)  2/11 (18.18%)  0/10 (0.00%)  0/10 (0.00%)  1/4 (25.00%)  2/4 (50.00%)  0/6 (0.00%)  5/57 (8.77%) 
Fall  1  0/12 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  1/4 (25.00%)  0/6 (0.00%)  1/57 (1.75%) 
Gastrostomy tube site complication  1  1/12 (8.33%)  0/11 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/57 (1.75%) 
Procedural pain  1  0/12 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  1/57 (1.75%) 
Tongue injury  1  0/12 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  0/6 (0.00%)  1/57 (1.75%) 
Wound  1  0/12 (0.00%)  0/11 (0.00%)  1/10 (10.00%)  0/10 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/57 (1.75%) 
Wound complication  1  0/12 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  1/10 (10.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/57 (1.75%) 
Investigations                 
Activated partial thromboplastin time prolonged  1  0/12 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  1/10 (10.00%)  0/4 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  2/57 (3.51%) 
Alanine aminotransferase increased  1  3/12 (25.00%)  0/11 (0.00%)  3/10 (30.00%)  4/10 (40.00%)  0/4 (0.00%)  1/4 (25.00%)  3/6 (50.00%)  14/57 (24.56%) 
Amylase increased  1  0/12 (0.00%)  0/11 (0.00%)  1/10 (10.00%)  1/10 (10.00%)  0/4 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  3/57 (5.26%) 
Aspartate aminotransferase increased  1  4/12 (33.33%)  0/11 (0.00%)  3/10 (30.00%)  3/10 (30.00%)  1/4 (25.00%)  1/4 (25.00%)  4/6 (66.67%)  16/57 (28.07%) 
Blood alkaline phosphatase  1  1/12 (8.33%)  0/11 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/57 (1.75%) 
Blood alkaline phosphatase increased  1  0/12 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  1/10 (10.00%)  0/4 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  2/57 (3.51%) 
Blood bilirubin increased  1  0/12 (0.00%)  0/11 (0.00%)  1/10 (10.00%)  1/10 (10.00%)  1/4 (25.00%)  0/4 (0.00%)  1/6 (16.67%)  4/57 (7.02%) 
Blood creatinine increased  1  1/12 (8.33%)  0/11 (0.00%)  1/10 (10.00%)  1/10 (10.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  3/57 (5.26%) 
Blood thyroid stimulating hormone increased  1  0/12 (0.00%)  3/11 (27.27%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  3/57 (5.26%) 
Blood urea increased  1  0/12 (0.00%)  0/11 (0.00%)  1/10 (10.00%)  0/10 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/57 (1.75%) 
Carbon dioxide decreased  1  1/12 (8.33%)  0/11 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/57 (1.75%) 
Cardiac murmur  1  0/12 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  1/10 (10.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/57 (1.75%) 
Creatinine urine increased  1  0/12 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  0/6 (0.00%)  1/57 (1.75%) 
Ejection fraction decreased  1  0/12 (0.00%)  1/11 (9.09%)  1/10 (10.00%)  1/10 (10.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  3/57 (5.26%) 
Electrocardiogram QT prolonged  1  0/12 (0.00%)  0/11 (0.00%)  1/10 (10.00%)  0/10 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/57 (1.75%) 
Gamma-glutamyltransferase increased  1  0/12 (0.00%)  0/11 (0.00%)  1/10 (10.00%)  0/10 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  3/6 (50.00%)  4/57 (7.02%) 
Haemoglobin increased  1  1/12 (8.33%)  0/11 (0.00%)  0/10 (0.00%)  1/10 (10.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  2/57 (3.51%) 
International normalised ratio increased  1  0/12 (0.00%)  0/11 (0.00%)  1/10 (10.00%)  0/10 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/57 (1.75%) 
Lipase increased  1  1/12 (8.33%)  0/11 (0.00%)  1/10 (10.00%)  1/10 (10.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  3/57 (5.26%) 
Lymphocyte count decreased  1  2/12 (16.67%)  0/11 (0.00%)  0/10 (0.00%)  1/10 (10.00%)  1/4 (25.00%)  0/4 (0.00%)  1/6 (16.67%)  5/57 (8.77%) 
Lymphocyte count increased  1  0/12 (0.00%)  0/11 (0.00%)  1/10 (10.00%)  0/10 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/57 (1.75%) 
Monocyte count increased  1  0/12 (0.00%)  0/11 (0.00%)  1/10 (10.00%)  0/10 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/57 (1.75%) 
Neutrophil count decreased  1  2/12 (16.67%)  2/11 (18.18%)  1/10 (10.00%)  2/10 (20.00%)  1/4 (25.00%)  0/4 (0.00%)  2/6 (33.33%)  10/57 (17.54%) 
Platelet count decreased  1  4/12 (33.33%)  1/11 (9.09%)  2/10 (20.00%)  5/10 (50.00%)  1/4 (25.00%)  1/4 (25.00%)  2/6 (33.33%)  16/57 (28.07%) 
Protein total increased  1  0/12 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  1/10 (10.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/57 (1.75%) 
Red blood cell count decreased  1  1/12 (8.33%)  0/11 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/57 (1.75%) 
Urine analysis abnormal  1  0/12 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  0/6 (0.00%)  1/57 (1.75%) 
Vanillyl mandelic acid urine increased  1  0/12 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  0/6 (0.00%)  1/57 (1.75%) 
Weight decreased  1  0/12 (0.00%)  1/11 (9.09%)  2/10 (20.00%)  1/10 (10.00%)  0/4 (0.00%)  1/4 (25.00%)  2/6 (33.33%)  7/57 (12.28%) 
White blood cell count decreased  1  3/12 (25.00%)  0/11 (0.00%)  0/10 (0.00%)  5/10 (50.00%)  2/4 (50.00%)  0/4 (0.00%)  3/6 (50.00%)  13/57 (22.81%) 
Metabolism and nutrition disorders                 
Decreased appetite  1  4/12 (33.33%)  4/11 (36.36%)  4/10 (40.00%)  4/10 (40.00%)  1/4 (25.00%)  2/4 (50.00%)  3/6 (50.00%)  22/57 (38.60%) 
Dehydration  1  0/12 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  1/57 (1.75%) 
Hypercalcaemia  1  1/12 (8.33%)  0/11 (0.00%)  1/10 (10.00%)  0/10 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  2/57 (3.51%) 
Hyperglycaemia  1  0/12 (0.00%)  1/11 (9.09%)  1/10 (10.00%)  0/10 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  2/57 (3.51%) 
Hyperkalaemia  1  1/12 (8.33%)  0/11 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  2/6 (33.33%)  3/57 (5.26%) 
Hyperphosphataemia  1  1/12 (8.33%)  0/11 (0.00%)  0/10 (0.00%)  1/10 (10.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  2/57 (3.51%) 
Hypoalbuminaemia  1  2/12 (16.67%)  0/11 (0.00%)  1/10 (10.00%)  2/10 (20.00%)  0/4 (0.00%)  0/4 (0.00%)  2/6 (33.33%)  7/57 (12.28%) 
Hypocalcaemia  1  1/12 (8.33%)  2/11 (18.18%)  1/10 (10.00%)  1/10 (10.00%)  0/4 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  6/57 (10.53%) 
Hypokalaemia  1  1/12 (8.33%)  0/11 (0.00%)  1/10 (10.00%)  0/10 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  2/57 (3.51%) 
Hypomagnesaemia  1  0/12 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  2/10 (20.00%)  0/4 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  3/57 (5.26%) 
Hyponatraemia  1  1/12 (8.33%)  1/11 (9.09%)  1/10 (10.00%)  2/10 (20.00%)  0/4 (0.00%)  1/4 (25.00%)  0/6 (0.00%)  6/57 (10.53%) 
Hypophosphataemia  1  0/12 (0.00%)  0/11 (0.00%)  2/10 (20.00%)  1/10 (10.00%)  0/4 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  4/57 (7.02%) 
Vitamin D deficiency  1  1/12 (8.33%)  0/11 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/57 (1.75%) 
Musculoskeletal and connective tissue disorders                 
Arthralgia  1  1/12 (8.33%)  1/11 (9.09%)  1/10 (10.00%)  1/10 (10.00%)  1/4 (25.00%)  1/4 (25.00%)  0/6 (0.00%)  6/57 (10.53%) 
Back pain  1  2/12 (16.67%)  4/11 (36.36%)  5/10 (50.00%)  2/10 (20.00%)  2/4 (50.00%)  0/4 (0.00%)  1/6 (16.67%)  16/57 (28.07%) 
Bone pain  1  0/12 (0.00%)  0/11 (0.00%)  1/10 (10.00%)  1/10 (10.00%)  1/4 (25.00%)  1/4 (25.00%)  0/6 (0.00%)  4/57 (7.02%) 
Groin pain  1  0/12 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  0/6 (0.00%)  1/57 (1.75%) 
Joint effusion  1  0/12 (0.00%)  0/11 (0.00%)  1/10 (10.00%)  0/10 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/57 (1.75%) 
Joint range of motion decreased  1  0/12 (0.00%)  1/11 (9.09%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/57 (1.75%) 
Muscle spasms  1  0/12 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  2/10 (20.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  2/57 (3.51%) 
Myalgia  1  1/12 (8.33%)  1/11 (9.09%)  1/10 (10.00%)  1/10 (10.00%)  0/4 (0.00%)  1/4 (25.00%)  0/6 (0.00%)  5/57 (8.77%) 
Neck pain  1  1/12 (8.33%)  0/11 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/57 (1.75%) 
Osteopenia  1  1/12 (8.33%)  0/11 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/57 (1.75%) 
Pain in extremity  1  3/12 (25.00%)  2/11 (18.18%)  2/10 (20.00%)  4/10 (40.00%)  1/4 (25.00%)  1/4 (25.00%)  1/6 (16.67%)  14/57 (24.56%) 
Trismus  1  1/12 (8.33%)  0/11 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/57 (1.75%) 
Nervous system disorders                 
Cognitive disorder  1  0/12 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  1/4 (25.00%)  0/6 (0.00%)  1/57 (1.75%) 
Dizziness  1  0/12 (0.00%)  0/11 (0.00%)  2/10 (20.00%)  3/10 (30.00%)  0/4 (0.00%)  1/4 (25.00%)  0/6 (0.00%)  6/57 (10.53%) 
Dysgeusia  1  0/12 (0.00%)  0/11 (0.00%)  2/10 (20.00%)  0/10 (0.00%)  0/4 (0.00%)  1/4 (25.00%)  0/6 (0.00%)  3/57 (5.26%) 
Headache  1  2/12 (16.67%)  3/11 (27.27%)  2/10 (20.00%)  2/10 (20.00%)  1/4 (25.00%)  0/4 (0.00%)  1/6 (16.67%)  11/57 (19.30%) 
Hypersomnia  1  0/12 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  1/57 (1.75%) 
Lethargy  1  0/12 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  1/57 (1.75%) 
Paraesthesia  1  0/12 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  1/10 (10.00%)  0/4 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  2/57 (3.51%) 
Peripheral sensory neuropathy  1  0/12 (0.00%)  0/11 (0.00%)  2/10 (20.00%)  0/10 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  2/57 (3.51%) 
Somnolence  1  0/12 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  1/10 (10.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/57 (1.75%) 
Psychiatric disorders                 
Anxiety  1  0/12 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  2/10 (20.00%)  0/4 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  3/57 (5.26%) 
Depression  1  0/12 (0.00%)  0/11 (0.00%)  3/10 (30.00%)  0/10 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  3/57 (5.26%) 
Insomnia  1  0/12 (0.00%)  2/11 (18.18%)  0/10 (0.00%)  1/10 (10.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  3/57 (5.26%) 
Intentional self-injury  1  0/12 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  1/4 (25.00%)  0/6 (0.00%)  1/57 (1.75%) 
Irritability  1  0/12 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  1/57 (1.75%) 
Renal and urinary disorders                 
Bladder pain  1  0/12 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  0/6 (0.00%)  1/57 (1.75%) 
Chromaturia  1  0/12 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  1/10 (10.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/57 (1.75%) 
Dysuria  1  0/12 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  1/4 (25.00%)  1/4 (25.00%)  0/6 (0.00%)  2/57 (3.51%) 
Haematuria  1  2/12 (16.67%)  1/11 (9.09%)  1/10 (10.00%)  1/10 (10.00%)  1/4 (25.00%)  1/4 (25.00%)  0/6 (0.00%)  7/57 (12.28%) 
Haemoglobinuria  1  0/12 (0.00%)  0/11 (0.00%)  1/10 (10.00%)  0/10 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/57 (1.75%) 
Leukocyturia  1  0/12 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  1/4 (25.00%)  0/6 (0.00%)  1/57 (1.75%) 
Micturition urgency  1  0/12 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  0/6 (0.00%)  1/57 (1.75%) 
Pollakiuria  1  0/12 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  0/6 (0.00%)  1/57 (1.75%) 
Proteinuria  1  4/12 (33.33%)  1/11 (9.09%)  2/10 (20.00%)  3/10 (30.00%)  1/4 (25.00%)  1/4 (25.00%)  1/6 (16.67%)  13/57 (22.81%) 
Reproductive system and breast disorders                 
Amenorrhoea  1  0/12 (0.00%)  1/11 (9.09%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/57 (1.75%) 
Genital pain  1  0/12 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  1/4 (25.00%)  0/6 (0.00%)  1/57 (1.75%) 
Pelvic pain  1  0/12 (0.00%)  0/11 (0.00%)  1/10 (10.00%)  0/10 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/57 (1.75%) 
Vulvovaginal pain  1  0/12 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  1/4 (25.00%)  0/6 (0.00%)  1/57 (1.75%) 
Respiratory, thoracic and mediastinal disorders                 
Atelectasis  1  0/12 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  2/6 (33.33%)  2/57 (3.51%) 
Catarrh  1  0/12 (0.00%)  1/11 (9.09%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/57 (1.75%) 
Cough  1  3/12 (25.00%)  2/11 (18.18%)  3/10 (30.00%)  3/10 (30.00%)  0/4 (0.00%)  1/4 (25.00%)  1/6 (16.67%)  13/57 (22.81%) 
Dyspnoea  1  1/12 (8.33%)  2/11 (18.18%)  1/10 (10.00%)  2/10 (20.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  6/57 (10.53%) 
Epistaxis  1  2/12 (16.67%)  0/11 (0.00%)  1/10 (10.00%)  2/10 (20.00%)  1/4 (25.00%)  1/4 (25.00%)  0/6 (0.00%)  7/57 (12.28%) 
Haemoptysis  1  0/12 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  2/10 (20.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  2/57 (3.51%) 
Hiccups  1  1/12 (8.33%)  0/11 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/57 (1.75%) 
Hypoxia  1  1/12 (8.33%)  0/11 (0.00%)  0/10 (0.00%)  1/10 (10.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  2/57 (3.51%) 
Nasal congestion  1  2/12 (16.67%)  0/11 (0.00%)  0/10 (0.00%)  2/10 (20.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  4/57 (7.02%) 
Oropharyngeal pain  1  3/12 (25.00%)  0/11 (0.00%)  2/10 (20.00%)  2/10 (20.00%)  0/4 (0.00%)  1/4 (25.00%)  0/6 (0.00%)  8/57 (14.04%) 
Pleural effusion  1  0/12 (0.00%)  0/11 (0.00%)  1/10 (10.00%)  1/10 (10.00%)  0/4 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  3/57 (5.26%) 
Pneumothorax  1  0/12 (0.00%)  0/11 (0.00%)  1/10 (10.00%)  0/10 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  2/57 (3.51%) 
Productive cough  1  0/12 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  1/10 (10.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/57 (1.75%) 
Rhinitis allergic  1  0/12 (0.00%)  0/11 (0.00%)  1/10 (10.00%)  1/10 (10.00%)  0/4 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  3/57 (5.26%) 
Rhinorrhoea  1  1/12 (8.33%)  0/11 (0.00%)  1/10 (10.00%)  2/10 (20.00%)  0/4 (0.00%)  1/4 (25.00%)  0/6 (0.00%)  5/57 (8.77%) 
Sinus pain  1  0/12 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  1/4 (25.00%)  0/6 (0.00%)  1/57 (1.75%) 
Sneezing  1  0/12 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  1/4 (25.00%)  0/6 (0.00%)  1/57 (1.75%) 
Skin and subcutaneous tissue disorders                 
Acne  1  0/12 (0.00%)  1/11 (9.09%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/57 (1.75%) 
Alopecia  1  0/12 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  1/4 (25.00%)  1/6 (16.67%)  2/57 (3.51%) 
Dermatitis acneiform  1  0/12 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  1/4 (25.00%)  0/6 (0.00%)  1/57 (1.75%) 
Dermatitis contact  1  0/12 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  1/4 (25.00%)  0/6 (0.00%)  1/57 (1.75%) 
Dermatitis exfoliative generalised  1  1/12 (8.33%)  0/11 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/57 (1.75%) 
Dry skin  1  0/12 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  0/6 (0.00%)  1/57 (1.75%) 
Hair colour changes  1  1/12 (8.33%)  2/11 (18.18%)  3/10 (30.00%)  2/10 (20.00%)  1/4 (25.00%)  3/4 (75.00%)  1/6 (16.67%)  13/57 (22.81%) 
Hyperhidrosis  1  0/12 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  1/10 (10.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/57 (1.75%) 
Macule  1  1/12 (8.33%)  0/11 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/57 (1.75%) 
Nail disorder  1  0/12 (0.00%)  1/11 (9.09%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/57 (1.75%) 
Palmar-plantar erythrodysaesthesia syndrome  1  1/12 (8.33%)  0/11 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/57 (1.75%) 
Pruritus  1  0/12 (0.00%)  2/11 (18.18%)  0/10 (0.00%)  1/10 (10.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  3/57 (5.26%) 
Rash macular  1  0/12 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  1/10 (10.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/57 (1.75%) 
Rash maculo-papular  1  0/12 (0.00%)  0/11 (0.00%)  2/10 (20.00%)  0/10 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  2/57 (3.51%) 
Skin depigmentation  1  0/12 (0.00%)  0/11 (0.00%)  1/10 (10.00%)  0/10 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/57 (1.75%) 
Skin erosion  1  0/12 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  1/4 (25.00%)  0/6 (0.00%)  1/57 (1.75%) 
Skin hypopigmentation  1  0/12 (0.00%)  0/11 (0.00%)  2/10 (20.00%)  0/10 (0.00%)  0/4 (0.00%)  1/4 (25.00%)  0/6 (0.00%)  3/57 (5.26%) 
Skin lesion  1  0/12 (0.00%)  1/11 (9.09%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/57 (1.75%) 
Urticaria  1  1/12 (8.33%)  0/11 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  1/4 (25.00%)  0/6 (0.00%)  2/57 (3.51%) 
Vascular disorders                 
Flushing  1  0/12 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  0/6 (0.00%)  1/57 (1.75%) 
Hot flush  1  0/12 (0.00%)  0/11 (0.00%)  1/10 (10.00%)  0/10 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/57 (1.75%) 
Hypertension  1  1/12 (8.33%)  2/11 (18.18%)  2/10 (20.00%)  4/10 (40.00%)  1/4 (25.00%)  1/4 (25.00%)  2/6 (33.33%)  13/57 (22.81%) 
Hypotension  1  0/12 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  1/10 (10.00%)  0/4 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  2/57 (3.51%) 
1
Term from vocabulary, MedDRA (22.0)
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
Phone: 862-778-8300
EMail: Novartis.email@novartis.com
Layout table for additonal information
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01956669    
Other Study ID Numbers: 116731
2013-003595-12 ( EudraCT Number )
CPZP034X2203 ( Other Identifier: Novartis )
First Submitted: August 1, 2013
First Posted: October 8, 2013
Results First Submitted: May 4, 2020
Results First Posted: August 12, 2020
Last Update Posted: August 12, 2020