Trial Outcomes & Findings for A Study of Xeloda (Capecitabine) Plus Radiation Therapy in Children With Newly Diagnosed Gliomas (NCT NCT00532948)
NCT ID: NCT00532948
Last Updated: 2016-12-07
Results Overview
The MTD was the dose level at which six evaluable patients had been treated and at most one patient experienced a dose limiting toxicity (DLT) and the next highest dose level was too toxic. Dose escalation occurred if 0 out of 3 or at most 1 out of 6 patients experienced DLT while being treated at a dose level; otherwise the dose was declared unsafe and thus above the MTD.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
24 participants
Primary outcome timeframe
Upto 11 weeks.
Results posted on
2016-12-07
Participant Flow
All participants in the study were enrolled at Pediatric Brain Tumor Consortium (PBTC) institutions in the United States of America (USA), from 24 May 2007 through 27 October 2009.
The study consisted of two periods of dosing: A dose-finding treatment period of 11 weeks and a post radiation treatment phase that lasted for 9 weeks.
Participant milestones
| Measure |
Capecitabine 500 mg/m^2
Capecitabine 500 mg/m\^2 was administered twice daily for 14 days, followed by 7 day rest. Treatment was administered for three cycles with radiation therapy period and 3 cycles without radiation therapy.
|
Capecitabine 650 mg/m^2
Capecitabine 650 mg/m\^2 was administered twice daily for 14 days, followed by 7 day rest. Treatment was administered for three cycles with radiation therapy period and 3 cycles without radiation therapy.
|
Capecitabine 850 mg/m^2
Capecitabine 850 mg/m\^2 was administered twice daily for 14 days, followed by 7 day rest. Treatment was administered for three cycles with radiation therapy period and 3 cycles without radiation therapy.
|
|---|---|---|---|
|
Overall Study
STARTED
|
4
|
14
|
6
|
|
Overall Study
COMPLETED
|
0
|
9
|
2
|
|
Overall Study
NOT COMPLETED
|
4
|
5
|
4
|
Reasons for withdrawal
| Measure |
Capecitabine 500 mg/m^2
Capecitabine 500 mg/m\^2 was administered twice daily for 14 days, followed by 7 day rest. Treatment was administered for three cycles with radiation therapy period and 3 cycles without radiation therapy.
|
Capecitabine 650 mg/m^2
Capecitabine 650 mg/m\^2 was administered twice daily for 14 days, followed by 7 day rest. Treatment was administered for three cycles with radiation therapy period and 3 cycles without radiation therapy.
|
Capecitabine 850 mg/m^2
Capecitabine 850 mg/m\^2 was administered twice daily for 14 days, followed by 7 day rest. Treatment was administered for three cycles with radiation therapy period and 3 cycles without radiation therapy.
|
|---|---|---|---|
|
Overall Study
Protocol Violation
|
1
|
0
|
0
|
|
Overall Study
Death
|
3
|
3
|
4
|
|
Overall Study
Violation of selection criteria at entry
|
0
|
1
|
0
|
|
Overall Study
Failure to return
|
0
|
1
|
0
|
Baseline Characteristics
A Study of Xeloda (Capecitabine) Plus Radiation Therapy in Children With Newly Diagnosed Gliomas
Baseline characteristics by cohort
| Measure |
Capecitabine 500 mg/m^2
n=4 Participants
Capecitabine 500 mg/m\^2 was administered twice daily (ideally administered daily in two divided doses approximately 12 hours apart beginning within 24 hours of the start of radiation therapy) for 14 days, followed by 7 day rest. Treatment was administered for three cycles with radiation therapy period and 3 cycles without radiation therapy.
|
Capecitabine 650 mg/m^2
n=14 Participants
Capecitabine 650 mg/m\^2 was administered twice daily (ideally administered daily in two divided doses approximately 12 hours apart beginning within 24 hours of the start of radiation therapy) for 14 days, followed by 7 day rest. Treatment was administered for three cycles with radiation therapy period and 3 cycles without radiation therapy.
|
Capecitabine 850 mg/m^2
n=6 Participants
Capecitabine 850 mg/m\^2 was administered twice daily (ideally administered daily in two divided doses approximately 12 hours apart beginning within 24 hours of the start of radiation therapy) for 14 days, followed by 7 day rest. Treatment was administered for three cycles with radiation therapy period and 3 cycles without radiation therapy.
|
Total
n=24 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
7.5 years
STANDARD_DEVIATION 1.73 • n=5 Participants
|
8.4 years
STANDARD_DEVIATION 2.65 • n=7 Participants
|
13 years
STANDARD_DEVIATION 3.41 • n=5 Participants
|
9.37 years
STANDARD_DEVIATION 3.39 • n=4 Participants
|
|
Gender
Female
|
1 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
15 Participants
n=4 Participants
|
|
Gender
Male
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
9 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Upto 11 weeks.Population: The safety population consisted of all eligible patients who received at least one dose of capecitabine.
The MTD was the dose level at which six evaluable patients had been treated and at most one patient experienced a dose limiting toxicity (DLT) and the next highest dose level was too toxic. Dose escalation occurred if 0 out of 3 or at most 1 out of 6 patients experienced DLT while being treated at a dose level; otherwise the dose was declared unsafe and thus above the MTD.
Outcome measures
| Measure |
Capecitabine (Overall)
n=22 Participants
Capecitabine 500, 650, and 850 mg/m\^2 was administered twice daily for 14 days, followed by 7 day rest. Treatment was administered for three cycles with radiation therapy period and 3 cycles without radiation therapy
|
Capecitabine 650 mg/m^2
Capecitabine 650 mg/m\^2 was administered twice daily for 14 days, followed by 7 day rest. Treatment was administered for three cycles with radiation therapy period and 3 cycles without radiation therapy
|
Capecitabine 850 mg/m^2
Capecitabine 850 mg/m\^2 was administered twice daily for 14 days, followed by 7 day rest. Treatment was administered for three cycles with radiation therapy period and 3 cycles without radiation therapy
|
|---|---|---|---|
|
Maximum Tolerated Dose (MTD) of Capecitabine.
|
650 milligrams
|
—
|
—
|
PRIMARY outcome
Timeframe: Upto 11 weeksPopulation: The safety population consisted of all eligible patients who received at least one dose of capecitabine.
DLT was defined as any of the following events occurring during the 11 week dose-finding period: any event that leads to interruption of planned radiation for 5 consecutive days or 10 days total; Grade 4 neutropenia or thrombocytopenia; Grade 3 thrombocytopenia that required a platelet transfusion on 2 or more occasions; any Grade 3 or 4 non-hematologic toxicity (with the exception of grade 3 nausea or vomiting of less than 5 days duration, Grade 3 transaminases that returned to baseline value within 7 days of study drug interruption and that did not recur upon re-challenge with study drug, and/or Grade 3 fever or infection of \<5 days duration); Grade 2 non-hematologic toxicities that persisted for \>7 days and required treatment interruption, or any other capecitabine-related adverse events that required need for dose reduction or permanent cessation of therapy, interruption of study drug for \>7 days or recurred on re-challenge with capecitabine rapidly disintegrating tablets (RDTs).
Outcome measures
| Measure |
Capecitabine (Overall)
n=4 Participants
Capecitabine 500, 650, and 850 mg/m\^2 was administered twice daily for 14 days, followed by 7 day rest. Treatment was administered for three cycles with radiation therapy period and 3 cycles without radiation therapy
|
Capecitabine 650 mg/m^2
n=12 Participants
Capecitabine 650 mg/m\^2 was administered twice daily for 14 days, followed by 7 day rest. Treatment was administered for three cycles with radiation therapy period and 3 cycles without radiation therapy
|
Capecitabine 850 mg/m^2
n=6 Participants
Capecitabine 850 mg/m\^2 was administered twice daily for 14 days, followed by 7 day rest. Treatment was administered for three cycles with radiation therapy period and 3 cycles without radiation therapy
|
|---|---|---|---|
|
Dose Limiting Toxicities (DLTs)
|
0 Participants
|
3 Participants
|
3 Participants
|
PRIMARY outcome
Timeframe: Up to 06 yearsPopulation: The safety population consisted of all eligible patients who received at least one dose of capecitabine.
An AE is an unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Toxicity was monitored and graded according to the Cancer Therapy Evaluation Program Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. Adverse events that were not included in the CTCAEv3.0 were reported and graded under the other AE within the appropriate category.
Outcome measures
| Measure |
Capecitabine (Overall)
n=4 Participants
Capecitabine 500, 650, and 850 mg/m\^2 was administered twice daily for 14 days, followed by 7 day rest. Treatment was administered for three cycles with radiation therapy period and 3 cycles without radiation therapy
|
Capecitabine 650 mg/m^2
n=12 Participants
Capecitabine 650 mg/m\^2 was administered twice daily for 14 days, followed by 7 day rest. Treatment was administered for three cycles with radiation therapy period and 3 cycles without radiation therapy
|
Capecitabine 850 mg/m^2
n=6 Participants
Capecitabine 850 mg/m\^2 was administered twice daily for 14 days, followed by 7 day rest. Treatment was administered for three cycles with radiation therapy period and 3 cycles without radiation therapy
|
|---|---|---|---|
|
Number of Participants With Adverse Events (AE)
|
3 Participants
|
12 Participants
|
6 Participants
|
PRIMARY outcome
Timeframe: Up to 06 yearsPopulation: The safety population consisted of all eligible patients who received at least one dose of capecitabine. Participants available at a particular time point were included in analysis.
For hematology, the parameters assessed were: Hemoglobin, hematocrit, platelet count, RBC, WBC, lymphocytes, monocytes,granulocytes (blasts), neutrophils(segs, bands),eosinophils and basophils.
Outcome measures
| Measure |
Capecitabine (Overall)
n=4 Participants
Capecitabine 500, 650, and 850 mg/m\^2 was administered twice daily for 14 days, followed by 7 day rest. Treatment was administered for three cycles with radiation therapy period and 3 cycles without radiation therapy
|
Capecitabine 650 mg/m^2
n=12 Participants
Capecitabine 650 mg/m\^2 was administered twice daily for 14 days, followed by 7 day rest. Treatment was administered for three cycles with radiation therapy period and 3 cycles without radiation therapy
|
Capecitabine 850 mg/m^2
n=6 Participants
Capecitabine 850 mg/m\^2 was administered twice daily for 14 days, followed by 7 day rest. Treatment was administered for three cycles with radiation therapy period and 3 cycles without radiation therapy
|
|---|---|---|---|
|
Number of Participants With Baseline Shift From Normal to Low or High in Hematology Parameters
Haematocrit, normal to low, n=3,1,5
|
2 Participants
|
1 Participants
|
4 Participants
|
|
Number of Participants With Baseline Shift From Normal to Low or High in Hematology Parameters
White blood cell, normal to high, n=3,1,5
|
1 Participants
|
1 Participants
|
1 Participants
|
|
Number of Participants With Baseline Shift From Normal to Low or High in Hematology Parameters
Platelets, normal to high, n=4,2,6
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Baseline Shift From Normal to Low or High in Hematology Parameters
Red blood cells, normal to low, n=3,1,3
|
2 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Baseline Shift From Normal to Low or High in Hematology Parameters
Red blood cells, normal to high, n=3,1,3
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Baseline Shift From Normal to Low or High in Hematology Parameters
Neutrophils (segmented), normal to high, n=3,0,5
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Baseline Shift From Normal to Low or High in Hematology Parameters
Basophils (relative), normal to low, n=0,1,2
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Baseline Shift From Normal to Low or High in Hematology Parameters
Lymphocytes (relative), normal to low, n=3,1,5
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Baseline Shift From Normal to Low or High in Hematology Parameters
Monocytes (relative), normal to low, n=3,1,4
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Baseline Shift From Normal to Low or High in Hematology Parameters
Eosinophils (relative), normal to high, n=1,1,3
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Baseline Shift From Normal to Low or High in Hematology Parameters
Haematocrit, normal to high, n=3,1,5
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Baseline Shift From Normal to Low or High in Hematology Parameters
Hemoglobin, normal to low, n=4,2,6
|
0 Participants
|
0 Participants
|
2 Participants
|
|
Number of Participants With Baseline Shift From Normal to Low or High in Hematology Parameters
Hemoglobin, normal to high, n=4,2,6
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Baseline Shift From Normal to Low or High in Hematology Parameters
White blood cell, normal to low, n=3,1,5
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Baseline Shift From Normal to Low or High in Hematology Parameters
Platelets, normal to low, n=4,2,6
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Baseline Shift From Normal to Low or High in Hematology Parameters
Neutrophils (segmented), normal to low , n=3,0,5
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Baseline Shift From Normal to Low or High in Hematology Parameters
Basophils (relative), normal to high, n=0,1,2
|
0 Participants
|
1 Participants
|
2 Participants
|
|
Number of Participants With Baseline Shift From Normal to Low or High in Hematology Parameters
Lymphocytes (relative), normal to high, n=3,1,5
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Baseline Shift From Normal to Low or High in Hematology Parameters
Monocytes (relative), normal to high, n=3,1,4
|
1 Participants
|
0 Participants
|
3 Participants
|
|
Number of Participants With Baseline Shift From Normal to Low or High in Hematology Parameters
Eosinophils (relative), normal to low, n=1,1,3
|
0 Participants
|
1 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Up to 06 yearsPopulation: The safety population consisted of all eligible patients who received at least one dose of capecitabine. Participants available at a particular time point were included in analysis.
For blood chemistry, the parameters assessed were: Sodium, potassium, calcium, magnesium, chloride, bicarbonate, total protein, albumin, alkaline phosphatase, alanine transaminase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), Lactate dehydrogenase (LDH), total bilirubin, direct bilirubin, indirect bilirubin, creatinine (serum creatinine or creatinine clearance), glucose.
Outcome measures
| Measure |
Capecitabine (Overall)
n=4 Participants
Capecitabine 500, 650, and 850 mg/m\^2 was administered twice daily for 14 days, followed by 7 day rest. Treatment was administered for three cycles with radiation therapy period and 3 cycles without radiation therapy
|
Capecitabine 650 mg/m^2
n=12 Participants
Capecitabine 650 mg/m\^2 was administered twice daily for 14 days, followed by 7 day rest. Treatment was administered for three cycles with radiation therapy period and 3 cycles without radiation therapy
|
Capecitabine 850 mg/m^2
n=6 Participants
Capecitabine 850 mg/m\^2 was administered twice daily for 14 days, followed by 7 day rest. Treatment was administered for three cycles with radiation therapy period and 3 cycles without radiation therapy
|
|---|---|---|---|
|
Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters
Lactic dehydrogenase, normal to low, n=0,0,0
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters
Lactic dehydrogenase, normal to high, n=0,0,0
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters
Indirect bilirubin, normal to low, n=1,1,1
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters
Indirect bilirubin, normal to high, n=1,1,1
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters
BUN, normal to low, n=3,1,5
|
0 Participants
|
0 Participants
|
2 Participants
|
|
Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters
BUN, normal to high, n=3,1,5
|
0 Participants
|
1 Participants
|
1 Participants
|
|
Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters
Alkaline phosphatase, normal to low, n=1,1,4
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters
Direct blirubin, normal to low, n=2,1,1
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters
Direct bilirubin, normal to high, n=2,1,1
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters
Total bilirubin, normal to low, n=4,2,6
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters
Total bilirubin, normal to high, n=4,2,6
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters
Fasting glucose, normal to low, n=1,0,4
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters
Fasting glucose, normal to high, n=1,0,4
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters
Serum creatinine, normal to low, n=4,2,6
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters
Serum creatinine, normal to high, n=4,2,6
|
0 Participants
|
0 Participants
|
2 Participants
|
|
Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters
ASAT (SGOT), normal to low, n=1,0,4
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters
ASAT (SGOT), normal to high, n=1,0,4
|
0 Participants
|
0 Participants
|
2 Participants
|
|
Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters
ALAT (SGPT), normal to low, n=4,2,6
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters
ALAT (SGPT), normal to high, n=4,2,6
|
2 Participants
|
2 Participants
|
4 Participants
|
|
Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters
Calcium, normal to low, n=3, 1,5
|
1 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters
Calcium, normal to high, n=3,1,5
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters
Phosphate, normal to low, n=3,1,5
|
1 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters
Phosphate, normal to high, n=3,1,5
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters
Potassium, normal to low, n=3, 1,5
|
2 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters
Sodium, normal to low, n=3,1,5
|
1 Participants
|
1 Participants
|
3 Participants
|
|
Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters
Sodium, normal to high, n=3,1,5
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters
Magnesium, normal to low, n=3,1,5
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters
Magnesium, normal to high, n=3,1,5
|
1 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters
Chloride, normal to high, n=3,1,5
|
0 Participants
|
1 Participants
|
1 Participants
|
|
Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters
Bicarbonate, normal to low, n=3,0,5
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters
Bicarbonate, normal to high, n=3,0,5
|
0 Participants
|
0 Participants
|
3 Participants
|
|
Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters
Alkaline phosphatase, normal to high, n=1,1,4
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters
Protein, normal to low, n=1,0,2
|
1 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters
Protein, normal to high, n=1,0,2
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters
Serum albumin, normal to low, n=3,1,5
|
2 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters
Serum albumin, normal to high, n=3,1,5
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters
Potassium, normal to high, n=3,1,5
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters
Chloride, normal to low, n=3,1,5
|
0 Participants
|
0 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: Day 1 and Day 14Population: The safety population consisted of all eligible patients who received at least one dose of capecitabine. Participants available at a particular time point were included in analysis.
The maximum observed plasma concentration of capecitabine and its metabolites. Participants who consented to participating in the PK studies were randomized to either sampling series A or Series B. The collection time points included 2 different series, Series A (Baseline \[pre-dose\], 10 mins, 30 mins, 1, 2.5, 6, 8 and 10 hours after dosing) and Series B (Baseline \[pre-dose\], 15 minutes, 45 minutes, 1.5, 4, 8 and 10 hours after dosing).
Outcome measures
| Measure |
Capecitabine (Overall)
n=4 Participants
Capecitabine 500, 650, and 850 mg/m\^2 was administered twice daily for 14 days, followed by 7 day rest. Treatment was administered for three cycles with radiation therapy period and 3 cycles without radiation therapy
|
Capecitabine 650 mg/m^2
n=6 Participants
Capecitabine 650 mg/m\^2 was administered twice daily for 14 days, followed by 7 day rest. Treatment was administered for three cycles with radiation therapy period and 3 cycles without radiation therapy
|
Capecitabine 850 mg/m^2
n=5 Participants
Capecitabine 850 mg/m\^2 was administered twice daily for 14 days, followed by 7 day rest. Treatment was administered for three cycles with radiation therapy period and 3 cycles without radiation therapy
|
|---|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax) of Capecitabine and Its Metabolites (5'-Deoxy-5-Fluorocytidine [5'-DFCR], 5'-Deoxy-5-Fluorouridine [5'-DFUR], 5-Fluorouracil [5-FU] and Alpha-fluoro-beta-alanine [FBAL])
Capecitabine, Day 1, n= 2, 4, 3
|
1440 ng/mL
Standard Deviation 750
|
3080 ng/mL
Standard Deviation 1340
|
1890 ng/mL
Standard Deviation 1420
|
|
Maximum Observed Plasma Concentration (Cmax) of Capecitabine and Its Metabolites (5'-Deoxy-5-Fluorocytidine [5'-DFCR], 5'-Deoxy-5-Fluorouridine [5'-DFUR], 5-Fluorouracil [5-FU] and Alpha-fluoro-beta-alanine [FBAL])
Capecitabine, Day 14, n=2,2,2
|
2100 ng/mL
Standard Deviation 1770
|
5440 ng/mL
Standard Deviation 3270
|
3710 ng/mL
Standard Deviation 156
|
|
Maximum Observed Plasma Concentration (Cmax) of Capecitabine and Its Metabolites (5'-Deoxy-5-Fluorocytidine [5'-DFCR], 5'-Deoxy-5-Fluorouridine [5'-DFUR], 5-Fluorouracil [5-FU] and Alpha-fluoro-beta-alanine [FBAL])
5'-DFCR, Day 1, n=2,4,3
|
2050 ng/mL
Standard Deviation 813
|
2190 ng/mL
Standard Deviation 626
|
2180 ng/mL
Standard Deviation 1690
|
|
Maximum Observed Plasma Concentration (Cmax) of Capecitabine and Its Metabolites (5'-Deoxy-5-Fluorocytidine [5'-DFCR], 5'-Deoxy-5-Fluorouridine [5'-DFUR], 5-Fluorouracil [5-FU] and Alpha-fluoro-beta-alanine [FBAL])
5'-DFCR, Day 14, n=2,2,2
|
2980 ng/mL
Standard Deviation 2020
|
3500 ng/mL
Standard Deviation 1470
|
3200 ng/mL
Standard Deviation 233
|
|
Maximum Observed Plasma Concentration (Cmax) of Capecitabine and Its Metabolites (5'-Deoxy-5-Fluorocytidine [5'-DFCR], 5'-Deoxy-5-Fluorouridine [5'-DFUR], 5-Fluorouracil [5-FU] and Alpha-fluoro-beta-alanine [FBAL])
5'-DFUR, Day 1, n=2,4,3
|
1910 ng/mL
Standard Deviation 834
|
2640 ng/mL
Standard Deviation 1700
|
3770 ng/mL
Standard Deviation 3300
|
|
Maximum Observed Plasma Concentration (Cmax) of Capecitabine and Its Metabolites (5'-Deoxy-5-Fluorocytidine [5'-DFCR], 5'-Deoxy-5-Fluorouridine [5'-DFUR], 5-Fluorouracil [5-FU] and Alpha-fluoro-beta-alanine [FBAL])
5'-DFUR, Day 14, n=2,2,2
|
3300 ng/mL
Standard Deviation 2800
|
3120 ng/mL
Standard Deviation 445
|
5020 ng/mL
Standard Deviation 1220
|
|
Maximum Observed Plasma Concentration (Cmax) of Capecitabine and Its Metabolites (5'-Deoxy-5-Fluorocytidine [5'-DFCR], 5'-Deoxy-5-Fluorouridine [5'-DFUR], 5-Fluorouracil [5-FU] and Alpha-fluoro-beta-alanine [FBAL])
FBAL, Day 1, n=2,4,3
|
1350 ng/mL
Standard Deviation 134
|
1740 ng/mL
Standard Deviation 365
|
2050 ng/mL
Standard Deviation 1640
|
|
Maximum Observed Plasma Concentration (Cmax) of Capecitabine and Its Metabolites (5'-Deoxy-5-Fluorocytidine [5'-DFCR], 5'-Deoxy-5-Fluorouridine [5'-DFUR], 5-Fluorouracil [5-FU] and Alpha-fluoro-beta-alanine [FBAL])
FBAL, Day 14, n=2,2,2
|
1770 ng/mL
Standard Deviation 410
|
2430 ng/mL
Standard Deviation 84.9
|
2140 ng/mL
Standard Deviation 304
|
SECONDARY outcome
Timeframe: Day 1 and Day 14Population: The safety population consisted of all eligible patients who received at least one dose of capecitabine. Participants available at a particular time point were included in analysis.
Tmax is the corresponding time at which Cmax occurs of capecitabine and its metabolites.Participants who consented to participating in the PK studies were randomized to either sampling series A or Series B. The collection time points included 2 different series, Series A (Baseline \[pre-dose\], 10 mins, 30 mins, 1, 2.5, 6, 8 and 10 hours after dosing) and Series B (Baseline \[pre-dose\], 15 minutes, 45 minutes, 1.5, 4, 8 and 10 hours after dosing).
Outcome measures
| Measure |
Capecitabine (Overall)
n=4 Participants
Capecitabine 500, 650, and 850 mg/m\^2 was administered twice daily for 14 days, followed by 7 day rest. Treatment was administered for three cycles with radiation therapy period and 3 cycles without radiation therapy
|
Capecitabine 650 mg/m^2
n=6 Participants
Capecitabine 650 mg/m\^2 was administered twice daily for 14 days, followed by 7 day rest. Treatment was administered for three cycles with radiation therapy period and 3 cycles without radiation therapy
|
Capecitabine 850 mg/m^2
n=5 Participants
Capecitabine 850 mg/m\^2 was administered twice daily for 14 days, followed by 7 day rest. Treatment was administered for three cycles with radiation therapy period and 3 cycles without radiation therapy
|
|---|---|---|---|
|
Time to Maximum Plasma Concentration (Tmax) of Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR, 5-FU and FBAL)
5'-DFCR, Day 1, n=2,4,3
|
1.0 Hour
Interval 1.0 to 1.0
|
0.75 Hour
Interval 0.5 to 2.5
|
1.55 Hour
Interval 0.85 to 10.0
|
|
Time to Maximum Plasma Concentration (Tmax) of Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR, 5-FU and FBAL)
5'-DFCR, Day 14, n=2,2,2
|
1.49 Hour
Interval 0.5 to 2.48
|
1.18 Hour
Interval 0.5 to 1.53
|
0.61 Hour
Interval 0.5 to 1.53
|
|
Time to Maximum Plasma Concentration (Tmax) of Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR, 5-FU and FBAL)
Capecitabine, Day 1, n= 2, 4, 3
|
0.58 Hour
Interval 0.17 to 1.0
|
0.63 Hour
Interval 0.25 to 1.0
|
0.85 Hour
Interval 0.83 to 10.0
|
|
Time to Maximum Plasma Concentration (Tmax) of Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR, 5-FU and FBAL)
Capecitabine, Day 14, n=2,2,2
|
1.33 Hour
Interval 0.17 to 2.48
|
0.82 Hour
Interval 0.8 to 0.83
|
0.61 Hour
Interval 0.5 to 0.72
|
|
Time to Maximum Plasma Concentration (Tmax) of Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR, 5-FU and FBAL)
5'-DFUR, Day 1, n=2,4,3
|
1 Hour
Interval 1.0 to 1.0
|
0.9 Hour
Interval 0.7 to 2.5
|
1.5 Hour
Interval 0.75 to 10.0
|
|
Time to Maximum Plasma Concentration (Tmax) of Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR, 5-FU and FBAL)
5'-DFUR, Day 14, n=2,2,2
|
1.5 Hour
Interval 0.5 to 2.5
|
0.82 Hour
Interval 0.8 to 0.83
|
0.61 Hour
Interval 0.5 to 0.72
|
|
Time to Maximum Plasma Concentration (Tmax) of Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR, 5-FU and FBAL)
5-FU, Day 1, n=2,4,3
|
1 Hour
Interval 1.0 to 1.0
|
0.75 Hour
Interval 0.5 to 2.5
|
1.5 Hour
Interval 0.75 to 10.0
|
|
Time to Maximum Plasma Concentration (Tmax) of Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR, 5-FU and FBAL)
5-FU, Day 14, n=2,2,2
|
1.5 Hour
Interval 0.5 to 2.5
|
0.83 Hour
Interval 0.8 to 0.83
|
1 Hour
Interval 0.5 to 1.5
|
|
Time to Maximum Plasma Concentration (Tmax) of Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR, 5-FU and FBAL)
FBAL, Day 1, n=2,4,3
|
2.53 Hour
Interval 2.5 to 2.53
|
1.5 Hour
Interval 1.5 to 2.5
|
1.55 Hour
Interval 1.42 to 10.0
|
|
Time to Maximum Plasma Concentration (Tmax) of Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR, 5-FU and FBAL)
FBAL, Day 14, n=2,2,2
|
1.74 Hour
Interval 1.0 to 2.5
|
2.2 Hour
Interval 1.5 to 2.8
|
2.03 Hour
Interval 1.57 to 2.5
|
SECONDARY outcome
Timeframe: Day 1 and Day 14Population: The safety population consisted of all eligible patients who received at least one dose of capecitabine. Participants available at a particular time point were included in analysis.
AUC last concentration of capecitabine and its metabolites. Participants who consented to participating in the PK studies were randomized to either sampling series A or Series B. The collection time points included 2 different series, Series A (Baseline \[pre-dose\], 10 mins, 30 mins, 1, 2.5, 6, 8 and 10 hours after dosing) and Series B (Baseline \[pre-dose\], 15 minutes, 45 minutes, 1.5, 4, 8 and 10 hours after dosing).
Outcome measures
| Measure |
Capecitabine (Overall)
n=4 Participants
Capecitabine 500, 650, and 850 mg/m\^2 was administered twice daily for 14 days, followed by 7 day rest. Treatment was administered for three cycles with radiation therapy period and 3 cycles without radiation therapy
|
Capecitabine 650 mg/m^2
n=6 Participants
Capecitabine 650 mg/m\^2 was administered twice daily for 14 days, followed by 7 day rest. Treatment was administered for three cycles with radiation therapy period and 3 cycles without radiation therapy
|
Capecitabine 850 mg/m^2
n=5 Participants
Capecitabine 850 mg/m\^2 was administered twice daily for 14 days, followed by 7 day rest. Treatment was administered for three cycles with radiation therapy period and 3 cycles without radiation therapy
|
|---|---|---|---|
|
The Area Under the Plasma Concentration-time Curve From Time of Dosing to the Last Measurable Concentration (AUClast) of Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR, 5-FU and FBAL)
Capecitabine, Day 1, n= 2, 4, 3
|
3370 h*ng/mL
Standard Deviation 607
|
5160 h*ng/mL
Standard Deviation 3700
|
3470 h*ng/mL
Standard Deviation 1170
|
|
The Area Under the Plasma Concentration-time Curve From Time of Dosing to the Last Measurable Concentration (AUClast) of Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR, 5-FU and FBAL)
Capecitabine, Day 14, n=2,2,2
|
2890 h*ng/mL
Standard Deviation 655
|
9660 h*ng/mL
Standard Deviation 3340
|
5670 h*ng/mL
Standard Deviation 971
|
|
The Area Under the Plasma Concentration-time Curve From Time of Dosing to the Last Measurable Concentration (AUClast) of Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR, 5-FU and FBAL)
5'-DFCR, Day 1, n=2,4,3
|
5250 h*ng/mL
Standard Deviation 755
|
5140 h*ng/mL
Standard Deviation 3440
|
4180 h*ng/mL
Standard Deviation 2380
|
|
The Area Under the Plasma Concentration-time Curve From Time of Dosing to the Last Measurable Concentration (AUClast) of Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR, 5-FU and FBAL)
5'-DFCR, Day 14, n=2,2,2
|
4300 h*ng/mL
Standard Deviation 27.2
|
9250 h*ng/mL
Standard Deviation 1400
|
6520 h*ng/mL
Standard Deviation 452
|
|
The Area Under the Plasma Concentration-time Curve From Time of Dosing to the Last Measurable Concentration (AUClast) of Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR, 5-FU and FBAL)
5'-DFUR, Day 1, n=2,4,3
|
4790 h*ng/mL
Standard Deviation 784
|
4300 h*ng/mL
Standard Deviation 1600
|
6650 h*ng/mL
Standard Deviation 3740
|
|
The Area Under the Plasma Concentration-time Curve From Time of Dosing to the Last Measurable Concentration (AUClast) of Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR, 5-FU and FBAL)
5'-DFUR, Day 14, n=2,2,2
|
4240 h*ng/mL
Standard Deviation 929
|
8010 h*ng/mL
Standard Deviation 1890
|
10500 h*ng/mL
Standard Deviation 445
|
|
The Area Under the Plasma Concentration-time Curve From Time of Dosing to the Last Measurable Concentration (AUClast) of Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR, 5-FU and FBAL)
5-FU Day 1, n=2,4,3
|
81.6 h*ng/mL
Standard Deviation 29.7
|
114 h*ng/mL
Standard Deviation 40.9
|
271 h*ng/mL
Standard Deviation 205
|
|
The Area Under the Plasma Concentration-time Curve From Time of Dosing to the Last Measurable Concentration (AUClast) of Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR, 5-FU and FBAL)
5-FU Day 14, n=2,2,2
|
181 h*ng/mL
Standard Deviation 84.7
|
253 h*ng/mL
Standard Deviation 16.3
|
499 h*ng/mL
Standard Deviation 78.8
|
|
The Area Under the Plasma Concentration-time Curve From Time of Dosing to the Last Measurable Concentration (AUClast) of Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR, 5-FU and FBAL)
FBAL, Day 1, n=2,4,3
|
5990 h*ng/mL
Standard Deviation 951
|
8110 h*ng/mL
Standard Deviation 1640
|
7010 h*ng/mL
Standard Deviation 4490
|
|
The Area Under the Plasma Concentration-time Curve From Time of Dosing to the Last Measurable Concentration (AUClast) of Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR, 5-FU and FBAL)
FBAL, Day 14, n=2,2,2
|
5720 h*ng/mL
Standard Deviation 690
|
10700 h*ng/mL
Standard Deviation 574
|
10400 h*ng/mL
Standard Deviation 1760
|
SECONDARY outcome
Timeframe: Up to 6 yearsPopulation: Efficacy data of the present study (NO18517 - NCT00532948) were pre-specified to be combined with efficacy data of the Phase 2 portion of this Study, NO21125 (NCT01118377) for analysis. Results are currently posted in the record of Study NO21125.
Tumor response refers to the best response prior to failure (disease progression, death or second malignancy).
Outcome measures
Outcome data not reported
Adverse Events
Capecitabine 500 mg/m^2
Serious events: 2 serious events
Other events: 3 other events
Deaths: 0 deaths
Capecitabine 650 mg/m^2
Serious events: 1 serious events
Other events: 12 other events
Deaths: 0 deaths
Capecitabine 850 mg/m^2
Serious events: 3 serious events
Other events: 6 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Capecitabine 500 mg/m^2
n=4 participants at risk
Capecitabine 500 mg/m\^2 was administered twice daily for 14 days, followed by 7 day rest. Treatment was administered for three cycles with radiation therapy period and 3 cycles without radiation therapy
|
Capecitabine 650 mg/m^2
n=12 participants at risk
Capecitabine 650 mg/m\^2 was administered twice daily for 14 days, followed by 7 day rest. Treatment was administered for three cycles with radiation therapy period and 3 cycles without radiation therapy
|
Capecitabine 850 mg/m^2
n=6 participants at risk
Capecitabine 850 mg/m\^2 was administered twice daily for 14 days, followed by 7 day rest. Treatment was administered for three cycles with radiation therapy period and 3 cycles without radiation therapy
|
|---|---|---|---|
|
Nervous system disorders
Convulsion
|
0.00%
0/4 • Up to 6 years
|
0.00%
0/12 • Up to 6 years
|
16.7%
1/6 • Up to 6 years
|
|
Nervous system disorders
Hydrocephalus
|
25.0%
1/4 • Up to 6 years
|
0.00%
0/12 • Up to 6 years
|
0.00%
0/6 • Up to 6 years
|
|
Skin and subcutaneous tissue disorders
Dermatitis Exfoliative
|
0.00%
0/4 • Up to 6 years
|
8.3%
1/12 • Up to 6 years
|
0.00%
0/6 • Up to 6 years
|
|
Skin and subcutaneous tissue disorders
Skin Exfoliation
|
0.00%
0/4 • Up to 6 years
|
0.00%
0/12 • Up to 6 years
|
16.7%
1/6 • Up to 6 years
|
|
Blood and lymphatic system disorders
Leukopenia
|
25.0%
1/4 • Up to 6 years
|
0.00%
0/12 • Up to 6 years
|
0.00%
0/6 • Up to 6 years
|
|
General disorders
Pain
|
0.00%
0/4 • Up to 6 years
|
8.3%
1/12 • Up to 6 years
|
0.00%
0/6 • Up to 6 years
|
|
Infections and infestations
Abdominal Infection
|
0.00%
0/4 • Up to 6 years
|
0.00%
0/12 • Up to 6 years
|
16.7%
1/6 • Up to 6 years
|
|
Investigations
Blood Creatinine Increased
|
0.00%
0/4 • Up to 6 years
|
0.00%
0/12 • Up to 6 years
|
16.7%
1/6 • Up to 6 years
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.00%
0/4 • Up to 6 years
|
8.3%
1/12 • Up to 6 years
|
0.00%
0/6 • Up to 6 years
|
Other adverse events
| Measure |
Capecitabine 500 mg/m^2
n=4 participants at risk
Capecitabine 500 mg/m\^2 was administered twice daily for 14 days, followed by 7 day rest. Treatment was administered for three cycles with radiation therapy period and 3 cycles without radiation therapy
|
Capecitabine 650 mg/m^2
n=12 participants at risk
Capecitabine 650 mg/m\^2 was administered twice daily for 14 days, followed by 7 day rest. Treatment was administered for three cycles with radiation therapy period and 3 cycles without radiation therapy
|
Capecitabine 850 mg/m^2
n=6 participants at risk
Capecitabine 850 mg/m\^2 was administered twice daily for 14 days, followed by 7 day rest. Treatment was administered for three cycles with radiation therapy period and 3 cycles without radiation therapy
|
|---|---|---|---|
|
Investigations
Alanine aminotransferase increased
|
25.0%
1/4 • Up to 6 years
|
75.0%
9/12 • Up to 6 years
|
50.0%
3/6 • Up to 6 years
|
|
Investigations
Haemoglobin
|
25.0%
1/4 • Up to 6 years
|
33.3%
4/12 • Up to 6 years
|
33.3%
2/6 • Up to 6 years
|
|
Investigations
Neutrophil count
|
50.0%
2/4 • Up to 6 years
|
33.3%
4/12 • Up to 6 years
|
16.7%
1/6 • Up to 6 years
|
|
Investigations
Platelet count decreased
|
50.0%
2/4 • Up to 6 years
|
41.7%
5/12 • Up to 6 years
|
0.00%
0/6 • Up to 6 years
|
|
Investigations
Weight increased
|
25.0%
1/4 • Up to 6 years
|
25.0%
3/12 • Up to 6 years
|
33.3%
2/6 • Up to 6 years
|
|
Investigations
Aspartate aminotransferase increased
|
0.00%
0/4 • Up to 6 years
|
16.7%
2/12 • Up to 6 years
|
16.7%
1/6 • Up to 6 years
|
|
Investigations
Blood bicarbonate decreased
|
25.0%
1/4 • Up to 6 years
|
8.3%
1/12 • Up to 6 years
|
16.7%
1/6 • Up to 6 years
|
|
Investigations
Blood alkaline phosphatase increased
|
0.00%
0/4 • Up to 6 years
|
8.3%
1/12 • Up to 6 years
|
16.7%
1/6 • Up to 6 years
|
|
Investigations
Gamma-glutamyltransferase increased
|
0.00%
0/4 • Up to 6 years
|
8.3%
1/12 • Up to 6 years
|
16.7%
1/6 • Up to 6 years
|
|
Investigations
Blood creatinine increased
|
0.00%
0/4 • Up to 6 years
|
0.00%
0/12 • Up to 6 years
|
16.7%
1/6 • Up to 6 years
|
|
Investigations
Weight Decreased
|
0.00%
0/4 • Up to 6 years
|
0.00%
0/12 • Up to 6 years
|
16.7%
1/6 • Up to 6 years
|
|
Blood and lymphatic system disorders
Lymphopenia
|
75.0%
3/4 • Up to 6 years
|
83.3%
10/12 • Up to 6 years
|
50.0%
3/6 • Up to 6 years
|
|
Blood and lymphatic system disorders
Leukopenia
|
75.0%
3/4 • Up to 6 years
|
83.3%
10/12 • Up to 6 years
|
33.3%
2/6 • Up to 6 years
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
50.0%
2/4 • Up to 6 years
|
25.0%
3/12 • Up to 6 years
|
33.3%
2/6 • Up to 6 years
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
25.0%
1/4 • Up to 6 years
|
25.0%
3/12 • Up to 6 years
|
33.3%
2/6 • Up to 6 years
|
|
Metabolism and nutrition disorders
Hypoalbuminaemia
|
50.0%
2/4 • Up to 6 years
|
25.0%
3/12 • Up to 6 years
|
16.7%
1/6 • Up to 6 years
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
25.0%
1/4 • Up to 6 years
|
33.3%
4/12 • Up to 6 years
|
16.7%
1/6 • Up to 6 years
|
|
Metabolism and nutrition disorders
Decreased appetite
|
50.0%
2/4 • Up to 6 years
|
16.7%
2/12 • Up to 6 years
|
16.7%
1/6 • Up to 6 years
|
|
Metabolism and nutrition disorders
Hypercalcaemia
|
25.0%
1/4 • Up to 6 years
|
25.0%
3/12 • Up to 6 years
|
16.7%
1/6 • Up to 6 years
|
|
Metabolism and nutrition disorders
Hypermagnesaemia
|
25.0%
1/4 • Up to 6 years
|
33.3%
4/12 • Up to 6 years
|
0.00%
0/6 • Up to 6 years
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.00%
0/4 • Up to 6 years
|
33.3%
4/12 • Up to 6 years
|
16.7%
1/6 • Up to 6 years
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
50.0%
2/4 • Up to 6 years
|
16.7%
2/12 • Up to 6 years
|
16.7%
1/6 • Up to 6 years
|
|
Metabolism and nutrition disorders
Hypernatraemia
|
25.0%
1/4 • Up to 6 years
|
8.3%
1/12 • Up to 6 years
|
0.00%
0/6 • Up to 6 years
|
|
Metabolism and nutrition disorders
Dehydration
|
25.0%
1/4 • Up to 6 years
|
0.00%
0/12 • Up to 6 years
|
0.00%
0/6 • Up to 6 years
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
25.0%
1/4 • Up to 6 years
|
0.00%
0/12 • Up to 6 years
|
0.00%
0/6 • Up to 6 years
|
|
Gastrointestinal disorders
Vomiting
|
50.0%
2/4 • Up to 6 years
|
75.0%
9/12 • Up to 6 years
|
33.3%
2/6 • Up to 6 years
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/4 • Up to 6 years
|
33.3%
4/12 • Up to 6 years
|
66.7%
4/6 • Up to 6 years
|
|
Gastrointestinal disorders
Nausea
|
25.0%
1/4 • Up to 6 years
|
16.7%
2/12 • Up to 6 years
|
66.7%
4/6 • Up to 6 years
|
|
Gastrointestinal disorders
Constipation
|
25.0%
1/4 • Up to 6 years
|
25.0%
3/12 • Up to 6 years
|
33.3%
2/6 • Up to 6 years
|
|
Gastrointestinal disorders
Diarrhoea
|
50.0%
2/4 • Up to 6 years
|
25.0%
3/12 • Up to 6 years
|
16.7%
1/6 • Up to 6 years
|
|
Gastrointestinal disorders
Abdominal discomfort
|
0.00%
0/4 • Up to 6 years
|
0.00%
0/12 • Up to 6 years
|
16.7%
1/6 • Up to 6 years
|
|
Skin and subcutaneous tissue disorders
Skin exfoliation
|
25.0%
1/4 • Up to 6 years
|
66.7%
8/12 • Up to 6 years
|
66.7%
4/6 • Up to 6 years
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
25.0%
1/4 • Up to 6 years
|
33.3%
4/12 • Up to 6 years
|
16.7%
1/6 • Up to 6 years
|
|
Skin and subcutaneous tissue disorders
Skin hyperpigmentation
|
25.0%
1/4 • Up to 6 years
|
16.7%
2/12 • Up to 6 years
|
50.0%
3/6 • Up to 6 years
|
|
Skin and subcutaneous tissue disorders
Dermatitis exfoliative
|
0.00%
0/4 • Up to 6 years
|
33.3%
4/12 • Up to 6 years
|
16.7%
1/6 • Up to 6 years
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
0.00%
0/4 • Up to 6 years
|
25.0%
3/12 • Up to 6 years
|
0.00%
0/6 • Up to 6 years
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/4 • Up to 6 years
|
16.7%
2/12 • Up to 6 years
|
16.7%
1/6 • Up to 6 years
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
25.0%
1/4 • Up to 6 years
|
0.00%
0/12 • Up to 6 years
|
16.7%
1/6 • Up to 6 years
|
|
Skin and subcutaneous tissue disorders
Acne
|
0.00%
0/4 • Up to 6 years
|
0.00%
0/12 • Up to 6 years
|
16.7%
1/6 • Up to 6 years
|
|
Nervous system disorders
Headache
|
50.0%
2/4 • Up to 6 years
|
33.3%
4/12 • Up to 6 years
|
33.3%
2/6 • Up to 6 years
|
|
Nervous system disorders
Convulsion
|
25.0%
1/4 • Up to 6 years
|
8.3%
1/12 • Up to 6 years
|
16.7%
1/6 • Up to 6 years
|
|
Nervous system disorders
Dizziness
|
25.0%
1/4 • Up to 6 years
|
16.7%
2/12 • Up to 6 years
|
0.00%
0/6 • Up to 6 years
|
|
Nervous system disorders
Facial nerve disorder
|
25.0%
1/4 • Up to 6 years
|
16.7%
2/12 • Up to 6 years
|
0.00%
0/6 • Up to 6 years
|
|
Nervous system disorders
VIth nerve disorder
|
25.0%
1/4 • Up to 6 years
|
16.7%
2/12 • Up to 6 years
|
0.00%
0/6 • Up to 6 years
|
|
Nervous system disorders
Ataxia
|
25.0%
1/4 • Up to 6 years
|
8.3%
1/12 • Up to 6 years
|
0.00%
0/6 • Up to 6 years
|
|
Nervous system disorders
Glossopharyngeal nerve disorder
|
25.0%
1/4 • Up to 6 years
|
0.00%
0/12 • Up to 6 years
|
0.00%
0/6 • Up to 6 years
|
|
Nervous system disorders
Nystagmus
|
25.0%
1/4 • Up to 6 years
|
0.00%
0/12 • Up to 6 years
|
0.00%
0/6 • Up to 6 years
|
|
Nervous system disorders
Peripheral motor neuropathy
|
25.0%
1/4 • Up to 6 years
|
0.00%
0/12 • Up to 6 years
|
0.00%
0/6 • Up to 6 years
|
|
Nervous system disorders
Tremor
|
25.0%
1/4 • Up to 6 years
|
0.00%
0/12 • Up to 6 years
|
0.00%
0/6 • Up to 6 years
|
|
Infections and infestations
Gingival infection
|
0.00%
0/4 • Up to 6 years
|
0.00%
0/12 • Up to 6 years
|
33.3%
2/6 • Up to 6 years
|
|
Infections and infestations
Nasopharyngitis
|
25.0%
1/4 • Up to 6 years
|
8.3%
1/12 • Up to 6 years
|
0.00%
0/6 • Up to 6 years
|
|
Infections and infestations
Otitis media
|
25.0%
1/4 • Up to 6 years
|
8.3%
1/12 • Up to 6 years
|
0.00%
0/6 • Up to 6 years
|
|
Infections and infestations
Respiratory tract infection
|
25.0%
1/4 • Up to 6 years
|
0.00%
0/12 • Up to 6 years
|
16.7%
1/6 • Up to 6 years
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
25.0%
1/4 • Up to 6 years
|
16.7%
2/12 • Up to 6 years
|
0.00%
0/6 • Up to 6 years
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
0.00%
0/4 • Up to 6 years
|
25.0%
3/12 • Up to 6 years
|
0.00%
0/6 • Up to 6 years
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
25.0%
1/4 • Up to 6 years
|
0.00%
0/12 • Up to 6 years
|
16.7%
1/6 • Up to 6 years
|
|
Injury, poisoning and procedural complications
Radiation mucositis
|
25.0%
1/4 • Up to 6 years
|
8.3%
1/12 • Up to 6 years
|
16.7%
1/6 • Up to 6 years
|
|
Injury, poisoning and procedural complications
Thermal burn
|
25.0%
1/4 • Up to 6 years
|
0.00%
0/12 • Up to 6 years
|
16.7%
1/6 • Up to 6 years
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
25.0%
1/4 • Up to 6 years
|
0.00%
0/12 • Up to 6 years
|
16.7%
1/6 • Up to 6 years
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
25.0%
1/4 • Up to 6 years
|
0.00%
0/12 • Up to 6 years
|
0.00%
0/6 • Up to 6 years
|
|
Respiratory, thoracic and mediastinal disorders
Rhinitis allergic
|
0.00%
0/4 • Up to 6 years
|
0.00%
0/12 • Up to 6 years
|
16.7%
1/6 • Up to 6 years
|
|
Endocrine disorders
Cushingoid
|
0.00%
0/4 • Up to 6 years
|
16.7%
2/12 • Up to 6 years
|
16.7%
1/6 • Up to 6 years
|
|
Cardiac disorders
Hypertension
|
25.0%
1/4 • Up to 6 years
|
16.7%
2/12 • Up to 6 years
|
0.00%
0/6 • Up to 6 years
|
|
Eye disorders
Diplopia
|
50.0%
2/4 • Up to 6 years
|
0.00%
0/12 • Up to 6 years
|
0.00%
0/6 • Up to 6 years
|
|
Eye disorders
Extraocular muscle disorder
|
25.0%
1/4 • Up to 6 years
|
0.00%
0/12 • Up to 6 years
|
0.00%
0/6 • Up to 6 years
|
|
Eye disorders
Vision blurred
|
25.0%
1/4 • Up to 6 years
|
0.00%
0/12 • Up to 6 years
|
0.00%
0/6 • Up to 6 years
|
|
Psychiatric disorders
Confusional state
|
0.00%
0/4 • Up to 6 years
|
0.00%
0/12 • Up to 6 years
|
16.7%
1/6 • Up to 6 years
|
|
Psychiatric disorders
Euphoric mood
|
0.00%
0/4 • Up to 6 years
|
0.00%
0/12 • Up to 6 years
|
16.7%
1/6 • Up to 6 years
|
|
Psychiatric disorders
Psychotic Disorder
|
0.00%
0/4 • Up to 6 years
|
0.00%
0/12 • Up to 6 years
|
16.7%
1/6 • Up to 6 years
|
|
Surgical and medical procedures
Oculomotor nerve operation
|
25.0%
1/4 • Up to 6 years
|
0.00%
0/12 • Up to 6 years
|
0.00%
0/6 • Up to 6 years
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
- Publication restrictions are in place
Restriction type: OTHER