Trial Outcomes & Findings for A Study of Xeloda (Capecitabine) in Combination With Oxaliplatin in Patients With Metastatic Colorectal Cancer. (NCT NCT00353262)
NCT ID: NCT00353262
Last Updated: 2016-03-04
Results Overview
AUC0-infinity represents the area under the concentration-time curve of the analyte (5'-DFUR) in plasma over the time interval from 0 extrapolated to infinity. The analyte 5'-DFUR, the direct precursor of 5-fluorouracil (5-FU), is considered to be the most important metabolite of capecitabine in plasma. The unit of measure was nanograms per millilitre per hour (ng/mL \* hr).
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
36 participants
Primary outcome timeframe
Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, and 12 hours post the dose.
Results posted on
2016-03-04
Participant Flow
A total of 36 participants were enrolled in this study at three sites in Canada between 8 August 2005 and 24 April 2008.
Participant milestones
| Measure |
Capecitabine+ Oxaliplatin+ Bevacizumab
In Cycle 1, participants received a single oral dose of capecitabine 1000 milligrams per meter square (mg/m\^2 on Day 1 followed by 2-hour intravenous (IV) infusion of oxaliplatin 130 mg/m\^2 on Day 2 followed by oral dosing of capecitabine 1000 mg/m\^2 twice-daily (BID) from Day 5 to Day 14 . In Cycle 2, participants received IV infusion of oxaliplatin 130 mg//m\^2 over 2 hours on Day 1 along with capecitabine 1000 mg/m\^2 orally BID until Day 14. In Cycle 3, participants received IV infusion of bevacizumab 7.5 mg/kg over 90 minutes on Day 1 at the same time as oxaliplatin 130 mg//m\^2 was administered as an IV infusion over 2 hours (Day 1 every 3 weeks) along with capecitabine1000 mg//m\^2 orally BID until Day 14. Treatment with the Cycle 3 dosing regimen continued for a further 13 cycles (i.e. Cycle 16) or until progressive disease or unacceptable toxicity or until the participant withdrew consent
|
|---|---|
|
Overall Study
STARTED
|
36
|
|
Overall Study
COMPLETED
|
7
|
|
Overall Study
NOT COMPLETED
|
29
|
Reasons for withdrawal
| Measure |
Capecitabine+ Oxaliplatin+ Bevacizumab
In Cycle 1, participants received a single oral dose of capecitabine 1000 milligrams per meter square (mg/m\^2 on Day 1 followed by 2-hour intravenous (IV) infusion of oxaliplatin 130 mg/m\^2 on Day 2 followed by oral dosing of capecitabine 1000 mg/m\^2 twice-daily (BID) from Day 5 to Day 14 . In Cycle 2, participants received IV infusion of oxaliplatin 130 mg//m\^2 over 2 hours on Day 1 along with capecitabine 1000 mg/m\^2 orally BID until Day 14. In Cycle 3, participants received IV infusion of bevacizumab 7.5 mg/kg over 90 minutes on Day 1 at the same time as oxaliplatin 130 mg//m\^2 was administered as an IV infusion over 2 hours (Day 1 every 3 weeks) along with capecitabine1000 mg//m\^2 orally BID until Day 14. Treatment with the Cycle 3 dosing regimen continued for a further 13 cycles (i.e. Cycle 16) or until progressive disease or unacceptable toxicity or until the participant withdrew consent
|
|---|---|
|
Overall Study
Adverse Event
|
8
|
|
Overall Study
Withdrawal by Subject
|
2
|
|
Overall Study
Insufficient Therapeutic Response
|
13
|
|
Overall Study
Progression
|
1
|
|
Overall Study
Surgery
|
4
|
|
Overall Study
Break from Chemotherapy
|
1
|
Baseline Characteristics
A Study of Xeloda (Capecitabine) in Combination With Oxaliplatin in Patients With Metastatic Colorectal Cancer.
Baseline characteristics by cohort
| Measure |
Capecitabine+ Oxaliplatin+ Bevacizumab
n=36 Participants
In Cycle 1, participants received a single oral dose of capecitabine 1000 milligrams per meter square (mg/m\^2 on Day 1 followed by 2-hour intravenous (IV) infusion of oxaliplatin 130 mg/m\^2 on Day 2 followed by oral dosing of capecitabine 1000 mg/m\^2 twice-daily (BID) from Day 5 to Day 14 . In Cycle 2, participants received IV infusion of oxaliplatin 130 mg//m\^2 over 2 hours on Day 1 along with capecitabine 1000 mg/m\^2 orally BID until Day 14. In Cycle 3, participants received IV infusion of bevacizumab 7.5 mg/kg over 90 minutes on Day 1 at the same time as oxaliplatin 130 mg//m\^2 was administered as an IV infusion over 2 hours (Day 1 every 3 weeks) along with capecitabine1000 mg//m\^2 orally BID until Day 14. Treatment with the Cycle 3 dosing regimen continued for a further 13 cycles (i.e. Cycle 16) or until progressive disease or unacceptable toxicity or until the participant withdrew consent
|
|---|---|
|
Age, Continuous
|
57.3 Years
STANDARD_DEVIATION 13.03 • n=99 Participants
|
|
Sex: Female, Male
Female
|
21 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
15 Participants
n=99 Participants
|
PRIMARY outcome
Timeframe: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, and 12 hours post the dose.Population: All patients for whom observations contributing to the relevant assessments were available, who did not experience dose reductions, and for whom dosing was as required by the protocol were included in the corresponding analysis.
AUC0-infinity represents the area under the concentration-time curve of the analyte (5'-DFUR) in plasma over the time interval from 0 extrapolated to infinity. The analyte 5'-DFUR, the direct precursor of 5-fluorouracil (5-FU), is considered to be the most important metabolite of capecitabine in plasma. The unit of measure was nanograms per millilitre per hour (ng/mL \* hr).
Outcome measures
| Measure |
Capecitabine+ Oxaliplatin+ Bevacizumab
n=26 Participants
In Cycle 1, participants received a single oral dose of capecitabine 1000 milligrams per meter square (mg/m\^2 on Day 1 followed by 2-hour intravenous (IV) infusion of oxaliplatin 130 mg/m\^2 on Day 2 followed by oral dosing of capecitabine 1000 mg/m\^2 twice-daily (BID) from Day 5 to Day 14 . In Cycle 2, participants received IV infusion of oxaliplatin 130 mg//m\^2 over 2 hours on Day 1 along with capecitabine 1000 mg/m\^2 orally BID until Day 14. In Cycle 3, participants received IV infusion of bevacizumab 7.5 mg/kg over 90 minutes on Day 1 at the same time as oxaliplatin 130 mg//m\^2 was administered as an IV infusion over 2 hours (Day 1 every 3 weeks) along with capecitabine1000 mg//m\^2 orally BID until Day 14. Treatment with the Cycle 3 dosing regimen continued for a further 13 cycles (i.e. Cycle 16) or until progressive disease or unacceptable toxicity or until the participant withdrew consent
|
|---|---|
|
Area Under The Plasma Concentration-Time Curve From Zero To Infinity (AUC0-Inf) of 5'-Deoxy-5-fluorouridine 5'-(DFUR)
Cycle 1, Day 1
|
13605 ng/mL*hr
Geometric Coefficient of Variation 33
|
|
Area Under The Plasma Concentration-Time Curve From Zero To Infinity (AUC0-Inf) of 5'-Deoxy-5-fluorouridine 5'-(DFUR)
Cycle 2, Day 1
|
12177 ng/mL*hr
Geometric Coefficient of Variation 27
|
|
Area Under The Plasma Concentration-Time Curve From Zero To Infinity (AUC0-Inf) of 5'-Deoxy-5-fluorouridine 5'-(DFUR)
Cycle 3, Day 1
|
11817 ng/mL*hr
Geometric Coefficient of Variation 38
|
PRIMARY outcome
Timeframe: Predose , 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 and 72 hours from the beginning of the 2 hour oxaliplatin infusion on Days 2 to 5 of Cycle 1, and Days 1 to 4 for Cycle 2 and 3.Population: All patients for whom observations contributing to the relevant assessments were available, who did not experience dose reductions, and for whom dosing was as required by the protocol were included in the corresponding analysis.
AUC0-infinity represents the area under the concentration-time curve of the analyte (free platinum) in plasma over the time interval from 0 extrapolated to infinity. AUC0-inf for free platinum was calculated for each participant from the concentration-data obtained on Days 2 to 5 of Cycle 1, and Days 1 to 4 for Cycle 2 and 3. Free platinum is not bound to plasma proteins and is considered to be the most clinically significant measure of pharmacological and toxicological activity.
Outcome measures
| Measure |
Capecitabine+ Oxaliplatin+ Bevacizumab
n=26 Participants
In Cycle 1, participants received a single oral dose of capecitabine 1000 milligrams per meter square (mg/m\^2 on Day 1 followed by 2-hour intravenous (IV) infusion of oxaliplatin 130 mg/m\^2 on Day 2 followed by oral dosing of capecitabine 1000 mg/m\^2 twice-daily (BID) from Day 5 to Day 14 . In Cycle 2, participants received IV infusion of oxaliplatin 130 mg//m\^2 over 2 hours on Day 1 along with capecitabine 1000 mg/m\^2 orally BID until Day 14. In Cycle 3, participants received IV infusion of bevacizumab 7.5 mg/kg over 90 minutes on Day 1 at the same time as oxaliplatin 130 mg//m\^2 was administered as an IV infusion over 2 hours (Day 1 every 3 weeks) along with capecitabine1000 mg//m\^2 orally BID until Day 14. Treatment with the Cycle 3 dosing regimen continued for a further 13 cycles (i.e. Cycle 16) or until progressive disease or unacceptable toxicity or until the participant withdrew consent
|
|---|---|
|
AUC0-inf for Free Platinum
Cycle 1, Day 2
|
10069 ng/mL * hr
Geometric Coefficient of Variation 23
|
|
AUC0-inf for Free Platinum
Cycle 2 , Day 1
|
10537 ng/mL * hr
Geometric Coefficient of Variation 24
|
|
AUC0-inf for Free Platinum
Cycle 3, Day 1.
|
10225 ng/mL * hr
Geometric Coefficient of Variation 23
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, and 12 hours post the dosePopulation: All patients for whom observations contributing to the relevant assessments were available, who did not experience dose reductions, and for whom dosing was as required by the protocol were included in the corresponding analysis.
AUC0-infinity represents the area under the concentration-time curve of the analytes (5'-DFCR, 5-FU, and FBAL) in plasma over the time interval from 0 extrapolated to infinity. After oral administration, capecitabine is first metabolized in the liver to 5'-deoxy-5-fluorocytidine (5'-DFCR), which is then converted to 5'-DFUR, and then catalytically activated to 5-FU.
Outcome measures
| Measure |
Capecitabine+ Oxaliplatin+ Bevacizumab
n=26 Participants
In Cycle 1, participants received a single oral dose of capecitabine 1000 milligrams per meter square (mg/m\^2 on Day 1 followed by 2-hour intravenous (IV) infusion of oxaliplatin 130 mg/m\^2 on Day 2 followed by oral dosing of capecitabine 1000 mg/m\^2 twice-daily (BID) from Day 5 to Day 14 . In Cycle 2, participants received IV infusion of oxaliplatin 130 mg//m\^2 over 2 hours on Day 1 along with capecitabine 1000 mg/m\^2 orally BID until Day 14. In Cycle 3, participants received IV infusion of bevacizumab 7.5 mg/kg over 90 minutes on Day 1 at the same time as oxaliplatin 130 mg//m\^2 was administered as an IV infusion over 2 hours (Day 1 every 3 weeks) along with capecitabine1000 mg//m\^2 orally BID until Day 14. Treatment with the Cycle 3 dosing regimen continued for a further 13 cycles (i.e. Cycle 16) or until progressive disease or unacceptable toxicity or until the participant withdrew consent
|
|---|---|
|
AUC (0-infinity) of Capecitabine and Its Metabolites (5'-DFCR, 5-FU, and FBAL)
Capcetabine , Cycle 1, Day 1
|
5217 ng/mL*hr
Geometric Coefficient of Variation 57
|
|
AUC (0-infinity) of Capecitabine and Its Metabolites (5'-DFCR, 5-FU, and FBAL)
Capcetabine , Cycle 2, Day 1
|
5299 ng/mL*hr
Geometric Coefficient of Variation 54
|
|
AUC (0-infinity) of Capecitabine and Its Metabolites (5'-DFCR, 5-FU, and FBAL)
Capcetabine , Cycle 3, Day 1
|
6130 ng/mL*hr
Geometric Coefficient of Variation 68
|
|
AUC (0-infinity) of Capecitabine and Its Metabolites (5'-DFCR, 5-FU, and FBAL)
5'-DFCR , Cycle 1, Day 1
|
7630 ng/mL*hr
Geometric Coefficient of Variation 76
|
|
AUC (0-infinity) of Capecitabine and Its Metabolites (5'-DFCR, 5-FU, and FBAL)
5'-DFCR , Cycle 2, Day 1
|
6409 ng/mL*hr
Geometric Coefficient of Variation 47
|
|
AUC (0-infinity) of Capecitabine and Its Metabolites (5'-DFCR, 5-FU, and FBAL)
5'-DFCR, Cylce 3, Day 1
|
7989 ng/mL*hr
Geometric Coefficient of Variation 52
|
|
AUC (0-infinity) of Capecitabine and Its Metabolites (5'-DFCR, 5-FU, and FBAL)
5-FU , Cycle 1, Day 1
|
437 ng/mL*hr
Geometric Coefficient of Variation 92
|
|
AUC (0-infinity) of Capecitabine and Its Metabolites (5'-DFCR, 5-FU, and FBAL)
5-FU , Cycle 2, Day 1
|
355 ng/mL*hr
Geometric Coefficient of Variation 50
|
|
AUC (0-infinity) of Capecitabine and Its Metabolites (5'-DFCR, 5-FU, and FBAL)
5-FU , Cycle 3, Day 1
|
343 ng/mL*hr
Geometric Coefficient of Variation 86
|
|
AUC (0-infinity) of Capecitabine and Its Metabolites (5'-DFCR, 5-FU, and FBAL)
FBAL , Cycle 1, Day 1
|
17904 ng/mL*hr
Geometric Coefficient of Variation 27
|
|
AUC (0-infinity) of Capecitabine and Its Metabolites (5'-DFCR, 5-FU, and FBAL)
FBAL , Cycle 2, Day 1
|
17413 ng/mL*hr
Geometric Coefficient of Variation 26
|
|
AUC (0-infinity) of Capecitabine and Its Metabolites (5'-DFCR, 5-FU, and FBAL)
FBAL , Cycle 3, Day 1
|
17356 ng/mL*hr
Geometric Coefficient of Variation 34
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, and 12 hours post the dosePopulation: All patients for whom observations contributing to the relevant assessments were available, who did not experience dose reductions, and for whom dosing was as required by the protocol were included in the corresponding analysis.
Area under the plasma concentration-time curve from time zero to the time of the last measurable plasma concentration time point of capecitabine and its metabolites (5'-DFUR, 5'-DFCR, 5 FU, and FBAL).
Outcome measures
| Measure |
Capecitabine+ Oxaliplatin+ Bevacizumab
n=26 Participants
In Cycle 1, participants received a single oral dose of capecitabine 1000 milligrams per meter square (mg/m\^2 on Day 1 followed by 2-hour intravenous (IV) infusion of oxaliplatin 130 mg/m\^2 on Day 2 followed by oral dosing of capecitabine 1000 mg/m\^2 twice-daily (BID) from Day 5 to Day 14 . In Cycle 2, participants received IV infusion of oxaliplatin 130 mg//m\^2 over 2 hours on Day 1 along with capecitabine 1000 mg/m\^2 orally BID until Day 14. In Cycle 3, participants received IV infusion of bevacizumab 7.5 mg/kg over 90 minutes on Day 1 at the same time as oxaliplatin 130 mg//m\^2 was administered as an IV infusion over 2 hours (Day 1 every 3 weeks) along with capecitabine1000 mg//m\^2 orally BID until Day 14. Treatment with the Cycle 3 dosing regimen continued for a further 13 cycles (i.e. Cycle 16) or until progressive disease or unacceptable toxicity or until the participant withdrew consent
|
|---|---|
|
AUC0-last of Capecitabine and Its Metabolites (5'-DFUR, 5'-DFCR, 5 FU, and FBAL)
5' DFUR, Cycle 3, Day 1
|
11618 ng/mL*hr
Geometric Coefficient of Variation 38
|
|
AUC0-last of Capecitabine and Its Metabolites (5'-DFUR, 5'-DFCR, 5 FU, and FBAL)
Capecitabine, Cycle 1, Day 1
|
5201 ng/mL*hr
Geometric Coefficient of Variation 57
|
|
AUC0-last of Capecitabine and Its Metabolites (5'-DFUR, 5'-DFCR, 5 FU, and FBAL)
Capecitabine, Cycle 2, Day 1
|
5273 ng/mL*hr
Geometric Coefficient of Variation 54
|
|
AUC0-last of Capecitabine and Its Metabolites (5'-DFUR, 5'-DFCR, 5 FU, and FBAL)
Capecitabine, Cycle 3, Day 1
|
6093 ng/mL*hr
Geometric Coefficient of Variation 68
|
|
AUC0-last of Capecitabine and Its Metabolites (5'-DFUR, 5'-DFCR, 5 FU, and FBAL)
5'-DFCR, Cycle 1, Day 1
|
6150 ng/mL*hr
Geometric Coefficient of Variation 80
|
|
AUC0-last of Capecitabine and Its Metabolites (5'-DFUR, 5'-DFCR, 5 FU, and FBAL)
5'-DFCR, Cycle 2 , Day 1
|
6378 ng/mL*hr
Geometric Coefficient of Variation 47
|
|
AUC0-last of Capecitabine and Its Metabolites (5'-DFUR, 5'-DFCR, 5 FU, and FBAL)
5'-DFCR, Cycle 3, Day 1
|
7909 ng/mL*hr
Geometric Coefficient of Variation 52
|
|
AUC0-last of Capecitabine and Its Metabolites (5'-DFUR, 5'-DFCR, 5 FU, and FBAL)
5-FU, Cycle 1, Day 1
|
433 ng/mL*hr
Geometric Coefficient of Variation 92
|
|
AUC0-last of Capecitabine and Its Metabolites (5'-DFUR, 5'-DFCR, 5 FU, and FBAL)
5-FU, Cycle 2, Day 1
|
350 ng/mL*hr
Geometric Coefficient of Variation 51
|
|
AUC0-last of Capecitabine and Its Metabolites (5'-DFUR, 5'-DFCR, 5 FU, and FBAL)
5-FU, Cycle 3, Day 1
|
336 ng/mL*hr
Geometric Coefficient of Variation 84
|
|
AUC0-last of Capecitabine and Its Metabolites (5'-DFUR, 5'-DFCR, 5 FU, and FBAL)
FBAL, Cycle 1, Day 1
|
16773 ng/mL*hr
Geometric Coefficient of Variation 26
|
|
AUC0-last of Capecitabine and Its Metabolites (5'-DFUR, 5'-DFCR, 5 FU, and FBAL)
FBAL, Cycle 2, Day 1
|
15992 ng/mL*hr
Geometric Coefficient of Variation 26
|
|
AUC0-last of Capecitabine and Its Metabolites (5'-DFUR, 5'-DFCR, 5 FU, and FBAL)
FBAL, Cycle 3, Day 1
|
14947 ng/mL*hr
Geometric Coefficient of Variation 31
|
|
AUC0-last of Capecitabine and Its Metabolites (5'-DFUR, 5'-DFCR, 5 FU, and FBAL)
5' DFUR , Cycle 1, Day 1
|
13503 ng/mL*hr
Geometric Coefficient of Variation 33
|
|
AUC0-last of Capecitabine and Its Metabolites (5'-DFUR, 5'-DFCR, 5 FU, and FBAL)
5' DFUR, Cycle 2 , Day 1
|
12057 ng/mL*hr
Geometric Coefficient of Variation 28
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, and 12 hours post the dosePopulation: All patients for whom observations contributing to the relevant assessments were available, who did not experience dose reductions, and for whom dosing was as required by the protocol were included in the corresponding analysis.
Cmax is defined as maximum observed analyte concentration of capecitabine and its metabolites (5'-DFUR, 5'-DFCR, 5 FU, and FBAL)
Outcome measures
| Measure |
Capecitabine+ Oxaliplatin+ Bevacizumab
n=26 Participants
In Cycle 1, participants received a single oral dose of capecitabine 1000 milligrams per meter square (mg/m\^2 on Day 1 followed by 2-hour intravenous (IV) infusion of oxaliplatin 130 mg/m\^2 on Day 2 followed by oral dosing of capecitabine 1000 mg/m\^2 twice-daily (BID) from Day 5 to Day 14 . In Cycle 2, participants received IV infusion of oxaliplatin 130 mg//m\^2 over 2 hours on Day 1 along with capecitabine 1000 mg/m\^2 orally BID until Day 14. In Cycle 3, participants received IV infusion of bevacizumab 7.5 mg/kg over 90 minutes on Day 1 at the same time as oxaliplatin 130 mg//m\^2 was administered as an IV infusion over 2 hours (Day 1 every 3 weeks) along with capecitabine1000 mg//m\^2 orally BID until Day 14. Treatment with the Cycle 3 dosing regimen continued for a further 13 cycles (i.e. Cycle 16) or until progressive disease or unacceptable toxicity or until the participant withdrew consent
|
|---|---|
|
Maximum Plasma Concentration (Cmax) of Capecitabine and Its Metabolites (5'-DFUR, 5'-DFCR, 5 FU, and FBAL)
5'-DFUR, Cycle 1, Day 1
|
8847 ng/mL
Geometric Coefficient of Variation 48
|
|
Maximum Plasma Concentration (Cmax) of Capecitabine and Its Metabolites (5'-DFUR, 5'-DFCR, 5 FU, and FBAL)
5'-DFUR , Cycle 2, Day 1
|
6545 ng/mL
Geometric Coefficient of Variation 48
|
|
Maximum Plasma Concentration (Cmax) of Capecitabine and Its Metabolites (5'-DFUR, 5'-DFCR, 5 FU, and FBAL)
5'-DFUR , Cycle 3, Day 1
|
5693 ng/mL
Geometric Coefficient of Variation 54
|
|
Maximum Plasma Concentration (Cmax) of Capecitabine and Its Metabolites (5'-DFUR, 5'-DFCR, 5 FU, and FBAL)
Capecitabine, Cycle 1, Day 1
|
4930 ng/mL
Geometric Coefficient of Variation 72
|
|
Maximum Plasma Concentration (Cmax) of Capecitabine and Its Metabolites (5'-DFUR, 5'-DFCR, 5 FU, and FBAL)
Capecitabine, Cycle 2, Day 1
|
4065 ng/mL
Geometric Coefficient of Variation 73
|
|
Maximum Plasma Concentration (Cmax) of Capecitabine and Its Metabolites (5'-DFUR, 5'-DFCR, 5 FU, and FBAL)
Capecitabine, Cycle 3, Day 1
|
4167 ng/mL
Geometric Coefficient of Variation 81
|
|
Maximum Plasma Concentration (Cmax) of Capecitabine and Its Metabolites (5'-DFUR, 5'-DFCR, 5 FU, and FBAL)
5' DFCR, Cycle 1, Day 1
|
3902 ng/mL
Geometric Coefficient of Variation 78
|
|
Maximum Plasma Concentration (Cmax) of Capecitabine and Its Metabolites (5'-DFUR, 5'-DFCR, 5 FU, and FBAL)
5' DFCR, Cycle 2, Day 1
|
3407 ng/mL
Geometric Coefficient of Variation 66
|
|
Maximum Plasma Concentration (Cmax) of Capecitabine and Its Metabolites (5'-DFUR, 5'-DFCR, 5 FU, and FBAL)
5' DFCR , Cycle 3, Day 1
|
3747 ng/mL
Geometric Coefficient of Variation 69
|
|
Maximum Plasma Concentration (Cmax) of Capecitabine and Its Metabolites (5'-DFUR, 5'-DFCR, 5 FU, and FBAL)
5-FU, Cycle 1 , Day 1
|
292 ng/mL
Geometric Coefficient of Variation 63
|
|
Maximum Plasma Concentration (Cmax) of Capecitabine and Its Metabolites (5'-DFUR, 5'-DFCR, 5 FU, and FBAL)
5-FU, Cycle 2, Day 1
|
216 ng/mL
Geometric Coefficient of Variation 63
|
|
Maximum Plasma Concentration (Cmax) of Capecitabine and Its Metabolites (5'-DFUR, 5'-DFCR, 5 FU, and FBAL)
5-FU, Cycle 3, Day 1
|
168 ng/mL
Geometric Coefficient of Variation 83
|
|
Maximum Plasma Concentration (Cmax) of Capecitabine and Its Metabolites (5'-DFUR, 5'-DFCR, 5 FU, and FBAL)
FBAL, Cycle 1, Day 1
|
3970 ng/mL
Geometric Coefficient of Variation 19
|
|
Maximum Plasma Concentration (Cmax) of Capecitabine and Its Metabolites (5'-DFUR, 5'-DFCR, 5 FU, and FBAL)
FBAL, Cycle 2, Day 1
|
3627 ng/mL
Geometric Coefficient of Variation 27
|
|
Maximum Plasma Concentration (Cmax) of Capecitabine and Its Metabolites (5'-DFUR, 5'-DFCR, 5 FU, and FBAL)
FBAL, Cycle 3, Day 1
|
3292 ng/mL
Geometric Coefficient of Variation 34
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, and 12 hours post the dosePopulation: All patients for whom observations contributing to the relevant assessments were available, who did not experience dose reductions, and for whom dosing was as required by the protocol were included in the corresponding analysis.
t1/2 Beta is the time measured for the plasma concentration to decrease by 1 half to its original concentration of capecitabine and its metabolites (5'-DFUR , 5'-DFCR, 5 FU, and FBAL)
Outcome measures
| Measure |
Capecitabine+ Oxaliplatin+ Bevacizumab
n=26 Participants
In Cycle 1, participants received a single oral dose of capecitabine 1000 milligrams per meter square (mg/m\^2 on Day 1 followed by 2-hour intravenous (IV) infusion of oxaliplatin 130 mg/m\^2 on Day 2 followed by oral dosing of capecitabine 1000 mg/m\^2 twice-daily (BID) from Day 5 to Day 14 . In Cycle 2, participants received IV infusion of oxaliplatin 130 mg//m\^2 over 2 hours on Day 1 along with capecitabine 1000 mg/m\^2 orally BID until Day 14. In Cycle 3, participants received IV infusion of bevacizumab 7.5 mg/kg over 90 minutes on Day 1 at the same time as oxaliplatin 130 mg//m\^2 was administered as an IV infusion over 2 hours (Day 1 every 3 weeks) along with capecitabine1000 mg//m\^2 orally BID until Day 14. Treatment with the Cycle 3 dosing regimen continued for a further 13 cycles (i.e. Cycle 16) or until progressive disease or unacceptable toxicity or until the participant withdrew consent
|
|---|---|
|
Elimination Half-life Period (t1/2 Beta) of Capecitabine and Its Metabolites (5'-DFUR , 5'-DFCR, 5 FU, and FBAL)
5' DFUR; Cycle 1, Day 1
|
0.65 hour
Geometric Coefficient of Variation 19
|
|
Elimination Half-life Period (t1/2 Beta) of Capecitabine and Its Metabolites (5'-DFUR , 5'-DFCR, 5 FU, and FBAL)
5' DFUR, Cycle 2 , Day 1
|
0.64 hour
Geometric Coefficient of Variation 49
|
|
Elimination Half-life Period (t1/2 Beta) of Capecitabine and Its Metabolites (5'-DFUR , 5'-DFCR, 5 FU, and FBAL)
5' DFUR, Cycle 3, Day 1
|
0.75 hour
Geometric Coefficient of Variation 39
|
|
Elimination Half-life Period (t1/2 Beta) of Capecitabine and Its Metabolites (5'-DFUR , 5'-DFCR, 5 FU, and FBAL)
Capecitabine, Cycle 1, Day 1
|
0.37 hour
Geometric Coefficient of Variation 52
|
|
Elimination Half-life Period (t1/2 Beta) of Capecitabine and Its Metabolites (5'-DFUR , 5'-DFCR, 5 FU, and FBAL)
Capecitabine, Cycle 2, Day 1
|
0.51 hour
Geometric Coefficient of Variation 55
|
|
Elimination Half-life Period (t1/2 Beta) of Capecitabine and Its Metabolites (5'-DFUR , 5'-DFCR, 5 FU, and FBAL)
Capecitabine, Cycle 3, Day 1
|
0.56 hour
Geometric Coefficient of Variation 42
|
|
Elimination Half-life Period (t1/2 Beta) of Capecitabine and Its Metabolites (5'-DFUR , 5'-DFCR, 5 FU, and FBAL)
5'-DFCR, Cycle 1, Day 1
|
0.71 hour
Geometric Coefficient of Variation 33
|
|
Elimination Half-life Period (t1/2 Beta) of Capecitabine and Its Metabolites (5'-DFUR , 5'-DFCR, 5 FU, and FBAL)
5'-DFCR, Cycle 2 , Day 1
|
0.75 hour
Geometric Coefficient of Variation 32
|
|
Elimination Half-life Period (t1/2 Beta) of Capecitabine and Its Metabolites (5'-DFUR , 5'-DFCR, 5 FU, and FBAL)
5'-DFCR, Cycle 3, Day 1
|
0.79 hour
Geometric Coefficient of Variation 24
|
|
Elimination Half-life Period (t1/2 Beta) of Capecitabine and Its Metabolites (5'-DFUR , 5'-DFCR, 5 FU, and FBAL)
5-FU, Cycle 1, Day 1
|
0.61 hour
Geometric Coefficient of Variation 20
|
|
Elimination Half-life Period (t1/2 Beta) of Capecitabine and Its Metabolites (5'-DFUR , 5'-DFCR, 5 FU, and FBAL)
5-FU, Cycle 2, Day 1
|
0.67 hour
Geometric Coefficient of Variation 61
|
|
Elimination Half-life Period (t1/2 Beta) of Capecitabine and Its Metabolites (5'-DFUR , 5'-DFCR, 5 FU, and FBAL)
5-FU, Cycle 3, Day 1
|
0.71 hour
Geometric Coefficient of Variation 31
|
|
Elimination Half-life Period (t1/2 Beta) of Capecitabine and Its Metabolites (5'-DFUR , 5'-DFCR, 5 FU, and FBAL)
FBAL, Cycle 1, Day 1
|
2.77 hour
Geometric Coefficient of Variation 19
|
|
Elimination Half-life Period (t1/2 Beta) of Capecitabine and Its Metabolites (5'-DFUR , 5'-DFCR, 5 FU, and FBAL)
FBAL, Cycle 2, Day 1
|
2.68 hour
Geometric Coefficient of Variation 26
|
|
Elimination Half-life Period (t1/2 Beta) of Capecitabine and Its Metabolites (5'-DFUR , 5'-DFCR, 5 FU, and FBAL)
FBAL, Cycle 3, Day 1
|
2.64 hour
Geometric Coefficient of Variation 33
|
SECONDARY outcome
Timeframe: Pre-dose, and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 and 72 hours from the beginning of the two hour oxaliplatin infusion on Days 2 to 5 of Cycle 1, and Days 1 to 4 for Cycle 2 and 3Population: All patients for whom observations contributing to the relevant assessments were available, who did not experience dose reductions, and for whom dosing was as required by the protocol were included in the corresponding analysis.
AUC0-infinity represents the area under the concentration-time curve of the analyte (total platinum) in plasma over the time interval from 0 extrapolated to infinity.
Outcome measures
| Measure |
Capecitabine+ Oxaliplatin+ Bevacizumab
n=26 Participants
In Cycle 1, participants received a single oral dose of capecitabine 1000 milligrams per meter square (mg/m\^2 on Day 1 followed by 2-hour intravenous (IV) infusion of oxaliplatin 130 mg/m\^2 on Day 2 followed by oral dosing of capecitabine 1000 mg/m\^2 twice-daily (BID) from Day 5 to Day 14 . In Cycle 2, participants received IV infusion of oxaliplatin 130 mg//m\^2 over 2 hours on Day 1 along with capecitabine 1000 mg/m\^2 orally BID until Day 14. In Cycle 3, participants received IV infusion of bevacizumab 7.5 mg/kg over 90 minutes on Day 1 at the same time as oxaliplatin 130 mg//m\^2 was administered as an IV infusion over 2 hours (Day 1 every 3 weeks) along with capecitabine1000 mg//m\^2 orally BID until Day 14. Treatment with the Cycle 3 dosing regimen continued for a further 13 cycles (i.e. Cycle 16) or until progressive disease or unacceptable toxicity or until the participant withdrew consent
|
|---|---|
|
AUC0-infinity for Total Platinum
Cycle 1, Day 2
|
139329 ng/mL* hr
Geometric Coefficient of Variation 24
|
|
AUC0-infinity for Total Platinum
Cycle 2, Day 1
|
167610 ng/mL* hr
Geometric Coefficient of Variation 17
|
|
AUC0-infinity for Total Platinum
Cycle 3, Day 1
|
186268 ng/mL* hr
Geometric Coefficient of Variation 21
|
SECONDARY outcome
Timeframe: pre-dose, and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 and 72 hours from the beginning of the two hour oxaliplatin infusion on Days 2 to 5 of Cycle 1, and Days 1 to 4 for Cycle 2 and 3.Population: All patients for whom observations contributing to the relevant assessments were available, who did not experience dose reductions, and for whom dosing was as required by the protocol were included in the corresponding analysis.
Area under the plasma concentration-time curve from time zero to the time of the last measurable plasma concentration time point of Total And Free Platinum.
Outcome measures
| Measure |
Capecitabine+ Oxaliplatin+ Bevacizumab
n=26 Participants
In Cycle 1, participants received a single oral dose of capecitabine 1000 milligrams per meter square (mg/m\^2 on Day 1 followed by 2-hour intravenous (IV) infusion of oxaliplatin 130 mg/m\^2 on Day 2 followed by oral dosing of capecitabine 1000 mg/m\^2 twice-daily (BID) from Day 5 to Day 14 . In Cycle 2, participants received IV infusion of oxaliplatin 130 mg//m\^2 over 2 hours on Day 1 along with capecitabine 1000 mg/m\^2 orally BID until Day 14. In Cycle 3, participants received IV infusion of bevacizumab 7.5 mg/kg over 90 minutes on Day 1 at the same time as oxaliplatin 130 mg//m\^2 was administered as an IV infusion over 2 hours (Day 1 every 3 weeks) along with capecitabine1000 mg//m\^2 orally BID until Day 14. Treatment with the Cycle 3 dosing regimen continued for a further 13 cycles (i.e. Cycle 16) or until progressive disease or unacceptable toxicity or until the participant withdrew consent
|
|---|---|
|
AUC0-last of Total And Free Platinum
Total Platinum: Cycle 1, Day 2
|
85406 ng/mL* hr
Geometric Coefficient of Variation 20
|
|
AUC0-last of Total And Free Platinum
Total Platinum: Cycle 2, Day 1
|
97083 ng/mL* hr
Geometric Coefficient of Variation 12
|
|
AUC0-last of Total And Free Platinum
Total Platinum: Cycle 3, Day 1
|
97011 ng/mL* hr
Geometric Coefficient of Variation 17
|
|
AUC0-last of Total And Free Platinum
Free Platinum: Cycle 1, Day 2
|
9399 ng/mL* hr
Geometric Coefficient of Variation 24
|
|
AUC0-last of Total And Free Platinum
Free Platinum: Cycle 2, Day 1
|
9818 ng/mL* hr
Geometric Coefficient of Variation 25
|
|
AUC0-last of Total And Free Platinum
Free Platinum: Cycle 3, Day 1
|
9604 ng/mL* hr
Geometric Coefficient of Variation 22
|
SECONDARY outcome
Timeframe: Pre-dose, and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 and 72 hours from the beginning of the two hour oxaliplatin infusion on Days 2 to 5 of Cycle 1, and Days 1 to 4 for Cycle 2 and 3.Population: All patients for whom observations contributing to the relevant assessments were available, who did not experience dose reductions, and for whom dosing was as required by the protocol were included in the corresponding analysis.
Cmax is defined as maximum observed analyte concentration of Total And Free Platinum.
Outcome measures
| Measure |
Capecitabine+ Oxaliplatin+ Bevacizumab
n=26 Participants
In Cycle 1, participants received a single oral dose of capecitabine 1000 milligrams per meter square (mg/m\^2 on Day 1 followed by 2-hour intravenous (IV) infusion of oxaliplatin 130 mg/m\^2 on Day 2 followed by oral dosing of capecitabine 1000 mg/m\^2 twice-daily (BID) from Day 5 to Day 14 . In Cycle 2, participants received IV infusion of oxaliplatin 130 mg//m\^2 over 2 hours on Day 1 along with capecitabine 1000 mg/m\^2 orally BID until Day 14. In Cycle 3, participants received IV infusion of bevacizumab 7.5 mg/kg over 90 minutes on Day 1 at the same time as oxaliplatin 130 mg//m\^2 was administered as an IV infusion over 2 hours (Day 1 every 3 weeks) along with capecitabine1000 mg//m\^2 orally BID until Day 14. Treatment with the Cycle 3 dosing regimen continued for a further 13 cycles (i.e. Cycle 16) or until progressive disease or unacceptable toxicity or until the participant withdrew consent
|
|---|---|
|
Cmax of Total And Free Platinum
Total Platinum: Cycle 1, Day 2
|
3652 ng/mL
Geometric Coefficient of Variation 14
|
|
Cmax of Total And Free Platinum
Total Platinum: Cycle 2, Day 1
|
3741 ng/mL
Geometric Coefficient of Variation 19
|
|
Cmax of Total And Free Platinum
Total Platinum: Cycle 3, Day 1
|
3706 ng/mL
Geometric Coefficient of Variation 21
|
|
Cmax of Total And Free Platinum
Free Platinum: Cycle 1, Day 2
|
1818 ng/mL
Geometric Coefficient of Variation 27
|
|
Cmax of Total And Free Platinum
Free Platinum: Cycle 2, Day 1
|
1840 ng/mL
Geometric Coefficient of Variation 36
|
|
Cmax of Total And Free Platinum
Free Platinum: Cycle 3, Day 1
|
1813 ng/mL
Geometric Coefficient of Variation 30
|
SECONDARY outcome
Timeframe: Pre-dose, and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 and 72 hours from the beginning of the two hour oxaliplatin infusion on Days 2 to 5 of Cycle 1, and Days 1 to 4 for Cycle 2 and 3Population: All patients for whom observations contributing to the relevant assessments were available, who did not experience dose reductions, and for whom dosing was as required by the protocol were included in the corresponding analysis.
T1/2 beta is the time measured for the plasma concentration to decrease by 1 half to its original concentration of total and free platinum.
Outcome measures
| Measure |
Capecitabine+ Oxaliplatin+ Bevacizumab
n=26 Participants
In Cycle 1, participants received a single oral dose of capecitabine 1000 milligrams per meter square (mg/m\^2 on Day 1 followed by 2-hour intravenous (IV) infusion of oxaliplatin 130 mg/m\^2 on Day 2 followed by oral dosing of capecitabine 1000 mg/m\^2 twice-daily (BID) from Day 5 to Day 14 . In Cycle 2, participants received IV infusion of oxaliplatin 130 mg//m\^2 over 2 hours on Day 1 along with capecitabine 1000 mg/m\^2 orally BID until Day 14. In Cycle 3, participants received IV infusion of bevacizumab 7.5 mg/kg over 90 minutes on Day 1 at the same time as oxaliplatin 130 mg//m\^2 was administered as an IV infusion over 2 hours (Day 1 every 3 weeks) along with capecitabine1000 mg//m\^2 orally BID until Day 14. Treatment with the Cycle 3 dosing regimen continued for a further 13 cycles (i.e. Cycle 16) or until progressive disease or unacceptable toxicity or until the participant withdrew consent
|
|---|---|
|
T1/2 Beta of Total And Free Platinum
Total Platinum: Cycle 1, Day 2
|
48.70 hour
Geometric Coefficient of Variation 30
|
|
T1/2 Beta of Total And Free Platinum
Total Platinum: Cycle 2, Day 1
|
55.73 hour
Geometric Coefficient of Variation 24
|
|
T1/2 Beta of Total And Free Platinum
Total Platinum: Cycle 3, Day 1
|
67.28 hour
Geometric Coefficient of Variation 26
|
|
T1/2 Beta of Total And Free Platinum
Free Platinum: Cycle 1, Day 2
|
17.64 hour
Geometric Coefficient of Variation 10
|
|
T1/2 Beta of Total And Free Platinum
Free Platinum: Cycle 2, Day 1
|
18.41 hour
Geometric Coefficient of Variation 9
|
|
T1/2 Beta of Total And Free Platinum
Free Platinum: Cycle 3, Day 1
|
18.47 hour
Geometric Coefficient of Variation 10.90
|
SECONDARY outcome
Timeframe: Pre-dose, and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 and 72 hoursPopulation: All patients for whom observations contributing to the relevant assessments were available, who did not experience dose reductions, and for whom dosing was as required by the protocol were included in the corresponding analysis.
VSS is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Steady state volume of distribution (Vss) is the apparent volume of distribution at steady-state.
Outcome measures
| Measure |
Capecitabine+ Oxaliplatin+ Bevacizumab
n=26 Participants
In Cycle 1, participants received a single oral dose of capecitabine 1000 milligrams per meter square (mg/m\^2 on Day 1 followed by 2-hour intravenous (IV) infusion of oxaliplatin 130 mg/m\^2 on Day 2 followed by oral dosing of capecitabine 1000 mg/m\^2 twice-daily (BID) from Day 5 to Day 14 . In Cycle 2, participants received IV infusion of oxaliplatin 130 mg//m\^2 over 2 hours on Day 1 along with capecitabine 1000 mg/m\^2 orally BID until Day 14. In Cycle 3, participants received IV infusion of bevacizumab 7.5 mg/kg over 90 minutes on Day 1 at the same time as oxaliplatin 130 mg//m\^2 was administered as an IV infusion over 2 hours (Day 1 every 3 weeks) along with capecitabine1000 mg//m\^2 orally BID until Day 14. Treatment with the Cycle 3 dosing regimen continued for a further 13 cycles (i.e. Cycle 16) or until progressive disease or unacceptable toxicity or until the participant withdrew consent
|
|---|---|
|
Volume of Distribution at Steady State (VSS) of Total And Free Platinum
Total Platinum: Cycle 1, Day 2
|
109007 mL
Geometric Coefficient of Variation 23
|
|
Volume of Distribution at Steady State (VSS) of Total And Free Platinum
Total Platinum: Cycle 2, Day 1
|
105097 mL
Geometric Coefficient of Variation 21
|
|
Volume of Distribution at Steady State (VSS) of Total And Free Platinum
Total Platinum: Cycle 3, Day 1
|
112141 mL
Geometric Coefficient of Variation 21
|
|
Volume of Distribution at Steady State (VSS) of Total And Free Platinum
Free Platinum: Cycle 1, Day 2
|
387158 mL
Geometric Coefficient of Variation 23
|
|
Volume of Distribution at Steady State (VSS) of Total And Free Platinum
Free Platinum: Cycle 2, Day 1
|
389193 mL
Geometric Coefficient of Variation 29
|
|
Volume of Distribution at Steady State (VSS) of Total And Free Platinum
Free Platinum: Cycle 3, Day 1
|
401040 mL
Geometric Coefficient of Variation 24
|
SECONDARY outcome
Timeframe: Pre-dose, and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 and 72 hours from the beginning of the two hour oxaliplatin infusion on Days 2 to 5 of Cycle 1, and Days 1 to 4 for Cycle 2 and 3Population: All patients for whom observations contributing to the relevant assessments were available, who did not experience dose reductions, and for whom dosing was as required by the protocol were included in the corresponding analysis.
CL is a calculation of the rate at which a drug is removed from the body via renal, hepatic and other clearance pathways, expressed as volume (milliliters) per unit of time (hour).
Outcome measures
| Measure |
Capecitabine+ Oxaliplatin+ Bevacizumab
n=26 Participants
In Cycle 1, participants received a single oral dose of capecitabine 1000 milligrams per meter square (mg/m\^2 on Day 1 followed by 2-hour intravenous (IV) infusion of oxaliplatin 130 mg/m\^2 on Day 2 followed by oral dosing of capecitabine 1000 mg/m\^2 twice-daily (BID) from Day 5 to Day 14 . In Cycle 2, participants received IV infusion of oxaliplatin 130 mg//m\^2 over 2 hours on Day 1 along with capecitabine 1000 mg/m\^2 orally BID until Day 14. In Cycle 3, participants received IV infusion of bevacizumab 7.5 mg/kg over 90 minutes on Day 1 at the same time as oxaliplatin 130 mg//m\^2 was administered as an IV infusion over 2 hours (Day 1 every 3 weeks) along with capecitabine1000 mg//m\^2 orally BID until Day 14. Treatment with the Cycle 3 dosing regimen continued for a further 13 cycles (i.e. Cycle 16) or until progressive disease or unacceptable toxicity or until the participant withdrew consent
|
|---|---|
|
Clearance of Total And Free Platinum
Total Platinum: Cycle 1, Day 2
|
1603 mL/Hr
Geometric Coefficient of Variation 78
|
|
Clearance of Total And Free Platinum
Total Platinum: Cycle 2, Day 1
|
1331 mL/Hr
Geometric Coefficient of Variation 22
|
|
Clearance of Total And Free Platinum
Total Platinum: Cycle 3, Day 1
|
1198 mL/Hr
Geometric Coefficient of Variation 25
|
|
Clearance of Total And Free Platinum
Free Platinum: Cycle 1, Day 2
|
22183 mL/Hr
Geometric Coefficient of Variation 23
|
|
Clearance of Total And Free Platinum
Free Platinum: Cycle 2, Day 1
|
21176 mL/Hr
Geometric Coefficient of Variation 26
|
|
Clearance of Total And Free Platinum
Free Platinum: Cycle 3, Day 1
|
21823 mL/Hr
Geometric Coefficient of Variation 23
|
SECONDARY outcome
Timeframe: Approximately 3 Years (up to 28 days after the last intake of study medication)Population: All 36 participants who received at least one dose of capecitabine.
An adverse event is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product. This includes any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Pre-existing conditions which worsened during the study were also to be reported as AEs.
Outcome measures
| Measure |
Capecitabine+ Oxaliplatin+ Bevacizumab
n=36 Participants
In Cycle 1, participants received a single oral dose of capecitabine 1000 milligrams per meter square (mg/m\^2 on Day 1 followed by 2-hour intravenous (IV) infusion of oxaliplatin 130 mg/m\^2 on Day 2 followed by oral dosing of capecitabine 1000 mg/m\^2 twice-daily (BID) from Day 5 to Day 14 . In Cycle 2, participants received IV infusion of oxaliplatin 130 mg//m\^2 over 2 hours on Day 1 along with capecitabine 1000 mg/m\^2 orally BID until Day 14. In Cycle 3, participants received IV infusion of bevacizumab 7.5 mg/kg over 90 minutes on Day 1 at the same time as oxaliplatin 130 mg//m\^2 was administered as an IV infusion over 2 hours (Day 1 every 3 weeks) along with capecitabine1000 mg//m\^2 orally BID until Day 14. Treatment with the Cycle 3 dosing regimen continued for a further 13 cycles (i.e. Cycle 16) or until progressive disease or unacceptable toxicity or until the participant withdrew consent
|
|---|---|
|
Number Of Participants With Adverse Events (AEs)
Any AE
|
36 Participants
|
|
Number Of Participants With Adverse Events (AEs)
Any SAE
|
16 Participants
|
SECONDARY outcome
Timeframe: Up to 28 days after last chemotherapy administrationPopulation: All 36 participants who received at least one dose of capecitabine.
Number of participants with marked laboratory abnormalities (hematology, coagulation, liver function, renal function, protein, electrolytes, miscellaneous).
Outcome measures
| Measure |
Capecitabine+ Oxaliplatin+ Bevacizumab
n=36 Participants
In Cycle 1, participants received a single oral dose of capecitabine 1000 milligrams per meter square (mg/m\^2 on Day 1 followed by 2-hour intravenous (IV) infusion of oxaliplatin 130 mg/m\^2 on Day 2 followed by oral dosing of capecitabine 1000 mg/m\^2 twice-daily (BID) from Day 5 to Day 14 . In Cycle 2, participants received IV infusion of oxaliplatin 130 mg//m\^2 over 2 hours on Day 1 along with capecitabine 1000 mg/m\^2 orally BID until Day 14. In Cycle 3, participants received IV infusion of bevacizumab 7.5 mg/kg over 90 minutes on Day 1 at the same time as oxaliplatin 130 mg//m\^2 was administered as an IV infusion over 2 hours (Day 1 every 3 weeks) along with capecitabine1000 mg//m\^2 orally BID until Day 14. Treatment with the Cycle 3 dosing regimen continued for a further 13 cycles (i.e. Cycle 16) or until progressive disease or unacceptable toxicity or until the participant withdrew consent
|
|---|---|
|
Marked Laboratory Abnormalities
Hematocrit - high
|
2 Participants
|
|
Marked Laboratory Abnormalities
Hematocrit - low
|
5 Participants
|
|
Marked Laboratory Abnormalities
Hemoglobin - low
|
6 Participants
|
|
Marked Laboratory Abnormalities
Platelets - high
|
1 Participants
|
|
Marked Laboratory Abnormalities
Platelets - low
|
9 Participants
|
|
Marked Laboratory Abnormalities
RBC - low
|
12 Participants
|
|
Marked Laboratory Abnormalities
WBC - high
|
1 Participants
|
|
Marked Laboratory Abnormalities
WBC - low
|
7 Participants
|
|
Marked Laboratory Abnormalities
Neutrophils - high
|
1 Participants
|
|
Marked Laboratory Abnormalities
Neutrophils - low
|
3 Participants
|
|
Marked Laboratory Abnormalities
PT (INR) - high
|
2 Participants
|
|
Marked Laboratory Abnormalities
ASAT (SGOT) - high
|
6 Participants
|
|
Marked Laboratory Abnormalities
LDH - high
|
2 Participants
|
|
Marked Laboratory Abnormalities
ALAT (SGPT) - high
|
7 Participants
|
|
Marked Laboratory Abnormalities
Alk. Phos. - high
|
6 Participants
|
|
Marked Laboratory Abnormalities
Dir. Bilirubin - high
|
3 Participants
|
|
Marked Laboratory Abnormalities
Total Bilirubin - high
|
2 Participants
|
|
Marked Laboratory Abnormalities
Creatinine - high
|
0 Participants
|
|
Marked Laboratory Abnormalities
Albumin - low
|
4 Participants
|
|
Marked Laboratory Abnormalities
Potassium - low
|
2 Participants
|
|
Marked Laboratory Abnormalities
Sodium - low
|
2 Participants
|
|
Marked Laboratory Abnormalities
Calcium - low
|
1 Participants
|
|
Marked Laboratory Abnormalities
Glucose Fasting - high
|
4 Participants
|
Adverse Events
Capecitabine+ Oxaliplatin+ Bevacizumab
Serious events: 16 serious events
Other events: 36 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Capecitabine+ Oxaliplatin+ Bevacizumab
n=36 participants at risk
In Cycle 1, participants received a single oral dose of capecitabine 1000 milligrams per meter square (mg/m\^2 on Day 1 followed by 2-hour intravenous (IV) infusion of oxaliplatin 130 mg/m\^2 on Day 2 followed by oral dosing of capecitabine 1000 mg/m\^2 twice-daily (BID) from Day 5 to Day 14 . In Cycle 2, participants received IV infusion of oxaliplatin 130 mg//m\^2 over 2 hours on Day 1 along with capecitabine 1000 mg/m\^2 orally BID until Day 14. In Cycle 3, participants received IV infusion of bevacizumab 7.5 mg/kg over 90 minutes on Day 1 at the same time as oxaliplatin 130 mg//m\^2 was administered as an IV infusion over 2 hours (Day 1 every 3 weeks) along with capecitabine1000 mg//m\^2 orally BID until Day 14. Treatment with the Cycle 3 dosing regimen continued for a further 13 cycles (i.e. Cycle 16) or until progressive disease or unacceptable toxicity or until the participant withdrew consent
|
|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
11.1%
4/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
Gastrointestinal disorders
Abdominal pain
|
5.6%
2/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
5.6%
2/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
Gastrointestinal disorders
Enteritis
|
2.8%
1/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
Gastrointestinal disorders
Intestinal obstruction
|
2.8%
1/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
Gastrointestinal disorders
Vomiting
|
2.8%
1/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
Metabolism and nutrition disorders
Dehydration
|
16.7%
6/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
General disorders
Pyrexia
|
8.3%
3/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
General disorders
Pain
|
2.8%
1/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
Blood and lymphatic system disorders
Neutropenia
|
5.6%
2/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
2.8%
1/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
Psychiatric disorders
Anxiety
|
2.8%
1/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
Psychiatric disorders
Depression
|
2.8%
1/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
Injury, poisoning and procedural complications
Hip fracture
|
2.8%
1/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
2.8%
1/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
Other adverse events
| Measure |
Capecitabine+ Oxaliplatin+ Bevacizumab
n=36 participants at risk
In Cycle 1, participants received a single oral dose of capecitabine 1000 milligrams per meter square (mg/m\^2 on Day 1 followed by 2-hour intravenous (IV) infusion of oxaliplatin 130 mg/m\^2 on Day 2 followed by oral dosing of capecitabine 1000 mg/m\^2 twice-daily (BID) from Day 5 to Day 14 . In Cycle 2, participants received IV infusion of oxaliplatin 130 mg//m\^2 over 2 hours on Day 1 along with capecitabine 1000 mg/m\^2 orally BID until Day 14. In Cycle 3, participants received IV infusion of bevacizumab 7.5 mg/kg over 90 minutes on Day 1 at the same time as oxaliplatin 130 mg//m\^2 was administered as an IV infusion over 2 hours (Day 1 every 3 weeks) along with capecitabine1000 mg//m\^2 orally BID until Day 14. Treatment with the Cycle 3 dosing regimen continued for a further 13 cycles (i.e. Cycle 16) or until progressive disease or unacceptable toxicity or until the participant withdrew consent
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Gastrointestinal disorders
Nausea
|
83.3%
30/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
Gastrointestinal disorders
Diarrhoea
|
80.6%
29/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
Gastrointestinal disorders
Vomiting
|
58.3%
21/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
Gastrointestinal disorders
Abdominal pain
|
38.9%
14/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
Gastrointestinal disorders
Constipation
|
27.8%
10/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
Gastrointestinal disorders
Abdominal discomfort
|
19.4%
7/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
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Gastrointestinal disorders
Flatulence
|
16.7%
6/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
Gastrointestinal disorders
Dyspepsia
|
13.9%
5/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
Gastrointestinal disorders
Rectal haemorrhage
|
11.1%
4/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
Gastrointestinal disorders
Stomatitis
|
11.1%
4/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
Gastrointestinal disorders
Abdominal pain upper
|
8.3%
3/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
Gastrointestinal disorders
Haematochezia
|
8.3%
3/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
Gastrointestinal disorders
Toothache
|
8.3%
3/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
Gastrointestinal disorders
Anorectal discomfort
|
5.6%
2/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
Gastrointestinal disorders
Dry mouth
|
5.6%
2/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
Gastrointestinal disorders
Dysphagia
|
5.6%
2/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
Gastrointestinal disorders
Gastrooesophageal reflux Disease
|
5.6%
2/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
Gastrointestinal disorders
Haemorrhoids
|
5.6%
2/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
Gastrointestinal disorders
Rectal Discharge
|
5.6%
2/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
General disorders
Fatigue
|
88.9%
32/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
General disorders
Temperature intolerance
|
27.8%
10/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
General disorders
Mucosal inflammation
|
25.0%
9/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
General disorders
Oedema peripheral
|
19.4%
7/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
General disorders
Pyrexia
|
11.1%
4/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
General disorders
Catheter site erythema
|
8.3%
3/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
General disorders
Chills
|
8.3%
3/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
General disorders
Injection site pain
|
8.3%
3/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
General disorders
Pain
|
8.3%
3/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
General disorders
Catheter related complication
|
5.6%
2/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
General disorders
Catheter site rash
|
5.6%
2/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
General disorders
Chest discomfort
|
5.6%
2/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
General disorders
Injection site discolouration
|
5.6%
2/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
61.1%
22/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
Nervous system disorders
Neuropathy peripheral
|
38.9%
14/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
Nervous system disorders
Headache
|
25.0%
9/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
Nervous system disorders
Paraesthesia
|
16.7%
6/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
Nervous system disorders
Dysgeusia
|
13.9%
5/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
Nervous system disorders
Dizziness
|
11.1%
4/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
Nervous system disorders
Ataxia
|
5.6%
2/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
Nervous system disorders
Neuralgia
|
5.6%
2/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
Skin and subcutaneous tissue disorders
Palmar-plantar
|
55.6%
20/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
Skin and subcutaneous tissue disorders
Erythrodysaesthesia syndrome Dry skin
|
13.9%
5/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
Skin and subcutaneous tissue disorders
Rash
|
13.9%
5/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
Skin and subcutaneous tissue disorders
Skin hyperpigmentation
|
13.9%
5/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
Skin and subcutaneous tissue disorders
Nail disorder
|
8.3%
3/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
Skin and subcutaneous tissue disorders
Dermatitis acneiform
|
5.6%
2/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
5.6%
2/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
25.0%
9/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
16.7%
6/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
16.7%
6/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
11.1%
4/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
Musculoskeletal and connective tissue disorders
Joint stiffness
|
11.1%
4/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
8.3%
3/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
Musculoskeletal and connective tissue disorders
Pain in jaw
|
8.3%
3/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
5.6%
2/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
5.6%
2/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
Musculoskeletal and connective tissue disorders
Trismus
|
5.6%
2/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
Metabolism and nutrition disorders
Anorexia
|
55.6%
20/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
27.8%
10/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
Metabolism and nutrition disorders
Dehydration
|
19.4%
7/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
8.3%
3/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
19.4%
7/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
16.7%
6/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngolaryngeal pain
|
13.9%
5/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
Respiratory, thoracic and mediastinal disorders
Dysphonia
|
11.1%
4/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
11.1%
4/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea exertional
|
11.1%
4/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
Respiratory, thoracic and mediastinal disorders
Hiccups
|
5.6%
2/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
5.6%
2/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
Respiratory, thoracic and mediastinal disorders
Wheezing
|
5.6%
2/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
Psychiatric disorders
Anxiety
|
19.4%
7/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
Psychiatric disorders
Insomnia
|
19.4%
7/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
Psychiatric disorders
Confusional state
|
11.1%
4/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
Psychiatric disorders
Depression
|
8.3%
3/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
Psychiatric disorders
Restlessness
|
5.6%
2/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
Vascular disorders
Thrombosis
|
16.7%
6/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
Vascular disorders
Hypertension
|
13.9%
5/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
Vascular disorders
Flushing
|
8.3%
3/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
Vascular disorders
Hypotension
|
8.3%
3/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
Blood and lymphatic system disorders
Neutropenia
|
30.6%
11/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
Blood and lymphatic system disorders
Anaemia
|
8.3%
3/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
5.6%
2/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
Eye disorders
Lacrimation increased
|
16.7%
6/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
Eye disorders
Vision blurred
|
8.3%
3/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
Investigations
Gamma-glutamyltransferase increased
|
5.6%
2/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
Investigations
Weight decreased
|
5.6%
2/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
Renal and urinary disorders
Dysuria
|
5.6%
2/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
Renal and urinary disorders
Proteinuria
|
5.6%
2/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
Cardiac disorders
Palpitations
|
5.6%
2/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
Cardiac disorders
Tachycardia
|
5.6%
2/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
|
Immune system disorders
Hypersensitivity
|
5.6%
2/36 • Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
Additional Information
Roche Trial Information Hotline
F. Hoffmann-La Roche AG
Phone: +41 616878333
Email: [email protected]
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