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Trial record 32 of 54 for:    colon cancer | ( Map: Mississippi, United States )

A Study Combining FOLFOX or FOLFIRI With AG-013736 or Bevacizumab (Avastin) in Patients With Metastatic Colorectal Cancer After Failure Of One First Line Regimen

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ClinicalTrials.gov Identifier: NCT00615056
Recruitment Status : Completed
First Posted : February 14, 2008
Results First Posted : April 20, 2012
Last Update Posted : April 19, 2013
Sponsor:
Information provided by (Responsible Party):
Pfizer

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Colorectal Neoplasms
Interventions Drug: Bevacizumab (avastin)
Drug: FOLFIRI (Irinotecan, leucovorin, 5-fluorouracil [5FU])
Drug: AG-013736 (axitinib)
Drug: FOLFOX (oxaliplatin, leucovorin, 5-fluorouracil [5FU])
Drug: FOLFIRI (irinotecan, leucovorin, 5-fluorouracil [5FU])
Enrollment 171
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Axitinib + FOLFIRI Bevacizumab + FOLFIRI Axitinib + FOLFOX Bevacizumab + FOLFOX
Hide Arm/Group Description Axitinib (AG-013736) tablet starting dose 5 milligram (mg) orally twice daily (BID) along with combination chemotherapy of irinotecan, 5- flurouracil (5-FU) and leucovorin (LV) (FOLFIRI) regimen consisting of irinotecan 180 mg per square meter (mg/m^2) 90 minutes intravenous (IV) infusion, concurrently with LV 400 mg/m^2 (or levo-leucovarin [l-LV] 200 mg /m^2) 2 hours (hrs) IV infusion followed immediately by 5-FU 400 mg/m^2 IV bolus injection and a subsequent 5-FU 2400 mg/m^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle. Bevacizumab 5mg/kilogram (kg) 30-90 minutes IV infusion (based on tolerance) every 2 weeks along with FOLFIRI regimen consisting of irinotecan 180 mg/m^2 90 minutes IV infusion, concurrently with LV 400 mg/m^2 (or l-LV 200 mg /m^2) 2 hrs IV infusion followed immediately by 5-FU 400 mg/m^2 IV bolus injection and a subsequent 5-FU 2400 mg/m^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle. Axitinib (AG-013736) tablet starting dose 5 mg BID along with combination chemotherapy of oxaliplatin, LV and 5-FU (FOLFOX) regimen consisting of oxaliplatin 85 mg/m^2 120 minutes IV infusion, concurrently with LV 400 mg/m^2 (or l-LV 200 mg /m^2) 2 hrs IV infusion followed immediately by 5-FU 400 mg/m^2 IV bolus injection and a subsequent 5-FU 2400 mg/m^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle. Bevacizumab 5mg/kg 30-90 minutes IV infusion (based on tolerance) every 2 weeks along with FOLFOX regimen consisting of oxaliplatin 85 mg/m^2 120 minutes IV infusion, concurrently with LV 400 mg/m^2 (or l-LV 200 mg /m^2) 2 hrs IV infusion followed immediately by 5-FU 400 mg/m^2 IV bolus injection and a subsequent 5-FU 2400 mg/m^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle.
Period Title: Overall Study
Started 49 51 36 35
Treated 46 51 36 35
Completed 0 0 0 0
Not Completed 49 51 36 35
Reason Not Completed
Death             31             31             21             23
Lost to Follow-up             1             2             4             5
Other             13             15             10             7
Objective progression or relapse             0             2             0             0
Withdrawal by Subject             0             1             1             0
Discontinued by Sponsor             1             0             0             0
Randomized but not treated             3             0             0             0
Arm/Group Title Axitinib + FOLFIRI Bevacizumab + FOLFIRI Axitinib + FOLFOX Bevacizumab + FOLFOX Total
Hide Arm/Group Description Axitinib (AG-013736) tablet starting dose 5 milligram (mg) orally twice daily (BID) along with combination chemotherapy of irinotecan, 5- flurouracil (5-FU) and leucovorin (LV) (FOLFIRI) regimen consisting of irinotecan 180 mg per square meter (mg/m^2) 90 minutes intravenous (IV) infusion, concurrently with LV 400 mg/m^2 (or levo-leucovarin [l-LV] 200 mg /m^2) 2 hours (hrs) IV infusion followed immediately by 5-FU 400 mg/m^2 IV bolus injection and a subsequent 5-FU 2400 mg/m^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle. Bevacizumab 5mg/kilogram (kg) 30-90 minutes IV infusion (based on tolerance) every 2 weeks along with FOLFIRI regimen consisting of irinotecan 180 mg/m^2 90 minutes IV infusion, concurrently with LV 400 mg/m^2 (or l-LV 200 mg /m^2) 2 hrs IV infusion followed immediately by 5-FU 400 mg/m^2 IV bolus injection and a subsequent 5-FU 2400 mg/m^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle. Axitinib (AG-013736) tablet starting dose 5 mg BID along with combination chemotherapy of oxaliplatin, LV and 5-FU (FOLFOX) regimen consisting of oxaliplatin 85 mg/m^2 120 minutes IV infusion, concurrently with LV 400 mg/m^2 (or l-LV 200 mg /m^2) 2 hrs IV infusion followed immediately by 5-FU 400 mg/m^2 IV bolus injection and a subsequent 5-FU 2400 mg/m^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle. Bevacizumab 5mg/kg 30-90 minutes IV infusion (based on tolerance) every 2 weeks along with FOLFOX regimen consisting of oxaliplatin 85 mg/m^2 120 minutes IV infusion, concurrently with LV 400 mg/m^2 (or l-LV 200 mg /m^2) 2 hrs IV infusion followed immediately by 5-FU 400 mg/m^2 IV bolus injection and a subsequent 5-FU 2400 mg/m^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle. Total of all reporting groups
Overall Number of Baseline Participants 49 51 36 35 171
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 49 participants 51 participants 36 participants 35 participants 171 participants
18 to 44 years 5 6 3 1 15
45 to 64 years 30 34 21 22 107
Greater than and equal to 65 years 14 11 12 12 49
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 49 participants 51 participants 36 participants 35 participants 171 participants
Female
18
  36.7%
24
  47.1%
20
  55.6%
11
  31.4%
73
  42.7%
Male
31
  63.3%
27
  52.9%
16
  44.4%
24
  68.6%
98
  57.3%
1.Primary Outcome
Title Progression Free Survival (PFS)
Hide Description Time in months from start of study treatment to first documentation of objective tumor progression or death due to any cause. PFS was calculated as (first event date minus the date of first dose of study medication plus 1) divided by 30.4. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease [PD]), or from adverse event (AE) data (where the outcome was "Death").
Time Frame Baseline until disease progression or discontinuation from the study due to any cause, assessed every 8 week up to 130 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) population included all participants who were randomized, with study drug assignment designated according to initial randomization, regardless of whether participants received study drug, or receive a different drug from that to which they were randomized.
Arm/Group Title Axitinib + FOLFIRI Bevacizumab + FOLFIRI Axitinib + FOLFOX Bevacizumab + FOLFOX
Hide Arm/Group Description:
Axitinib (AG-013736) tablet starting dose 5 milligram (mg) orally twice daily (BID) along with combination chemotherapy of irinotecan, 5- flurouracil (5-FU) and leucovorin (LV) (FOLFIRI) regimen consisting of irinotecan 180 mg per square meter (mg/m^2) 90 minutes intravenous (IV) infusion, concurrently with LV 400 mg/m^2 (or levo-leucovarin [l-LV] 200 mg /m^2) 2 hours (hrs) IV infusion followed immediately by 5-FU 400 mg/m^2 IV bolus injection and a subsequent 5-FU 2400 mg/m^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle.
Bevacizumab 5mg/kilogram (kg) 30-90 minutes IV infusion (based on tolerance) every 2 weeks along with FOLFIRI regimen consisting of irinotecan 180 mg/m^2 90 minutes IV infusion, concurrently with LV 400 mg/m^2 (or l-LV 200 mg /m^2) 2 hrs IV infusion followed immediately by 5-FU 400 mg/m^2 IV bolus injection and a subsequent 5-FU 2400 mg/m^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle.
Axitinib (AG-013736) tablet starting dose 5 mg BID along with combination chemotherapy of oxaliplatin, LV and 5-FU (FOLFOX) regimen consisting of oxaliplatin 85 mg/m^2 120 minutes IV infusion, concurrently with LV 400 mg/m^2 (or l-LV 200 mg /m^2) 2 hrs IV infusion followed immediately by 5-FU 400 mg/m^2 IV bolus injection and a subsequent 5-FU 2400 mg/m^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle.
Bevacizumab 5mg/kg 30-90 minutes IV infusion (based on tolerance) every 2 weeks along with FOLFOX regimen consisting of oxaliplatin 85 mg/m^2 120 minutes IV infusion, concurrently with LV 400 mg/m^2 (or l-LV 200 mg /m^2) 2 hrs IV infusion followed immediately by 5-FU 400 mg/m^2 IV bolus injection and a subsequent 5-FU 2400 mg/m^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle.
Overall Number of Participants Analyzed 49 51 36 35
Median (95% Confidence Interval)
Unit of Measure: Months
5.72
(4.50 to 7.42)
6.87
(4.96 to 9.13)
7.59
(5.62 to 11.07)
6.44
(5.52 to 13.11)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Axitinib + FOLFIRI, Bevacizumab + FOLFIRI
Comments Differences in PFS between treatment arms was analyzed by 1-sided log rank test, stratified for Eastern Cooperative Oncology Group (ECOG) performance status (0 versus 1) and prior treatment with bevacizumab (yes versus no).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8268
Comments One-sided log-rank test at alpha = 0.15 significance level was used.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.273
Confidence Interval (2-Sided) 95%
0.769 to 2.108
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Axitinib + FOLFOX, Bevacizumab + FOLFOX
Comments Differences in PFS between treatment arms was analyzed by 1-sided log rank test, stratified for ECOG performance status (0 versus 1) and prior treatment with bevacizumab (yes versus no).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5498
Comments One-sided log-rank test at alpha = 0.15 significance level was used.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.041
Confidence Interval (2-Sided) 95%
0.553 to 1.041
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Overall Survival (OS)
Hide Description Time in months from the start of study treatment to date of death due to any cause. OS was calculated as (the death date minus the date of first dose of study medication plus 1) divided by 30.4. Death was determined from adverse event data (where outcome was death) or from follow-up contact data (where the participant current status was death).
Time Frame Baseline until death or up to 1 year after the randomization of last participant
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants who were randomized, with study drug assignment designated according to initial randomization, regardless of whether participants received study drug, or receive a different drug from that to which they were randomized.
Arm/Group Title Axitinib + FOLFIRI Bevacizumab + FOLFIRI Axitinib + FOLFOX Bevacizumab + FOLFOX
Hide Arm/Group Description:
Axitinib (AG-013736) tablet starting dose 5 milligram (mg) orally twice daily (BID) along with combination chemotherapy of irinotecan, 5- flurouracil (5-FU) and leucovorin (LV) (FOLFIRI) regimen consisting of irinotecan 180 mg per square meter (mg/m^2) 90 minutes intravenous (IV) infusion, concurrently with LV 400 mg/m^2 (or levo-leucovarin [l-LV] 200 mg /m^2) 2 hours (hrs) IV infusion followed immediately by 5-FU 400 mg/m^2 IV bolus injection and a subsequent 5-FU 2400 mg/m^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle.
Bevacizumab 5mg/kilogram (kg) 30-90 minutes IV infusion (based on tolerance) every 2 weeks along with FOLFIRI regimen consisting of irinotecan 180 mg/m^2 90 minutes IV infusion, concurrently with LV 400 mg/m^2 (or l-LV 200 mg /m^2) 2 hrs IV infusion followed immediately by 5-FU 400 mg/m^2 IV bolus injection and a subsequent 5-FU 2400 mg/m^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle.
Axitinib (AG-013736) tablet starting dose 5 mg BID along with combination chemotherapy of oxaliplatin, LV and 5-FU (FOLFOX) regimen consisting of oxaliplatin 85 mg/m^2 120 minutes IV infusion, concurrently with LV 400 mg/m^2 (or l-LV 200 mg /m^2) 2 hrs IV infusion followed immediately by 5-FU 400 mg/m^2 IV bolus injection and a subsequent 5-FU 2400 mg/m^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle.
Bevacizumab 5mg/kg 30-90 minutes IV infusion (based on tolerance) every 2 weeks along with FOLFOX regimen consisting of oxaliplatin 85 mg/m^2 120 minutes IV infusion, concurrently with LV 400 mg/m^2 (or l-LV 200 mg /m^2) 2 hrs IV infusion followed immediately by 5-FU 400 mg/m^2 IV bolus injection and a subsequent 5-FU 2400 mg/m^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle.
Overall Number of Participants Analyzed 49 51 36 35
Median (95% Confidence Interval)
Unit of Measure: Months
12.9
(10.2 to 16.6)
15.7
(12.1 to 23.0)
17.1
(10.1 to 23.0)
14.1
(9.0 to 16.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Axitinib + FOLFIRI, Bevacizumab + FOLFIRI
Comments Differences in OS between treatment arms was analyzed by 1-sided log rank test, stratified for ECOG performance status (0 versus 1) and prior treatment with bevacizumab (yes versus no).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8828
Comments One-sided log-rank test at alpha = 0.15 significance level was used.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.355
Confidence Interval (2-Sided) 95%
0.820 to 2.238
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Axitinib + FOLFOX, Bevacizumab + FOLFOX
Comments Differences in OS between treatment arms was analyzed by 1-sided log rank test, stratified for ECOG performance status (0 versus 1) and prior treatment with bevacizumab (yes versus no).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1159
Comments One-sided log-rank test at alpha = 0.15 significance level was used.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.689
Confidence Interval (2-Sided) 95%
0.373 to 1.273
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Percentage of Participants With Objective Response (OR)
Hide Description Percentage of participants with objective response based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). CR are those that persist on repeat imaging study at least 4 weeks after initial documentation of response. PR are those with at least 30 percent decrease in sum of the longest dimensions of target lesions taking as a reference the baseline sum longest dimensions, with non target lesions not increased or absent.
Time Frame Baseline until disease progression or discontinuation from the study due to any cause, assessed every 8 weeks up to 130 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants who were randomized, with study drug assignment designated according to initial randomization, regardless of whether participants received study drug, or receive a different drug from that to which they were randomized.
Arm/Group Title Axitinib + FOLFIRI Bevacizumab + FOLFIRI Axitinib + FOLFOX Bevacizumab + FOLFOX
Hide Arm/Group Description:
Axitinib (AG-013736) tablet starting dose 5 milligram (mg) orally twice daily (BID) along with combination chemotherapy of irinotecan, 5- flurouracil (5-FU) and leucovorin (LV) (FOLFIRI) regimen consisting of irinotecan 180 mg per square meter (mg/m^2) 90 minutes intravenous (IV) infusion, concurrently with LV 400 mg/m^2 (or levo-leucovarin [l-LV] 200 mg /m^2) 2 hours (hrs) IV infusion followed immediately by 5-FU 400 mg/m^2 IV bolus injection and a subsequent 5-FU 2400 mg/m^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle.
Bevacizumab 5mg/kilogram (kg) 30-90 minutes IV infusion (based on tolerance) every 2 weeks along with FOLFIRI regimen consisting of irinotecan 180 mg/m^2 90 minutes IV infusion, concurrently with LV 400 mg/m^2 (or l-LV 200 mg /m^2) 2 hrs IV infusion followed immediately by 5-FU 400 mg/m^2 IV bolus injection and a subsequent 5-FU 2400 mg/m^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle.
Axitinib (AG-013736) tablet starting dose 5 mg BID along with combination chemotherapy of oxaliplatin, LV and 5-FU (FOLFOX) regimen consisting of oxaliplatin 85 mg/m^2 120 minutes IV infusion, concurrently with LV 400 mg/m^2 (or l-LV 200 mg /m^2) 2 hrs IV infusion followed immediately by 5-FU 400 mg/m^2 IV bolus injection and a subsequent 5-FU 2400 mg/m^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle.
Bevacizumab 5mg/kg 30-90 minutes IV infusion (based on tolerance) every 2 weeks along with FOLFOX regimen consisting of oxaliplatin 85 mg/m^2 120 minutes IV infusion, concurrently with LV 400 mg/m^2 (or l-LV 200 mg /m^2) 2 hrs IV infusion followed immediately by 5-FU 400 mg/m^2 IV bolus injection and a subsequent 5-FU 2400 mg/m^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle.
Overall Number of Participants Analyzed 49 51 36 35
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
24.5
(13.3 to 38.9)
23.5
(12.8 to 37.5)
19.4
(8.2 to 36.0)
20.0
(8.4 to 36.9)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Axitinib + FOLFIRI, Bevacizumab + FOLFIRI
Comments One-sided Pearson chi square test at alpha = 0.15 significance level was used.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4552
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1
Confidence Interval (2-Sided) 95%
-15.8 to 17.7
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Axitinib + FOLFOX, Bevacizumab + FOLFOX
Comments One-sided Pearson chi square test at alpha = 0.15 significance level was used.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5235
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.6
Confidence Interval (2-Sided) 95%
-19.1 to 18.0
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Duration of Response (DR)
Time Frame Baseline until disease progression or discontinuation from the study due to any cause, assessed every 8 weeks up to 130 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
DR was calculated for the subgroup of participants from the ITT set, with a confirmed objective tumor response (CR or PR).
Arm/Group Title Axitinib + FOLFIRI Bevacizumab + FOLFIRI Axitinib + FOLFOX Bevacizumab + FOLFOX
Hide Arm/Group Description:
Axitinib (AG-013736) tablet starting dose 5 milligram (mg) orally twice daily (BID) along with combination chemotherapy of irinotecan, 5- flurouracil (5-FU) and leucovorin (LV) (FOLFIRI) regimen consisting of irinotecan 180 mg per square meter (mg/m^2) 90 minutes intravenous (IV) infusion, concurrently with LV 400 mg/m^2 (or levo-leucovarin [l-LV] 200 mg /m^2) 2 hours (hrs) IV infusion followed immediately by 5-FU 400 mg/m^2 IV bolus injection and a subsequent 5-FU 2400 mg/m^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle.
Bevacizumab 5mg/kilogram (kg) 30-90 minutes IV infusion (based on tolerance) every 2 weeks along with FOLFIRI regimen consisting of irinotecan 180 mg/m^2 90 minutes IV infusion, concurrently with LV 400 mg/m^2 (or l-LV 200 mg /m^2) 2 hrs IV infusion followed immediately by 5-FU 400 mg/m^2 IV bolus injection and a subsequent 5-FU 2400 mg/m^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle.
Axitinib (AG-013736) tablet starting dose 5 mg BID along with combination chemotherapy of oxaliplatin, LV and 5-FU (FOLFOX) regimen consisting of oxaliplatin 85 mg/m^2 120 minutes IV infusion, concurrently with LV 400 mg/m^2 (or l-LV 200 mg /m^2) 2 hrs IV infusion followed immediately by 5-FU 400 mg/m^2 IV bolus injection and a subsequent 5-FU 2400 mg/m^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle.
Bevacizumab 5mg/kg 30-90 minutes IV infusion (based on tolerance) every 2 weeks along with FOLFOX regimen consisting of oxaliplatin 85 mg/m^2 120 minutes IV infusion, concurrently with LV 400 mg/m^2 (or l-LV 200 mg /m^2) 2 hrs IV infusion followed immediately by 5-FU 400 mg/m^2 IV bolus injection and a subsequent 5-FU 2400 mg/m^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle.
Overall Number of Participants Analyzed 12 12 7 7
Median (95% Confidence Interval)
Unit of Measure: Months
7.52 [1] 
(5.22 to NA)
12.29
(7.39 to 12.84)
10.15
(4.17 to 12.91)
10.94
(4.53 to 12.68)
[1]
Upper limit of confidence interval was not estimable due to the large number of participants censored.
5.Secondary Outcome
Title Change From Baseline in MD Anderson Symptoms Inventory Diarrhea (MDASI–D) Symptom Severity Score at Day 1 of Cycles 2-5, Day 1 of Every Odd-numbered Cycle Throughout the Study and End of Treatment (Cycle 65) or Withdrawal
Hide Description Symptom severity score is comprised of average of 14 MDASI-D core items (pain, fatigue, nausea, disturbed sleep, distress, shortness of breath, remembering things, lack of appetite, drowsiness, dry mouth, sadness, vomiting, numbness or tingling and diarrhea) and ranges from 0 to 10. Participants were asked to rate severity of each symptom at their worst in last week; each item rated from 0 to 10, with 0 = symptom not present and 10 = as bad as you can imagine. Lower scores indicated better outcome. Total average score range: 0 to 10.
Time Frame Baseline, Day 1 of cycles 2- 5, Day 1 of every odd-numbered cycle throughout the study and end of treatment (cycle 65) or withdrawal
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. Here 'N’ (number of participants analyzed) signifies participants evaluable for this measure and ‘n’ is number of participants analyzed at specific time point for each treatment arm respectively.
Arm/Group Title Axitinib + FOLFIRI Bevacizumab + FOLFIRI Axitinib + FOLFOX Bevacizumab + FOLFOX
Hide Arm/Group Description:
Axitinib (AG-013736) tablet starting dose 5 milligram (mg) orally twice daily (BID) along with combination chemotherapy of irinotecan, 5- flurouracil (5-FU) and leucovorin (LV) (FOLFIRI) regimen consisting of irinotecan 180 mg per square meter (mg/m^2) 90 minutes intravenous (IV) infusion, concurrently with LV 400 mg/m^2 (or levo-leucovarin [l-LV] 200 mg /m^2) 2 hours (hrs) IV infusion followed immediately by 5-FU 400 mg/m^2 IV bolus injection and a subsequent 5-FU 2400 mg/m^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle.
Bevacizumab 5mg/kilogram (kg) 30-90 minutes IV infusion (based on tolerance) every 2 weeks along with FOLFIRI regimen consisting of irinotecan 180 mg/m^2 90 minutes IV infusion, concurrently with LV 400 mg/m^2 (or l-LV 200 mg /m^2) 2 hrs IV infusion followed immediately by 5-FU 400 mg/m^2 IV bolus injection and a subsequent 5-FU 2400 mg/m^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle.
Axitinib (AG-013736) tablet starting dose 5 mg BID along with combination chemotherapy of oxaliplatin, LV and 5-FU (FOLFOX) regimen consisting of oxaliplatin 85 mg/m^2 120 minutes IV infusion, concurrently with LV 400 mg/m^2 (or l-LV 200 mg /m^2) 2 hrs IV infusion followed immediately by 5-FU 400 mg/m^2 IV bolus injection and a subsequent 5-FU 2400 mg/m^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle.
Bevacizumab 5mg/kg 30-90 minutes IV infusion (based on tolerance) every 2 weeks along with FOLFOX regimen consisting of oxaliplatin 85 mg/m^2 120 minutes IV infusion, concurrently with LV 400 mg/m^2 (or l-LV 200 mg /m^2) 2 hrs IV infusion followed immediately by 5-FU 400 mg/m^2 IV bolus injection and a subsequent 5-FU 2400 mg/m^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle.
Overall Number of Participants Analyzed 39 46 35 33
Mean (95% Confidence Interval)
Unit of Measure: Units on a Scale
Baseline (n=39,46,35,33)
2.1
(1.6 to 2.6)
1.8
(1.3 to 2.2)
1.9
(1.3 to 2.5)
2.0
(1.4 to 2.7)
Change at Cycle 2/Day 1 (n=35, 39, 34,28)
0.6
(0.2 to 1.1)
0.5
(-0.1 to 1.0)
0.7
(0.2 to 1.2)
0.0
(-0.4 to 0.5)
Change at Cycle 3/Day 1 (n=36,36,33,26)
0.8
(0.2 to 1.4)
0.2
(-0.3 to 0.6)
0.3
(-0.4 to 1.0)
0.2
(-0.3 to 0.7)
Change at Cycle 4/Day 1 (n=29,37,32,25)
0.8
(0.0 to 1.5)
0.0
(-0.4 to 0.5)
0.5
(-0.2 to 1.1)
0.5
(-0.1 to 1.1)
Change at Cycle 5/Day 1 (n=28,29,24,24)
0.5
(0.0 to 1.1)
0.1
(-0.4 to 0.7)
0.9
(0.2 to 1.7)
0.4
(-0.2 to 0.9)
Change at Cycle 7/Day 1 (n=26,31,22,20)
0.7
(0.1 to 1.2)
0.0
(-0.6 to 0.5)
0.6
(0.1 to 1.1)
0.2
(-0.5 to 0.9)
Change at Cycle 9/Day 1 (n=19,26,19,17)
1.1
(0.3 to 1.9)
-0.2
(-0.7 to 0.2)
0.6
(-0.1 to 1.3)
0.8
(0.3 to 1.3)
Change at Cycle 11/Day 1 (n=15,24,16,15)
1.0
(0.1 to 1.9)
0.1
(-0.5 to 0.7)
1.0
(0.2 to 1.8)
0.1
(-0.8 to 1.1)
Change at Cycle 13/Day 1 (n=13,19,15,10)
1.0
(-0.5 to 2.6)
0.1
(-0.6 to 0.7)
0.9
(0.2 to 1.6)
0.8
(0.1 to 1.4)
Change at Cycle 15/Day 1 (n=7,17,12,8)
0.8
(-1.6 to 3.3)
0.2
(-0.3 to 0.7)
0.5
(-0.4 to 1.3)
1.0
(0.4 to 1.6)
Change at Cycle 17/Day 1 (n=6,11,11,7)
2.0
(-0.9 to 5.0)
0.4
(-0.3 to 1.0)
0.9
(0.1 to 1.8)
1.7
(0.7 to 2.7)
Change at Cycle 19/Day 1 (n=6,10,9,5)
1.3
(-1.5 to 4.1)
0.5
(-0.7 to 1.7)
0.8
(-0.2 to 1.8)
1.4
(0.7 to 2.2)
Change at Cycle 21/Day 1 (n=6,9,7,4)
1.1
(-2.2 to 4.4)
0.5
(-0.5 to 1.5)
0.9
(-0.9 to 2.7)
1.6
(0.3 to 2.8)
Change at Cycle 23/Day 1 (n=5,7,6,4)
2.6
(0.3 to 4.8)
-0.3
(-0.9 to 0.3)
0.4
(-1.4 to 2.3)
1.0
(0.8 to 1.2)
Change at Cycle 25/Day 1 (n=5,7,6,3)
2.2
(-1.2 to 5.6)
0.1
(-1.2 to 1.4)
0.2
(-2.0 to 2.3)
1.0
(0.5 to 1.4)
Change at Cycle 27/Day 1 (n=2,7,3,3)
2.3
(-20.8 to 25.5)
0.4
(-1.4 to 2.3)
0.3
(-5.4 to 5.9)
1.1
(0.6 to 1.5)
Change at Cycle 29/Day 1 (n=2,5,2,3)
2.8
(-25.8 to 31.4)
-0.2
(-1.3 to 0.9)
-0.8
(-1.7 to 0.1)
0.9
(-0.3 to 2.1)
Change at Cycle 31/Day 1 (n=1,5,2,2)
4.9 [1] 
(NA to NA)
-0.4
(-1.2 to 0.3)
-0.3
(-5.7 to 5.2)
0.9
(-1.4 to 3.2)
Change at Cycle 33/Day 1 (n=1,3,2,1)
5.0 [1] 
(NA to NA)
-0.6
(-3.2 to 2.0)
-0.8
(-7.6 to 6.1)
0.5 [1] 
(NA to NA)
Change at Cycle 35/Day 1 (n=0,4,1,1)
NA [2] 
(NA to NA)
-0.4
(-1.5 to 0.7)
0.4 [1] 
(NA to NA)
2.4 [1] 
(NA to NA)
Change at Cycle 37/Day 1 (n=0,4,0,1)
NA [2] 
(NA to NA)
-0.5
(-1.3 to 0.4)
NA [2] 
(NA to NA)
1.0 [1] 
(NA to NA)
Change at Cycle 39/Day 1 (n=0,2,0,1)
NA [2] 
(NA to NA)
-0.4
(-0.8 to 0.1)
NA [2] 
(NA to NA)
1.0 [1] 
(NA to NA)
Change at Cycle 41/Day 1 (n=0,2,0,1)
NA [2] 
(NA to NA)
-0.3
(-0.8 to 0.1)
NA [2] 
(NA to NA)
1.4 [1] 
(NA to NA)
Change at Cycle 43/Day 1 (n=0,1,0,1)
NA [2] 
(NA to NA)
-0.4 [1] 
(NA to NA)
NA [2] 
(NA to NA)
2.0 [1] 
(NA to NA)
Change at Cycle 45/Day 1 (n=0,0,0,1 )
NA [2] 
(NA to NA)
NA [2] 
(NA to NA)
NA [2] 
(NA to NA)
2.2 [1] 
(NA to NA)
Change at Cycle 47/Day 1 (n=0,1,0,0)
NA [2] 
(NA to NA)
-0.4 [1] 
(NA to NA)
NA [2] 
(NA to NA)
NA [2] 
(NA to NA)
Change at Cycle 49/Day 1 (n=0,1,0,0)
NA [2] 
(NA to NA)
-0.5 [1] 
(NA to NA)
NA [2] 
(NA to NA)
NA [2] 
(NA to NA)
Change at Cycle 51/Day 1 (n=0,1,0,0)
NA [2] 
(NA to NA)
-0.4 [1] 
(NA to NA)
NA [2] 
(NA to NA)
NA [2] 
(NA to NA)
Change at Cycle 53/Day 1 (n=0,1,0,0)
NA [2] 
(NA to NA)
-0.4 [1] 
(NA to NA)
NA [2] 
(NA to NA)
NA [2] 
(NA to NA)
Change at Cycle 55/Day 1 (n=0,1,0,0)
NA [2] 
(NA to NA)
-0.3 [1] 
(NA to NA)
NA [2] 
(NA to NA)
NA [2] 
(NA to NA)
Change at Cycle 57/Day 1 (n=0,1,0,0)
NA [2] 
(NA to NA)
-0.3 [1] 
(NA to NA)
NA [2] 
(NA to NA)
NA [2] 
(NA to NA)
Change at Cycle 59/Day 1 (n=0,1,0,0)
NA [2] 
(NA to NA)
-0.3 [1] 
(NA to NA)
NA [2] 
(NA to NA)
NA [2] 
(NA to NA)
Change at Cycle 61/Day 1 (n=0,1,0,0)
NA [2] 
(NA to NA)
-0.2 [1] 
(NA to NA)
NA [2] 
(NA to NA)
NA [2] 
(NA to NA)
Change at Cycle 63/Day 1 (n=0,0,0,0)
NA [2] 
(NA to NA)
NA [2] 
(NA to NA)
NA [2] 
(NA to NA)
NA [2] 
(NA to NA)
Change at Cycle 65/Day 1 (n=0,1,0,0)
NA [2] 
(NA to NA)
-0.4 [1] 
(NA to NA)
NA [2] 
(NA to NA)
NA [2] 
(NA to NA)
Change at end of treatment (n=21,29,27,22)
0.7
(-0.2 to 1.6)
0.5
(-0.1 to 1.0)
1.3
(0.4 to 2.1)
0.9
(0.1 to 1.7)
[1]
95% confidence interval was not estimable since only one participant was evaluable.
[2]
Data was not analyzed as no participants were evaluable for the particular cycle.
6.Secondary Outcome
Title Change From Baseline in MDASI–D Symptom Interference Score at Day 1 of Cycles 2-5, Day 1 of Every Odd-numbered Cycle Throughout the Study and End of Treatment (Cycle 65) or Withdrawal
Hide Description Symptom Interference score is comprised of the average of 6 items on feeling or function from the MDASI-D core (general activity, mood, work, relations with others, walking, and enjoyment of life) and ranges from 0 to 10. Participants were asked to rate how much symptoms have interfered in last week; each item rated from 0 to 10, with 0 = did not interfere and 10 = interfered completely. Lower scores indicated better outcome. Total average score range: 0 to 10.
Time Frame Baseline, Day 1 of cycle 2-5, Day 1 of every odd-numbered cycle throughout the study and end of treatment (cycle 65) or withdrawal
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. Here 'N’ (number of participants analyzed) signifies participants evaluable for this measure and ‘n’ is number of participants analyzed at specific time point for each treatment arm respectively.
Arm/Group Title Axitinib + FOLFIRI Bevacizumab + FOLFIRI Axitinib + FOLFOX Bevacizumab + FOLFOX
Hide Arm/Group Description:
Axitinib (AG-013736) tablet starting dose 5 milligram (mg) orally twice daily (BID) along with combination chemotherapy of irinotecan, 5- flurouracil (5-FU) and leucovorin (LV) (FOLFIRI) regimen consisting of irinotecan 180 mg per square meter (mg/m^2) 90 minutes intravenous (IV) infusion, concurrently with LV 400 mg/m^2 (or levo-leucovarin [l-LV] 200 mg /m^2) 2 hours (hrs) IV infusion followed immediately by 5-FU 400 mg/m^2 IV bolus injection and a subsequent 5-FU 2400 mg/m^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle.
Bevacizumab 5mg/kilogram (kg) 30-90 minutes IV infusion (based on tolerance) every 2 weeks along with FOLFIRI regimen consisting of irinotecan 180 mg/m^2 90 minutes IV infusion, concurrently with LV 400 mg/m^2 (or l-LV 200 mg /m^2) 2 hrs IV infusion followed immediately by 5-FU 400 mg/m^2 IV bolus injection and a subsequent 5-FU 2400 mg/m^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle.
Axitinib (AG-013736) tablet starting dose 5 mg BID along with combination chemotherapy of oxaliplatin, LV and 5-FU (FOLFOX) regimen consisting of oxaliplatin 85 mg/m^2 120 minutes IV infusion, concurrently with LV 400 mg/m^2 (or l-LV 200 mg /m^2) 2 hrs IV infusion followed immediately by 5-FU 400 mg/m^2 IV bolus injection and a subsequent 5-FU 2400 mg/m^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle.
Bevacizumab 5mg/kg 30-90 minutes IV infusion (based on tolerance) every 2 weeks along with FOLFOX regimen consisting of oxaliplatin 85 mg/m^2 120 minutes IV infusion, concurrently with LV 400 mg/m^2 (or l-LV 200 mg /m^2) 2 hrs IV infusion followed immediately by 5-FU 400 mg/m^2 IV bolus injection and a subsequent 5-FU 2400 mg/m^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle.
Overall Number of Participants Analyzed 39 46 35 33
Mean (95% Confidence Interval)
Unit of Measure: Units on a Scale
Baseline (n=39,46,35,33)
2.1
(1.4 to 2.8)
1.7
(1.1 to 2.3)
2.4
(1.6 to 3.2)
2.8
(1.8 to 3.9)
Change at Cycle 2/Day 1 (n=35, 39, 34, 28)
0.8
(0.0 to 1.5)
0.9
(0.2 to 1.6)
0.1
(-0.6 to 0.7)
-0.5
(-1.2 to 0.1)
Change at Cycle 3/Day 1 (n=36,36,33,26)
1.3
(0.5 to 2.2)
0.3
(-0.3 to 0.8)
0.3
(-0.6 to 1.2)
-0.2
(-1.0 to 0.6)
Change at Cycle 4/Day 1 (n=29,37,32,25)
0.8
(-0.1 to 1.7)
-0.2
(-0.9 to 0.4)
0.2
(-0.6 to 1.1)
0.5
(-0.2 to 1.3)
Change at Cycle 5/Day 1 (n=28,29,24,24)
1.0
(0.3 to 1.6)
0.4
(-0.7 to 1.4)
0.8
(-0.4 to 2.0)
0.3
(-0.6 to 1.2)
Change at Cycle 7/Day 1 (n=26,30,22,20)
0.7
(-0.1 to 1.5)
0.4
(-0.4 to 1.2)
0.4
(-0.3 to 1.1)
0.0
(-0.8 to 0.7)
Change at Cycle 9/Day 1 (n=18,25,19,17)
1.1
(0.2 to 1.9)
0.3
(-0.6 to 1.1)
0.6
(-0.5 to 1.6)
0.3
(-0.8 to 1.4)
Change at Cycle 11/Day 1 (n=15,24,16,15)
1.0
(0.0 to 2.1)
0.3
(-0.6 to 1.3)
0.8
(0.0 to 1.6)
-0.2
(-1.6 to 1.2)
Change at Cycle 13/Day 1 (n=13,19,15,10)
1.1
(-0.4 to 2.7)
0.7
(-0.2 to 1.5)
1.3
(0.4 to 2.2)
0.7
(-0.7 to 2.1)
Change at Cycle 15/Day 1 (n=7,17,12,8)
2.3
(0.8 to 3.8)
0.9
(-0.3 to 2.0)
-0.1
(-1.4 to 1.3)
1.3
(0.0 to 2.5)
Change at Cycle 17/Day 1 (n=6,11,11,7)
2.4
(0.9 to 3.8)
0.7
(-0.7 to 2.1)
0.7
(-1.3 to 2.6)
2.1
(-0.1 to 4.3)
Change at Cycle 19/Day 1 (n=6,10,9,5)
2.1
(0.6 to 3.6)
0.8
(-0.6 to 2.3)
0.3
(-1.6 to 2.2)
2.4
(1.2 to 3.7)
Change at Cycle 21/Day 1 (n=6,9,7,4)
1.7
(-0.3 to 3.7)
1.0
(-1.2 to 3.2)
0.4
(-1.0 to 1.8)
2.1
(0.8 to 3.4)
Change at Cycle 23/Day 1 (n=5,7,6,4)
2.2
(0.0 to 4.4)
-0.3
(-1.3 to 0.8)
0.9
(-1.7 to 3.4)
1.4
(0.8 to 2.0)
Change at Cycle 25/Day 1 (n=5,7,6,3)
1.6
(-0.9 to 4.1)
0.5
(-2.0 to 3.0)
-0.6
(-2.7 to 1.5)
1.4
(0.5 to 2.3)
Change at Cycle 27/Day 1 (n=2,7,3,3)
1.6
(-16.4 to 19.6)
0.9
(-2.1 to 4.0)
-1.6
(-5.7 to 2.4)
1.3
(0.9 to 1.7)
Change at Cycle 29/Day 1 (n=2,5,2,3)
3.2
(-26.5 to 32.8)
0.0
(-2.3 to 2.2)
-1.3
(-15.0 to 12.5)
1.3
(-0.4 to 3.0)
Change at Cycle 31/Day 1 (n=1,5,2,2)
4.5 [1] 
(NA to NA)
-0.5
(-2.1 to 1.0)
-0.1
(-26.6 to 26.4)
1.2
(-3.1 to 5.4)
Change at Cycle 33/Day 1 (n=1,3,2,1)
4.5 [1] 
(NA to NA)
-0.2
(-4.4 to 3.9)
-0.8
(-29.3 to 27.8)
0.3 [1] 
(NA to NA)
Change at Cycle 35/Day 1 (n=0,4,1,1 )
NA [2] 
(NA to NA)
-0.3
(-1.9 to 1.2)
-1.2 [1] 
(NA to NA)
3.3 [1] 
(NA to NA)
Change at Cycle 37/Day 1 (n=0,4,0,1)
NA [2] 
(NA to NA)
-0.4
(-2.1 to 1.2)
NA [2] 
(NA to NA)
1.3 [1] 
(NA to NA)
Change at Cycle 39/Day 1 (n=0,2,0,1)
NA [2] 
(NA to NA)
-0.3
(-0.3 to -0.3)
NA [2] 
(NA to NA)
2.0 [1] 
(NA to NA)
Change at Cycle 41/Day 1 (n=0,2,0,1)
NA [2] 
(NA to NA)
-0.2
(-2.3 to 2.0)
NA [2] 
(NA to NA)
1.5 [1] 
(NA to NA)
Change at Cycle 43/Day 1 (n=0,1,0,1)
NA [2] 
(NA to NA)
-0.3 [1] 
(NA to NA)
NA [2] 
(NA to NA)
1.8 [1] 
(NA to NA)
Change at Cycle 45/Day 1 (n=0,0,0,1 )
NA [2] 
(NA to NA)
NA [2] 
(NA to NA)
NA [2] 
(NA to NA)
2.5 [1] 
(NA to NA)
Change at Cycle 47/Day 1 (n=0,1,0,0)
NA [2] 
(NA to NA)
-0.2 [1] 
(NA to NA)
NA [2] 
(NA to NA)
NA [2] 
(NA to NA)
Change at Cycle 49/Day 1 (n=0,1,0,0)
NA [2] 
(NA to NA)
-0.3 [1] 
(NA to NA)
NA [2] 
(NA to NA)
NA [2] 
(NA to NA)
Change at Cycle 51/Day 1 (n=0,1,0,0)
NA [2] 
(NA to NA)
-0.3 [1] 
(NA to NA)
NA [2] 
(NA to NA)
NA [2] 
(NA to NA)
Change at Cycle 53/Day 1 (n=0,1,0,0)
NA [2] 
(NA to NA)
-0.2 [1] 
(NA to NA)
NA [2] 
(NA to NA)
NA [2] 
(NA to NA)
Change at Cycle 55/Day 1 (n=0,1,0,0)
NA [2] 
(NA to NA)
-0.3 [1] 
(NA to NA)
NA [2] 
(NA to NA)
NA [2] 
(NA to NA)
Change at Cycle 57/Day 1 (n=0,1,0,0)
NA [2] 
(NA to NA)
0.0 [1] 
(NA to NA)
NA [2] 
(NA to NA)
NA [2] 
(NA to NA)
Change at Cycle 59/Day 1 (n=0,1,0,0)
NA [2] 
(NA to NA)
-0.2 [1] 
(NA to NA)
NA [2] 
(NA to NA)
NA [2] 
(NA to NA)
Change at Cycle 61/Day 1 (n=0,1,0,0)
NA [2] 
(NA to NA)
0.0 [1] 
(NA to NA)
NA [2] 
(NA to NA)
NA [2] 
(NA to NA)
Change at Cycle 63/Day 1 (n=0,0,0,0)
NA [2] 
(NA to NA)
NA [2] 
(NA to NA)
NA [2] 
(NA to NA)
NA [2] 
(NA to NA)
Change at Cycle 65/Day 1 (n=0,1,0,0)
NA [2] 
(NA to NA)
-0.2 [1] 
(NA to NA)
NA [2] 
(NA to NA)
NA [2] 
(NA to NA)
Change at end of treatment (n=21,29,26,21)
1.3
(0.5 to 2.1)
1.0
(0.3 to 1.6)
1.5
(0.2 to 2.8)
1.2
(0.0 to 2.4)
[1]
95% confidence interval was not estimable since only one participant was evaluable.
[2]
Data was not analyzed as no participants were evaluable for the particular cycle.
Time Frame [Not Specified]
Adverse Event Reporting Description The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
 
Arm/Group Title Axitinib + FOLFIRI Bevacizumab + FOLFIRI Axitinib + FOLFOX Bevacizumab + FOLFOX
Hide Arm/Group Description Axitinib (AG-013736) tablet starting dose 5 milligram (mg) orally twice daily (BID) along with combination chemotherapy of irinotecan, 5- flurouracil (5-FU) and leucovorin (LV) (FOLFIRI) regimen consisting of irinotecan 180 mg per square meter (mg/m^2) 90 minutes intravenous (IV) infusion, concurrently with LV 400 mg/m^2 (or levo-leucovarin [l-LV] 200 mg /m^2) 2 hours (hrs) IV infusion followed immediately by 5-FU 400 mg/m^2 IV bolus injection and a subsequent 5-FU 2400 mg/m^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle. Bevacizumab 5mg/kilogram (kg) 30-90 minutes IV infusion (based on tolerance) every 2 weeks along with FOLFIRI regimen consisting of irinotecan 180 mg/m^2 90 minutes IV infusion, concurrently with LV 400 mg/m^2 (or l-LV 200 mg /m^2) 2 hrs IV infusion followed immediately by 5-FU 400 mg/m^2 IV bolus injection and a subsequent 5-FU 2400 mg/m^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle. Axitinib (AG-013736) tablet starting dose 5 mg BID along with combination chemotherapy of oxaliplatin, LV and 5-FU (FOLFOX) regimen consisting of oxaliplatin 85 mg/m^2 120 minutes IV infusion, concurrently with LV 400 mg/m^2 (or l-LV 200 mg /m^2) 2 hrs IV infusion followed immediately by 5-FU 400 mg/m^2 IV bolus injection and a subsequent 5-FU 2400 mg/m^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle. Bevacizumab 5mg/kg 30-90 minutes IV infusion (based on tolerance) every 2 weeks along with FOLFOX regimen consisting of oxaliplatin 85 mg/m^2 120 minutes IV infusion, concurrently with LV 400 mg/m^2 (or l-LV 200 mg /m^2) 2 hrs IV infusion followed immediately by 5-FU 400 mg/m^2 IV bolus injection and a subsequent 5-FU 2400 mg/m^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle.
All-Cause Mortality
Axitinib + FOLFIRI Bevacizumab + FOLFIRI Axitinib + FOLFOX Bevacizumab + FOLFOX
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Axitinib + FOLFIRI Bevacizumab + FOLFIRI Axitinib + FOLFOX Bevacizumab + FOLFOX
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   17/46 (36.96%)   9/51 (17.65%)   11/36 (30.56%)   5/35 (14.29%) 
Blood and lymphatic system disorders         
Anaemia * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Febrile neutropenia * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Neutropenia * 1  0/46 (0.00%)  1/51 (1.96%)  0/36 (0.00%)  0/35 (0.00%) 
Cardiac disorders         
Atrial fibrillation * 1  0/46 (0.00%)  0/51 (0.00%)  1/36 (2.78%)  0/35 (0.00%) 
Ear and labyrinth disorders         
Otosalpingitis * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Gastrointestinal disorders         
Abdominal pain * 1  2/46 (4.35%)  0/51 (0.00%)  1/36 (2.78%)  0/35 (0.00%) 
Abdominal pain upper * 1  0/46 (0.00%)  1/51 (1.96%)  1/36 (2.78%)  0/35 (0.00%) 
Colonic obstruction * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Diarrhoea * 1  3/46 (6.52%)  2/51 (3.92%)  0/36 (0.00%)  1/35 (2.86%) 
Gastrointestinal haemorrhage * 1  0/46 (0.00%)  1/51 (1.96%)  0/36 (0.00%)  0/35 (0.00%) 
Haematochezia * 1  0/46 (0.00%)  0/51 (0.00%)  0/36 (0.00%)  1/35 (2.86%) 
Ileal ulcer * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Ileus * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Nausea * 1  2/46 (4.35%)  1/51 (1.96%)  0/36 (0.00%)  0/35 (0.00%) 
Oesophagitis * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Rectal perforation * 1  0/46 (0.00%)  0/51 (0.00%)  1/36 (2.78%)  0/35 (0.00%) 
Stomatitis * 1  0/46 (0.00%)  1/51 (1.96%)  0/36 (0.00%)  0/35 (0.00%) 
Vomiting * 1  1/46 (2.17%)  2/51 (3.92%)  1/36 (2.78%)  0/35 (0.00%) 
Anal inflammation * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Subileus * 1  1/46 (2.17%)  1/51 (1.96%)  0/36 (0.00%)  0/35 (0.00%) 
Haemorrhagic ascites * 1  0/46 (0.00%)  0/51 (0.00%)  1/36 (2.78%)  0/35 (0.00%) 
Gastrointestinal ulcer * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
General disorders         
Asthenia * 1  2/46 (4.35%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Fatigue * 1  2/46 (4.35%)  0/51 (0.00%)  1/36 (2.78%)  0/35 (0.00%) 
Performance status decreased * 1  0/46 (0.00%)  0/51 (0.00%)  1/36 (2.78%)  0/35 (0.00%) 
General physical health deterioration * 1  1/46 (2.17%)  0/51 (0.00%)  1/36 (2.78%)  0/35 (0.00%) 
Disease progression * 1  2/46 (4.35%)  3/51 (5.88%)  0/36 (0.00%)  0/35 (0.00%) 
Hepatobiliary disorders         
Hyperbilirubinaemia * 1  2/46 (4.35%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Hepatic mass * 1  0/46 (0.00%)  0/51 (0.00%)  1/36 (2.78%)  0/35 (0.00%) 
Bile duct stone * 1  0/46 (0.00%)  0/51 (0.00%)  1/36 (2.78%)  0/35 (0.00%) 
Infections and infestations         
Cellulitis pharyngeal * 1  0/46 (0.00%)  0/51 (0.00%)  1/36 (2.78%)  0/35 (0.00%) 
Escherichia sepsis * 1  0/46 (0.00%)  0/51 (0.00%)  0/36 (0.00%)  1/35 (2.86%) 
Pneumonia * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Sepsis * 1  1/46 (2.17%)  1/51 (1.96%)  0/36 (0.00%)  0/35 (0.00%) 
Anal abscess * 1  0/46 (0.00%)  0/51 (0.00%)  1/36 (2.78%)  0/35 (0.00%) 
Lung infection * 1  0/46 (0.00%)  0/51 (0.00%)  0/36 (0.00%)  1/35 (2.86%) 
Injury, poisoning and procedural complications         
Lumbar vertebral fracture * 1  0/46 (0.00%)  1/51 (1.96%)  0/36 (0.00%)  0/35 (0.00%) 
Metabolism and nutrition disorders         
Dehydration * 1  4/46 (8.70%)  0/51 (0.00%)  1/36 (2.78%)  0/35 (0.00%) 
Hypovolaemia * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Musculoskeletal and connective tissue disorders         
Back pain * 1  0/46 (0.00%)  0/51 (0.00%)  0/36 (0.00%)  1/35 (2.86%) 
Nervous system disorders         
Cerebral haemorrhage * 1  0/46 (0.00%)  0/51 (0.00%)  1/36 (2.78%)  0/35 (0.00%) 
Headache * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Peripheral sensory neuropathy * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Psychiatric disorders         
Depression * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Renal and urinary disorders         
Renal failure acute * 1  0/46 (0.00%)  0/51 (0.00%)  1/36 (2.78%)  0/35 (0.00%) 
Respiratory, thoracic and mediastinal disorders         
Hypoxia * 1  0/46 (0.00%)  0/51 (0.00%)  0/36 (0.00%)  1/35 (2.86%) 
Pneumothorax * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Pulmonary embolism * 1  2/46 (4.35%)  1/51 (1.96%)  0/36 (0.00%)  0/35 (0.00%) 
Vascular disorders         
Hypertension * 1  0/46 (0.00%)  0/51 (0.00%)  0/36 (0.00%)  1/35 (2.86%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Axitinib + FOLFIRI Bevacizumab + FOLFIRI Axitinib + FOLFOX Bevacizumab + FOLFOX
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   45/46 (97.83%)   51/51 (100.00%)   35/36 (97.22%)   33/35 (94.29%) 
Blood and lymphatic system disorders         
Anaemia * 1  6/46 (13.04%)  11/51 (21.57%)  4/36 (11.11%)  5/35 (14.29%) 
Coagulopathy * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Febrile neutropenia * 1  0/46 (0.00%)  1/51 (1.96%)  0/36 (0.00%)  0/35 (0.00%) 
Leukopenia * 1  6/46 (13.04%)  6/51 (11.76%)  5/36 (13.89%)  2/35 (5.71%) 
Lymphopenia * 1  0/46 (0.00%)  0/51 (0.00%)  0/36 (0.00%)  2/35 (5.71%) 
Neutropenia * 1  20/46 (43.48%)  27/51 (52.94%)  20/36 (55.56%)  10/35 (28.57%) 
Thrombocytopenia * 1  3/46 (6.52%)  4/51 (7.84%)  8/36 (22.22%)  5/35 (14.29%) 
Cardiac disorders         
Cardiac failure congestive * 1  0/46 (0.00%)  0/51 (0.00%)  0/36 (0.00%)  1/35 (2.86%) 
Left ventricular dysfunction * 1  0/46 (0.00%)  0/51 (0.00%)  0/36 (0.00%)  2/35 (5.71%) 
Tachycardia * 1  1/46 (2.17%)  0/51 (0.00%)  1/36 (2.78%)  1/35 (2.86%) 
Ear and labyrinth disorders         
Ear discomfort * 1  0/46 (0.00%)  0/51 (0.00%)  1/36 (2.78%)  0/35 (0.00%) 
Ear disorder * 1  0/46 (0.00%)  0/51 (0.00%)  0/36 (0.00%)  1/35 (2.86%) 
Ear pain * 1  1/46 (2.17%)  1/51 (1.96%)  0/36 (0.00%)  0/35 (0.00%) 
External ear inflammation * 1  0/46 (0.00%)  1/51 (1.96%)  0/36 (0.00%)  0/35 (0.00%) 
Hyperacusis * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Otosalpingitis * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Tinnitus * 1  0/46 (0.00%)  0/51 (0.00%)  1/36 (2.78%)  0/35 (0.00%) 
Vertigo * 1  1/46 (2.17%)  1/51 (1.96%)  0/36 (0.00%)  0/35 (0.00%) 
Endocrine disorders         
Hyperthyroidism * 1  0/46 (0.00%)  0/51 (0.00%)  1/36 (2.78%)  0/35 (0.00%) 
Hypothyroidism * 1  7/46 (15.22%)  0/51 (0.00%)  9/36 (25.00%)  1/35 (2.86%) 
Eye disorders         
Age-related macular degeneration * 1  0/46 (0.00%)  0/51 (0.00%)  0/36 (0.00%)  1/35 (2.86%) 
Asthenopia * 1  0/46 (0.00%)  0/51 (0.00%)  0/36 (0.00%)  1/35 (2.86%) 
Cataract * 1  1/46 (2.17%)  1/51 (1.96%)  0/36 (0.00%)  1/35 (2.86%) 
Conjunctival oedema * 1  0/46 (0.00%)  0/51 (0.00%)  0/36 (0.00%)  1/35 (2.86%) 
Conjunctivitis * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Dry eye * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  1/35 (2.86%) 
Eye discharge * 1  0/46 (0.00%)  1/51 (1.96%)  0/36 (0.00%)  0/35 (0.00%) 
Eye haemorrhage * 1  0/46 (0.00%)  0/51 (0.00%)  1/36 (2.78%)  0/35 (0.00%) 
Eye irritation * 1  0/46 (0.00%)  1/51 (1.96%)  0/36 (0.00%)  0/35 (0.00%) 
Eye pain * 1  0/46 (0.00%)  0/51 (0.00%)  0/36 (0.00%)  2/35 (5.71%) 
Eye pruritus * 1  0/46 (0.00%)  0/51 (0.00%)  1/36 (2.78%)  0/35 (0.00%) 
Lacrimation increased * 1  0/46 (0.00%)  0/51 (0.00%)  1/36 (2.78%)  0/35 (0.00%) 
Mydriasis * 1  0/46 (0.00%)  0/51 (0.00%)  0/36 (0.00%)  1/35 (2.86%) 
Vision blurred * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Visual impairment * 1  0/46 (0.00%)  0/51 (0.00%)  0/36 (0.00%)  1/35 (2.86%) 
Gastrointestinal disorders         
Abdominal discomfort * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Abdominal distension * 1  1/46 (2.17%)  0/51 (0.00%)  1/36 (2.78%)  1/35 (2.86%) 
Abdominal pain * 1  12/46 (26.09%)  11/51 (21.57%)  7/36 (19.44%)  9/35 (25.71%) 
Abdominal pain lower * 1  1/46 (2.17%)  1/51 (1.96%)  0/36 (0.00%)  0/35 (0.00%) 
Abdominal pain upper * 1  5/46 (10.87%)  6/51 (11.76%)  0/36 (0.00%)  2/35 (5.71%) 
Anal fissure * 1  2/46 (4.35%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Anal haemorrhage * 1  1/46 (2.17%)  1/51 (1.96%)  0/36 (0.00%)  0/35 (0.00%) 
Anal inflammation * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Anorectal discomfort * 1  0/46 (0.00%)  2/51 (3.92%)  0/36 (0.00%)  0/35 (0.00%) 
Ascites * 1  0/46 (0.00%)  1/51 (1.96%)  0/36 (0.00%)  0/35 (0.00%) 
Chapped lips * 1  0/46 (0.00%)  0/51 (0.00%)  0/36 (0.00%)  1/35 (2.86%) 
Cheilitis * 1  2/46 (4.35%)  0/51 (0.00%)  1/36 (2.78%)  0/35 (0.00%) 
Constipation * 1  7/46 (15.22%)  16/51 (31.37%)  3/36 (8.33%)  10/35 (28.57%) 
Defaecation urgency * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Dental discomfort * 1  0/46 (0.00%)  1/51 (1.96%)  0/36 (0.00%)  0/35 (0.00%) 
Diarrhoea * 1  32/46 (69.57%)  25/51 (49.02%)  15/36 (41.67%)  11/35 (31.43%) 
Dry mouth * 1  3/46 (6.52%)  1/51 (1.96%)  1/36 (2.78%)  2/35 (5.71%) 
Dyspepsia * 1  7/46 (15.22%)  5/51 (9.80%)  1/36 (2.78%)  0/35 (0.00%) 
Dysphagia * 1  2/46 (4.35%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Enteritis * 1  0/46 (0.00%)  1/51 (1.96%)  0/36 (0.00%)  0/35 (0.00%) 
Epigastric discomfort * 1  1/46 (2.17%)  0/51 (0.00%)  1/36 (2.78%)  0/35 (0.00%) 
Eructation * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Faecal incontinence * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Faeces discoloured * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Flatulence * 1  1/46 (2.17%)  1/51 (1.96%)  1/36 (2.78%)  0/35 (0.00%) 
Gastritis * 1  3/46 (6.52%)  2/51 (3.92%)  1/36 (2.78%)  2/35 (5.71%) 
Gastrointestinal toxicity * 1  0/46 (0.00%)  0/51 (0.00%)  0/36 (0.00%)  1/35 (2.86%) 
Gastrooesophageal reflux disease * 1  1/46 (2.17%)  2/51 (3.92%)  0/36 (0.00%)  0/35 (0.00%) 
Gingival pain * 1  1/46 (2.17%)  0/51 (0.00%)  1/36 (2.78%)  0/35 (0.00%) 
Gingivitis * 1  3/46 (6.52%)  2/51 (3.92%)  0/36 (0.00%)  0/35 (0.00%) 
Haemorrhoidal haemorrhage * 1  0/46 (0.00%)  1/51 (1.96%)  0/36 (0.00%)  0/35 (0.00%) 
Haemorrhoids * 1  4/46 (8.70%)  2/51 (3.92%)  0/36 (0.00%)  0/35 (0.00%) 
Hernial eventration * 1  0/46 (0.00%)  1/51 (1.96%)  0/36 (0.00%)  0/35 (0.00%) 
Intestinal obstruction * 1  1/46 (2.17%)  1/51 (1.96%)  0/36 (0.00%)  1/35 (2.86%) 
Large intestinal haemorrhage * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Lip ulceration * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Mouth ulceration * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  1/35 (2.86%) 
Nausea * 1  27/46 (58.70%)  30/51 (58.82%)  18/36 (50.00%)  16/35 (45.71%) 
Odynophagia * 1  1/46 (2.17%)  1/51 (1.96%)  0/36 (0.00%)  1/35 (2.86%) 
Oesophagitis * 1  3/46 (6.52%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Oral pain * 1  2/46 (4.35%)  1/51 (1.96%)  2/36 (5.56%)  0/35 (0.00%) 
Painful defaecation * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Periodontitis * 1  0/46 (0.00%)  1/51 (1.96%)  1/36 (2.78%)  0/35 (0.00%) 
Peristalsis visible * 1  0/46 (0.00%)  0/51 (0.00%)  1/36 (2.78%)  0/35 (0.00%) 
Proctalgia * 1  6/46 (13.04%)  2/51 (3.92%)  1/36 (2.78%)  0/35 (0.00%) 
Proctitis * 1  2/46 (4.35%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Rectal fissure * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Rectal haemorrhage * 1  4/46 (8.70%)  3/51 (5.88%)  0/36 (0.00%)  3/35 (8.57%) 
Rectal tenesmus * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Stomatitis * 1  11/46 (23.91%)  7/51 (13.73%)  9/36 (25.00%)  7/35 (20.00%) 
Subileus * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Tooth erosion * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Toothache * 1  0/46 (0.00%)  3/51 (5.88%)  0/36 (0.00%)  1/35 (2.86%) 
Vomiting * 1  22/46 (47.83%)  18/51 (35.29%)  12/36 (33.33%)  3/35 (8.57%) 
General disorders         
Asthenia * 1  13/46 (28.26%)  11/51 (21.57%)  6/36 (16.67%)  6/35 (17.14%) 
Chest discomfort * 1  0/46 (0.00%)  0/51 (0.00%)  0/36 (0.00%)  1/35 (2.86%) 
Chest pain * 1  1/46 (2.17%)  3/51 (5.88%)  1/36 (2.78%)  1/35 (2.86%) 
Chills * 1  2/46 (4.35%)  1/51 (1.96%)  2/36 (5.56%)  2/35 (5.71%) 
Device occlusion * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Fatigue * 1  21/46 (45.65%)  18/51 (35.29%)  12/36 (33.33%)  9/35 (25.71%) 
Implant site haematoma * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Influenza like illness * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Infusion site extravasation * 1  0/46 (0.00%)  1/51 (1.96%)  0/36 (0.00%)  0/35 (0.00%) 
Injection site reaction * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Mucosal dryness * 1  0/46 (0.00%)  0/51 (0.00%)  0/36 (0.00%)  1/35 (2.86%) 
Mucosal inflammation * 1  7/46 (15.22%)  11/51 (21.57%)  4/36 (11.11%)  3/35 (8.57%) 
Oedema * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Oedema peripheral * 1  7/46 (15.22%)  2/51 (3.92%)  0/36 (0.00%)  1/35 (2.86%) 
Pain * 1  0/46 (0.00%)  1/51 (1.96%)  3/36 (8.33%)  1/35 (2.86%) 
Performance status decreased * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Pyrexia * 1  5/46 (10.87%)  7/51 (13.73%)  5/36 (13.89%)  3/35 (8.57%) 
Temperature intolerance * 1  0/46 (0.00%)  0/51 (0.00%)  1/36 (2.78%)  0/35 (0.00%) 
Thrombosis in device * 1  0/46 (0.00%)  0/51 (0.00%)  1/36 (2.78%)  0/35 (0.00%) 
Hepatobiliary disorders         
Cholangitis * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Hepatic function abnormal * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Hepatic pain * 1  0/46 (0.00%)  0/51 (0.00%)  1/36 (2.78%)  0/35 (0.00%) 
Hyperbilirubinaemia * 1  3/46 (6.52%)  1/51 (1.96%)  1/36 (2.78%)  2/35 (5.71%) 
Hyperplastic cholecystopathy * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Jaundice * 1  0/46 (0.00%)  1/51 (1.96%)  0/36 (0.00%)  0/35 (0.00%) 
Jaundice cholestatic * 1  0/46 (0.00%)  0/51 (0.00%)  0/36 (0.00%)  1/35 (2.86%) 
Portal vein thrombosis * 1  0/46 (0.00%)  1/51 (1.96%)  0/36 (0.00%)  0/35 (0.00%) 
Immune system disorders         
Drug hypersensitivity * 1  0/46 (0.00%)  0/51 (0.00%)  1/36 (2.78%)  0/35 (0.00%) 
Hypersensitivity * 1  0/46 (0.00%)  1/51 (1.96%)  5/36 (13.89%)  1/35 (2.86%) 
Seasonal allergy * 1  0/46 (0.00%)  0/51 (0.00%)  1/36 (2.78%)  0/35 (0.00%) 
Infections and infestations         
Anal abscess * 1  0/46 (0.00%)  1/51 (1.96%)  0/36 (0.00%)  1/35 (2.86%) 
Bronchitis * 1  0/46 (0.00%)  1/51 (1.96%)  0/36 (0.00%)  2/35 (5.71%) 
Clostridial infection * 1  0/46 (0.00%)  1/51 (1.96%)  0/36 (0.00%)  0/35 (0.00%) 
Clostridium difficile colitis * 1  0/46 (0.00%)  0/51 (0.00%)  1/36 (2.78%)  0/35 (0.00%) 
Colostomy infection * 1  0/46 (0.00%)  0/51 (0.00%)  1/36 (2.78%)  0/35 (0.00%) 
Cystitis * 1  0/46 (0.00%)  2/51 (3.92%)  1/36 (2.78%)  0/35 (0.00%) 
Device related infection * 1  1/46 (2.17%)  1/51 (1.96%)  1/36 (2.78%)  0/35 (0.00%) 
Ear infection * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Gastroenteritis * 1  2/46 (4.35%)  1/51 (1.96%)  0/36 (0.00%)  1/35 (2.86%) 
Herpes simplex * 1  1/46 (2.17%)  1/51 (1.96%)  0/36 (0.00%)  0/35 (0.00%) 
Herpes zoster * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Hordeolum * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Infected sebaceous cyst * 1  0/46 (0.00%)  0/51 (0.00%)  0/36 (0.00%)  1/35 (2.86%) 
Infection * 1  0/46 (0.00%)  0/51 (0.00%)  1/36 (2.78%)  0/35 (0.00%) 
Influenza * 1  0/46 (0.00%)  2/51 (3.92%)  1/36 (2.78%)  1/35 (2.86%) 
Laryngitis * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Lung infection * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Nasopharyngitis * 1  3/46 (6.52%)  5/51 (9.80%)  0/36 (0.00%)  2/35 (5.71%) 
Oral candidiasis * 1  0/46 (0.00%)  0/51 (0.00%)  1/36 (2.78%)  0/35 (0.00%) 
Oral herpes * 1  1/46 (2.17%)  1/51 (1.96%)  0/36 (0.00%)  0/35 (0.00%) 
Pelvic abscess * 1  0/46 (0.00%)  0/51 (0.00%)  1/36 (2.78%)  0/35 (0.00%) 
Pharyngitis * 1  0/46 (0.00%)  1/51 (1.96%)  0/36 (0.00%)  0/35 (0.00%) 
Pneumonia * 1  0/46 (0.00%)  1/51 (1.96%)  0/36 (0.00%)  0/35 (0.00%) 
Respiratory tract infection * 1  0/46 (0.00%)  0/51 (0.00%)  0/36 (0.00%)  1/35 (2.86%) 
Rhinitis * 1  0/46 (0.00%)  3/51 (5.88%)  0/36 (0.00%)  1/35 (2.86%) 
Septic shock * 1  0/46 (0.00%)  1/51 (1.96%)  0/36 (0.00%)  0/35 (0.00%) 
Sinusitis * 1  1/46 (2.17%)  1/51 (1.96%)  0/36 (0.00%)  0/35 (0.00%) 
Tonsillitis * 1  1/46 (2.17%)  1/51 (1.96%)  0/36 (0.00%)  0/35 (0.00%) 
Tooth abscess * 1  0/46 (0.00%)  1/51 (1.96%)  0/36 (0.00%)  0/35 (0.00%) 
Upper respiratory tract infection * 1  1/46 (2.17%)  3/51 (5.88%)  0/36 (0.00%)  0/35 (0.00%) 
Urinary tract infection * 1  3/46 (6.52%)  3/51 (5.88%)  2/36 (5.56%)  1/35 (2.86%) 
Viral upper respiratory tract infection * 1  2/46 (4.35%)  3/51 (5.88%)  0/36 (0.00%)  1/35 (2.86%) 
Injury, poisoning and procedural complications         
Anal injury * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Contusion * 1  0/46 (0.00%)  2/51 (3.92%)  0/36 (0.00%)  0/35 (0.00%) 
Excoriation * 1  0/46 (0.00%)  1/51 (1.96%)  0/36 (0.00%)  0/35 (0.00%) 
Face injury * 1  0/46 (0.00%)  0/51 (0.00%)  1/36 (2.78%)  0/35 (0.00%) 
Post procedural haemorrhage * 1  0/46 (0.00%)  2/51 (3.92%)  1/36 (2.78%)  0/35 (0.00%) 
Scapula fracture * 1  0/46 (0.00%)  0/51 (0.00%)  0/36 (0.00%)  1/35 (2.86%) 
Sunburn * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Thermal burn * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Tooth fracture * 1  0/46 (0.00%)  0/51 (0.00%)  0/36 (0.00%)  1/35 (2.86%) 
Upper limb fracture * 1  0/46 (0.00%)  0/51 (0.00%)  0/36 (0.00%)  1/35 (2.86%) 
Investigations         
Alanine aminotransferase * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  3/35 (8.57%) 
Alanine aminotransferase increased * 1  3/46 (6.52%)  2/51 (3.92%)  1/36 (2.78%)  2/35 (5.71%) 
Aspartate aminotransferase * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  3/35 (8.57%) 
Aspartate aminotransferase increased * 1  2/46 (4.35%)  2/51 (3.92%)  1/36 (2.78%)  2/35 (5.71%) 
Blood albumin decreased * 1  2/46 (4.35%)  1/51 (1.96%)  0/36 (0.00%)  0/35 (0.00%) 
Blood alkaline phosphatase * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  1/35 (2.86%) 
Blood alkaline phosphatase increased * 1  4/46 (8.70%)  0/51 (0.00%)  0/36 (0.00%)  2/35 (5.71%) 
Blood bilirubin * 1  0/46 (0.00%)  0/51 (0.00%)  0/36 (0.00%)  1/35 (2.86%) 
Blood bilirubin increased * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Blood cholesterol increased * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Blood creatine increased * 1  0/46 (0.00%)  0/51 (0.00%)  0/36 (0.00%)  1/35 (2.86%) 
Blood creatinine * 1  0/46 (0.00%)  0/51 (0.00%)  0/36 (0.00%)  1/35 (2.86%) 
Blood glucose increased * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Blood lactate dehydrogenase increased * 1  0/46 (0.00%)  0/51 (0.00%)  0/36 (0.00%)  1/35 (2.86%) 
Blood potassium decreased * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Blood pressure increased * 1  0/46 (0.00%)  1/51 (1.96%)  0/36 (0.00%)  0/35 (0.00%) 
Blood thyroid stimulating hormone increased * 1  4/46 (8.70%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Blood triglycerides increased * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Breath sounds abnormal * 1  0/46 (0.00%)  0/51 (0.00%)  1/36 (2.78%)  2/35 (5.71%) 
Carcinoembryonic antigen increased * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Clostridium test positive * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Gamma-glutamyltransferase increased * 1  0/46 (0.00%)  1/51 (1.96%)  0/36 (0.00%)  0/35 (0.00%) 
General physical condition normal * 1  0/46 (0.00%)  0/51 (0.00%)  0/36 (0.00%)  1/35 (2.86%) 
Haemoglobin * 1  0/46 (0.00%)  0/51 (0.00%)  1/36 (2.78%)  2/35 (5.71%) 
Haemoglobin decreased * 1  3/46 (6.52%)  5/51 (9.80%)  3/36 (8.33%)  0/35 (0.00%) 
Lymphocyte count decreased * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Neutrophil count * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  2/35 (5.71%) 
Neutrophil count decreased * 1  4/46 (8.70%)  3/51 (5.88%)  3/36 (8.33%)  2/35 (5.71%) 
Platelet count * 1  0/46 (0.00%)  0/51 (0.00%)  1/36 (2.78%)  2/35 (5.71%) 
Platelet count decreased * 1  2/46 (4.35%)  2/51 (3.92%)  4/36 (11.11%)  3/35 (8.57%) 
Visual field tests * 1  0/46 (0.00%)  1/51 (1.96%)  0/36 (0.00%)  0/35 (0.00%) 
Weight decreased * 1  13/46 (28.26%)  4/51 (7.84%)  5/36 (13.89%)  2/35 (5.71%) 
Weight increased * 1  0/46 (0.00%)  1/51 (1.96%)  1/36 (2.78%)  0/35 (0.00%) 
White blood cell count * 1  0/46 (0.00%)  0/51 (0.00%)  0/36 (0.00%)  1/35 (2.86%) 
White blood cell count decreased * 1  2/46 (4.35%)  0/51 (0.00%)  1/36 (2.78%)  0/35 (0.00%) 
White blood cell count increased * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Metabolism and nutrition disorders         
Decreased appetite * 1  24/46 (52.17%)  16/51 (31.37%)  13/36 (36.11%)  7/35 (20.00%) 
Dehydration * 1  7/46 (15.22%)  1/51 (1.96%)  1/36 (2.78%)  0/35 (0.00%) 
Hypercalcaemia * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Hypercholesterolaemia * 1  1/46 (2.17%)  0/51 (0.00%)  1/36 (2.78%)  1/35 (2.86%) 
Hyperglycaemia * 1  0/46 (0.00%)  1/51 (1.96%)  2/36 (5.56%)  2/35 (5.71%) 
Hyperkalaemia * 1  1/46 (2.17%)  1/51 (1.96%)  0/36 (0.00%)  2/35 (5.71%) 
Hypoalbuminaemia * 1  2/46 (4.35%)  0/51 (0.00%)  1/36 (2.78%)  0/35 (0.00%) 
Hypocalcaemia * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Hypoglycaemia * 1  0/46 (0.00%)  0/51 (0.00%)  1/36 (2.78%)  0/35 (0.00%) 
Hypokalaemia * 1  4/46 (8.70%)  3/51 (5.88%)  3/36 (8.33%)  2/35 (5.71%) 
Hypomagnesaemia * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Hyponatraemia * 1  0/46 (0.00%)  0/51 (0.00%)  1/36 (2.78%)  0/35 (0.00%) 
Lactic acidosis * 1  0/46 (0.00%)  0/51 (0.00%)  0/36 (0.00%)  1/35 (2.86%) 
Metabolic acidosis * 1  0/46 (0.00%)  0/51 (0.00%)  0/36 (0.00%)  1/35 (2.86%) 
Musculoskeletal and connective tissue disorders         
Arthralgia * 1  2/46 (4.35%)  1/51 (1.96%)  2/36 (5.56%)  3/35 (8.57%) 
Back pain * 1  3/46 (6.52%)  6/51 (11.76%)  2/36 (5.56%)  2/35 (5.71%) 
Bone pain * 1  0/46 (0.00%)  3/51 (5.88%)  0/36 (0.00%)  0/35 (0.00%) 
Flank pain * 1  2/46 (4.35%)  1/51 (1.96%)  0/36 (0.00%)  1/35 (2.86%) 
Muscle atrophy * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Muscle contracture * 1  0/46 (0.00%)  0/51 (0.00%)  1/36 (2.78%)  1/35 (2.86%) 
Muscle spasms * 1  2/46 (4.35%)  0/51 (0.00%)  1/36 (2.78%)  0/35 (0.00%) 
Muscular weakness * 1  0/46 (0.00%)  1/51 (1.96%)  0/36 (0.00%)  0/35 (0.00%) 
Musculoskeletal chest pain * 1  0/46 (0.00%)  2/51 (3.92%)  0/36 (0.00%)  1/35 (2.86%) 
Musculoskeletal disorder * 1  0/46 (0.00%)  0/51 (0.00%)  0/36 (0.00%)  1/35 (2.86%) 
Musculoskeletal pain * 1  2/46 (4.35%)  2/51 (3.92%)  0/36 (0.00%)  1/35 (2.86%) 
Myalgia * 1  0/46 (0.00%)  3/51 (5.88%)  1/36 (2.78%)  1/35 (2.86%) 
Neck pain * 1  0/46 (0.00%)  0/51 (0.00%)  1/36 (2.78%)  0/35 (0.00%) 
Osteoarthritis * 1  0/46 (0.00%)  0/51 (0.00%)  1/36 (2.78%)  0/35 (0.00%) 
Pain in extremity * 1  4/46 (8.70%)  0/51 (0.00%)  1/36 (2.78%)  0/35 (0.00%) 
Spinal osteoarthritis * 1  0/46 (0.00%)  0/51 (0.00%)  1/36 (2.78%)  0/35 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Cancer pain * 1  0/46 (0.00%)  1/51 (1.96%)  0/36 (0.00%)  0/35 (0.00%) 
Malignant pleural effusion * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Tumour haemorrhage * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Nervous system disorders         
Ageusia * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Aphasia * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Cerebral ischaemia * 1  0/46 (0.00%)  0/51 (0.00%)  0/36 (0.00%)  1/35 (2.86%) 
Cholinergic syndrome * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Dizziness * 1  1/46 (2.17%)  3/51 (5.88%)  3/36 (8.33%)  2/35 (5.71%) 
Dysaesthesia * 1  0/46 (0.00%)  0/51 (0.00%)  1/36 (2.78%)  1/35 (2.86%) 
Dysgeusia * 1  5/46 (10.87%)  1/51 (1.96%)  3/36 (8.33%)  4/35 (11.43%) 
Headache * 1  6/46 (13.04%)  4/51 (7.84%)  7/36 (19.44%)  3/35 (8.57%) 
Hyperaesthesia * 1  0/46 (0.00%)  0/51 (0.00%)  0/36 (0.00%)  1/35 (2.86%) 
Hypoaesthesia * 1  0/46 (0.00%)  2/51 (3.92%)  0/36 (0.00%)  0/35 (0.00%) 
Myelopathy * 1  0/46 (0.00%)  0/51 (0.00%)  0/36 (0.00%)  1/35 (2.86%) 
Neuropathy peripheral * 1  3/46 (6.52%)  4/51 (7.84%)  7/36 (19.44%)  16/35 (45.71%) 
Paraesthesia * 1  0/46 (0.00%)  2/51 (3.92%)  4/36 (11.11%)  3/35 (8.57%) 
Peripheral sensory neuropathy * 1  2/46 (4.35%)  4/51 (7.84%)  4/36 (11.11%)  5/35 (14.29%) 
Somnolence * 1  0/46 (0.00%)  1/51 (1.96%)  1/36 (2.78%)  0/35 (0.00%) 
Syncope * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Toxic neuropathy * 1  0/46 (0.00%)  0/51 (0.00%)  0/36 (0.00%)  1/35 (2.86%) 
Transient ischaemic attack * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Psychiatric disorders         
Agitation * 1  0/46 (0.00%)  1/51 (1.96%)  0/36 (0.00%)  0/35 (0.00%) 
Anxiety * 1  3/46 (6.52%)  3/51 (5.88%)  1/36 (2.78%)  1/35 (2.86%) 
Confusional state * 1  0/46 (0.00%)  1/51 (1.96%)  0/36 (0.00%)  1/35 (2.86%) 
Delirium * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Depression * 1  5/46 (10.87%)  3/51 (5.88%)  2/36 (5.56%)  0/35 (0.00%) 
Disorientation * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Insomnia * 1  3/46 (6.52%)  2/51 (3.92%)  2/36 (5.56%)  3/35 (8.57%) 
Mood altered * 1  0/46 (0.00%)  0/51 (0.00%)  1/36 (2.78%)  0/35 (0.00%) 
Nervousness * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Sleep disorder * 1  0/46 (0.00%)  1/51 (1.96%)  0/36 (0.00%)  0/35 (0.00%) 
Renal and urinary disorders         
Bladder spasm * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Chromaturia * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Dysuria * 1  2/46 (4.35%)  1/51 (1.96%)  3/36 (8.33%)  4/35 (11.43%) 
Glycosuria * 1  0/46 (0.00%)  0/51 (0.00%)  0/36 (0.00%)  1/35 (2.86%) 
Haematuria * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Hydronephrosis * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Proteinuria * 1  8/46 (17.39%)  5/51 (9.80%)  2/36 (5.56%)  3/35 (8.57%) 
Renal failure * 1  0/46 (0.00%)  0/51 (0.00%)  1/36 (2.78%)  0/35 (0.00%) 
Ureteric obstruction * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Urinary incontinence * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Urinary retention * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Reproductive system and breast disorders         
Dysmenorrhoea * 1  0/46 (0.00%)  1/51 (1.96%)  0/36 (0.00%)  0/35 (0.00%) 
Epididymitis * 1  0/46 (0.00%)  0/51 (0.00%)  1/36 (2.78%)  0/35 (0.00%) 
Erectile dysfunction * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Gynaecomastia * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Metrorrhagia * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  1/35 (2.86%) 
Ovarian cyst * 1  0/46 (0.00%)  1/51 (1.96%)  0/36 (0.00%)  0/35 (0.00%) 
Pelvic pain * 1  0/46 (0.00%)  1/51 (1.96%)  0/36 (0.00%)  1/35 (2.86%) 
Uterine haemorrhage * 1  0/46 (0.00%)  1/51 (1.96%)  0/36 (0.00%)  0/35 (0.00%) 
Vaginal discharge * 1  0/46 (0.00%)  0/51 (0.00%)  1/36 (2.78%)  0/35 (0.00%) 
Vaginal haemorrhage * 1  1/46 (2.17%)  1/51 (1.96%)  0/36 (0.00%)  0/35 (0.00%) 
Vulvovaginal pain * 1  0/46 (0.00%)  0/51 (0.00%)  1/36 (2.78%)  0/35 (0.00%) 
Vulvovaginal pruritus * 1  0/46 (0.00%)  1/51 (1.96%)  0/36 (0.00%)  0/35 (0.00%) 
Respiratory, thoracic and mediastinal disorders         
Bronchospasm * 1  0/46 (0.00%)  1/51 (1.96%)  0/36 (0.00%)  0/35 (0.00%) 
Cough * 1  7/46 (15.22%)  5/51 (9.80%)  3/36 (8.33%)  4/35 (11.43%) 
Dysphonia * 1  6/46 (13.04%)  2/51 (3.92%)  4/36 (11.11%)  1/35 (2.86%) 
Dyspnoea * 1  8/46 (17.39%)  3/51 (5.88%)  4/36 (11.11%)  0/35 (0.00%) 
Dyspnoea exertional * 1  0/46 (0.00%)  0/51 (0.00%)  0/36 (0.00%)  1/35 (2.86%) 
Epistaxis * 1  11/46 (23.91%)  15/51 (29.41%)  4/36 (11.11%)  5/35 (14.29%) 
Hiccups * 1  2/46 (4.35%)  1/51 (1.96%)  0/36 (0.00%)  0/35 (0.00%) 
Lung disorder * 1  0/46 (0.00%)  1/51 (1.96%)  0/36 (0.00%)  0/35 (0.00%) 
Nasal discomfort * 1  0/46 (0.00%)  1/51 (1.96%)  0/36 (0.00%)  0/35 (0.00%) 
Nasal disorder * 1  0/46 (0.00%)  0/51 (0.00%)  1/36 (2.78%)  1/35 (2.86%) 
Nasal ulcer * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Oropharyngeal discomfort * 1  0/46 (0.00%)  1/51 (1.96%)  0/36 (0.00%)  0/35 (0.00%) 
Oropharyngeal pain * 1  2/46 (4.35%)  5/51 (9.80%)  1/36 (2.78%)  1/35 (2.86%) 
Painful respiration * 1  0/46 (0.00%)  0/51 (0.00%)  1/36 (2.78%)  0/35 (0.00%) 
Paranasal sinus hypersecretion * 1  0/46 (0.00%)  1/51 (1.96%)  0/36 (0.00%)  1/35 (2.86%) 
Pneumonitis * 1  0/46 (0.00%)  0/51 (0.00%)  0/36 (0.00%)  1/35 (2.86%) 
Productive cough * 1  1/46 (2.17%)  2/51 (3.92%)  0/36 (0.00%)  1/35 (2.86%) 
Pulmonary artery thrombosis * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Pulmonary embolism * 1  0/46 (0.00%)  1/51 (1.96%)  0/36 (0.00%)  1/35 (2.86%) 
Reflux laryngitis * 1  0/46 (0.00%)  0/51 (0.00%)  0/36 (0.00%)  1/35 (2.86%) 
Respiratory alkalosis * 1  0/46 (0.00%)  0/51 (0.00%)  0/36 (0.00%)  1/35 (2.86%) 
Rhinitis allergic * 1  1/46 (2.17%)  0/51 (0.00%)  1/36 (2.78%)  1/35 (2.86%) 
Rhinorrhoea * 1  2/46 (4.35%)  2/51 (3.92%)  0/36 (0.00%)  0/35 (0.00%) 
Sinus congestion * 1  0/46 (0.00%)  1/51 (1.96%)  1/36 (2.78%)  0/35 (0.00%) 
Throat irritation * 1  0/46 (0.00%)  1/51 (1.96%)  0/36 (0.00%)  0/35 (0.00%) 
Throat tightness * 1  0/46 (0.00%)  0/51 (0.00%)  1/36 (2.78%)  0/35 (0.00%) 
Wheezing * 1  0/46 (0.00%)  0/51 (0.00%)  1/36 (2.78%)  0/35 (0.00%) 
Skin and subcutaneous tissue disorders         
Acne * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Alopecia * 1  6/46 (13.04%)  12/51 (23.53%)  2/36 (5.56%)  0/35 (0.00%) 
Dermatitis * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Dermatitis allergic * 1  1/46 (2.17%)  0/51 (0.00%)  1/36 (2.78%)  1/35 (2.86%) 
Dry skin * 1  2/46 (4.35%)  0/51 (0.00%)  1/36 (2.78%)  2/35 (5.71%) 
Eczema * 1  0/46 (0.00%)  0/51 (0.00%)  0/36 (0.00%)  1/35 (2.86%) 
Erythema * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  1/35 (2.86%) 
Facial wasting * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  1/35 (2.86%) 
Hyperhidrosis * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  1/35 (2.86%) 
Nail disorder * 1  1/46 (2.17%)  0/51 (0.00%)  1/36 (2.78%)  2/35 (5.71%) 
Nail toxicity * 1  0/46 (0.00%)  1/51 (1.96%)  0/36 (0.00%)  0/35 (0.00%) 
Night sweats * 1  0/46 (0.00%)  1/51 (1.96%)  1/36 (2.78%)  0/35 (0.00%) 
Palmar-plantar erythrodysaesthesia syndrome * 1  8/46 (17.39%)  3/51 (5.88%)  4/36 (11.11%)  2/35 (5.71%) 
Pruritus * 1  3/46 (6.52%)  2/51 (3.92%)  4/36 (11.11%)  1/35 (2.86%) 
Rash * 1  5/46 (10.87%)  2/51 (3.92%)  3/36 (8.33%)  1/35 (2.86%) 
Rash pruritic * 1  0/46 (0.00%)  2/51 (3.92%)  0/36 (0.00%)  0/35 (0.00%) 
Skin discolouration * 1  0/46 (0.00%)  0/51 (0.00%)  1/36 (2.78%)  0/35 (0.00%) 
Skin disorder * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Skin hyperpigmentation * 1  0/46 (0.00%)  0/51 (0.00%)  1/36 (2.78%)  0/35 (0.00%) 
Skin lesion * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Skin toxicity * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Subcutaneous nodule * 1  0/46 (0.00%)  1/51 (1.96%)  0/36 (0.00%)  0/35 (0.00%) 
Urticaria * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Vascular disorders         
Deep vein thrombosis * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Embolism * 1  0/46 (0.00%)  0/51 (0.00%)  0/36 (0.00%)  1/35 (2.86%) 
Embolism venous * 1  0/46 (0.00%)  1/51 (1.96%)  0/36 (0.00%)  0/35 (0.00%) 
Flushing * 1  0/46 (0.00%)  0/51 (0.00%)  0/36 (0.00%)  1/35 (2.86%) 
Haematoma * 1  0/46 (0.00%)  0/51 (0.00%)  1/36 (2.78%)  0/35 (0.00%) 
Haemorrhage * 1  0/46 (0.00%)  0/51 (0.00%)  1/36 (2.78%)  0/35 (0.00%) 
Hypertension * 1  17/46 (36.96%)  8/51 (15.69%)  24/36 (66.67%)  6/35 (17.14%) 
Hypotension * 1  3/46 (6.52%)  1/51 (1.96%)  2/36 (5.56%)  2/35 (5.71%) 
Pallor * 1  0/46 (0.00%)  0/51 (0.00%)  1/36 (2.78%)  0/35 (0.00%) 
Phlebitis * 1  1/46 (2.17%)  2/51 (3.92%)  0/36 (0.00%)  0/35 (0.00%) 
Thrombophlebitis superficial * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Thrombosis * 1  1/46 (2.17%)  0/51 (0.00%)  0/36 (0.00%)  0/35 (0.00%) 
Vasculitis * 1  0/46 (0.00%)  0/51 (0.00%)  0/36 (0.00%)  1/35 (2.86%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Results Point of Contact
Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc.
Phone: 1-800-718-1021
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00615056     History of Changes
Other Study ID Numbers: A4061034
First Submitted: February 1, 2008
First Posted: February 14, 2008
Results First Submitted: March 28, 2012
Results First Posted: April 20, 2012
Last Update Posted: April 19, 2013