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Study to Evaluate Motesanib With or Without Carboplatin/Paclitaxel or Panitumumab in the Treatment of Patients With Advanced Non-Small Cell Lung Cancer (NSCLC)

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ClinicalTrials.gov Identifier: NCT00094835
Recruitment Status : Completed
First Posted : October 27, 2004
Results First Posted : March 24, 2014
Last Update Posted : March 24, 2016
Sponsor:
Information provided by (Responsible Party):
Amgen

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Lung Cancer
Non-Small Cell Lung Cancer
Interventions Biological: Panitumumab
Drug: Motesanib diphosphate
Drug: Paclitaxel
Drug: Carboplatin
Enrollment 51
Recruitment Details Participants were enrolled from 18 January 2005 through 25 September 2006
Pre-assignment Details  
Arm/Group Title Paclitaxel/Carboplatin + Motesanib 50 mg QD Paclitaxel/Carboplatin + Motesanib 125 mg QD Paclitaxel/Carboplatin + Motesanib 75 mg BID Panitumumab + Motesanib 50 mg QD Panitumumab + Motesanib 125 mg QD Panitumumab + Motesanib 75 mg BID Panitumumab + Paclitaxel/Carboplatin + Motesanib 125 mg QD
Hide Arm/Group Description Chemotherapy naïve participants received paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by intravenous (IV) infusion on Day 1 of each 21-day cycle, and motesanib, 50 mg once daily (QD) orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. Chemotherapy naïve participants received paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by intravenous (IV) infusion on Day 1 of each 21-day cycle, and motesanib, 125 mg QD orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. Chemotherapy naïve participants received paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by intravenous (IV) infusion on Day 1 of each 21-day cycle, and motesanib, 75 mg twice daily (BID) orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. Participants with no more than one prior chemotherapy regimen for NSCLC received panitumumab 9.0 mg/kg IV on Day 1 of each 21-day cycle, and motesanib 50 mg QD, orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. Participants with no more than one prior chemotherapy regimen for NSCLC received panitumumab 9.0 mg/kg IV on Day 1 of each 21-day cycle, and motesanib 125 mg QD, orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. Participants with no more than one prior chemotherapy regimen for NSCLC received panitumumab 9.0 mg/kg IV on Day 1 of each 21-day cycle, and motesanib 75 mg BID, orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. Chemotherapy naïve participants received panitumumab 9.0 mg/kg, paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by IV infusion on Day 1 of each 21-day cycle, and motesanib 125 mg QD, orally on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter.
Period Title: Overall Study
Started 9 11 7 5 7 6 6
Treated With Motesanib 6 11 6 4 7 5 6
Completed 5 8 4 4 3 3 4
Not Completed 4 3 3 1 4 3 2
Reason Not Completed
Physician Decision             1             0             0             0             0             1             0
Withdrawal by Subject             0             0             0             0             0             0             1
Lost to Follow-up             0             0             0             0             1             0             0
Death             1             0             0             0             1             0             0
Non-compliance             1             2             2             0             2             2             1
Other             1             1             1             1             0             0             0
Arm/Group Title Paclitaxel/Carboplatin + Motesanib 50 mg QD Paclitaxel/Carboplatin + Motesanib 125 mg QD Paclitaxel/Carboplatin + Motesanib 75 mg BID Panitumumab + Motesanib 50 mg QD Panitumumab + Motesanib 125 mg QD Panitumumab + Motesanib 75 mg BID Panitumumab + Paclitaxel/Carboplatin + Motesanib 125 mg QD Total
Hide Arm/Group Description Chemotherapy naïve participants received paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by intravenous (IV) infusion on Day 1 of each 21-day cycle, and motesanib, 50 mg once daily (QD) orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. Chemotherapy naïve participants received paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by intravenous (IV) infusion on Day 1 of each 21-day cycle, and motesanib, 125 mg QD orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. Chemotherapy naïve participants received paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by intravenous (IV) infusion on Day 1 of each 21-day cycle, and motesanib, 75 mg twice daily (BID) orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. Participants with no more than one prior chemotherapy regimen for NSCLC received panitumumab 9.0 mg/kg IV on Day 1 of each 21-day cycle, and motesanib 50 mg QD, orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. Participants with no more than one prior chemotherapy regimen for NSCLC received panitumumab 9.0 mg/kg IV on Day 1 of each 21-day cycle, and motesanib 125 mg QD, orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. Participants with no more than one prior chemotherapy regimen for NSCLC received panitumumab 9.0 mg/kg IV on Day 1 of each 21-day cycle, and motesanib 75 mg BID, orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. Chemotherapy naïve participants received panitumumab 9.0 mg/kg, paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by IV infusion on Day 1 of each 21-day cycle, and motesanib 125 mg QD, orally on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. Total of all reporting groups
Overall Number of Baseline Participants 6 11 6 4 7 5 6 45
Hide Baseline Analysis Population Description
The analysis is based on the Safety Analysis Set which consists of all consented participants who received at least one dose of motesanib.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 6 participants 11 participants 6 participants 4 participants 7 participants 5 participants 6 participants 45 participants
67.8  (7.8) 55.7  (12.7) 64.5  (6.1) 57.5  (9.9) 64.0  (9.6) 51.6  (14.6) 59.0  (5.5) 59.9  (10.8)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 11 participants 6 participants 4 participants 7 participants 5 participants 6 participants 45 participants
Female
0
   0.0%
4
  36.4%
3
  50.0%
0
   0.0%
5
  71.4%
1
  20.0%
3
  50.0%
16
  35.6%
Male
6
 100.0%
7
  63.6%
3
  50.0%
4
 100.0%
2
  28.6%
4
  80.0%
3
  50.0%
29
  64.4%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 6 participants 11 participants 6 participants 4 participants 7 participants 5 participants 6 participants 45 participants
White or Caucasian 6 11 5 4 6 4 5 41
Asian 0 0 0 0 1 0 1 2
Black or African American 0 0 1 0 0 1 0 2
1.Primary Outcome
Title Time to Maximum Plasma Concentration of Motesanib (Tmax) for Cycle 1
Hide Description The time after dosing that the maximal plasma concentration of motesanib was observed in Cycle 1. For the 75 mg BID cohorts, Tmax is reported for the first daily dose.
Time Frame Cycle 1, Day 3 at predose, 15 and 30 minutes, and at 1, 2, 4, 6, 10 (QD cohorts only), and 24 hours post-dose.
Hide Outcome Measure Data
Hide Analysis Population Description
The pharmacokinetic (PK) population consisted of all consented patients who received motesanib and had evaluable pharmacokinetic data and did not have significant protocol deviations that affected the data or key-dosing information that was missing.
Arm/Group Title Paclitaxel/Carboplatin + Motesanib 50 mg QD Paclitaxel/Carboplatin + Motesanib 125 mg QD Paclitaxel/Carboplatin + Motesanib 75 mg BID Panitumumab + Motesanib 50 mg QD Panitumumab + Motesanib 125 mg QD Panitumumab + Motesanib 75 mg BID Panitumumab + Paclitaxel/Carboplatin + Motesanib 125 mg QD
Hide Arm/Group Description:
Chemotherapy naïve participants received paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by intravenous (IV) infusion on Day 1 of each 21-day cycle, and motesanib, 50 mg once daily (QD) orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter.
Chemotherapy naïve participants received paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by intravenous (IV) infusion on Day 1 of each 21-day cycle, and motesanib, 125 mg QD orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter.
Chemotherapy naïve participants received paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by intravenous (IV) infusion on Day 1 of each 21-day cycle, and motesanib, 75 mg twice daily (BID) orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter.
Participants with no more than one prior chemotherapy regimen for NSCLC received panitumumab 9.0 mg/kg IV on Day 1 of each 21-day cycle, and motesanib 50 mg QD, orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter.
Participants with no more than one prior chemotherapy regimen for NSCLC received panitumumab 9.0 mg/kg IV on Day 1 of each 21-day cycle, and motesanib 125 mg QD, orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter.
Participants with no more than one prior chemotherapy regimen for NSCLC received panitumumab 9.0 mg/kg IV on Day 1 of each 21-day cycle, and motesanib 75 mg BID, orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter.
Chemotherapy naïve participants received panitumumab 9.0 mg/kg, paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by IV infusion on Day 1 of each 21-day cycle, and motesanib 125 mg QD, orally on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter.
Overall Number of Participants Analyzed 4 9 6 4 6 3 3
Median (Full Range)
Unit of Measure: hours
0.75
(0.5 to 2.0)
1.0
(0.5 to 6.0)
0.75
(0.25 to 1.00)
1.5
(0.5 to 4.0)
1.0
(0.5 to 1.0)
0.58
(0.50 to 1.00)
1.0
(1.0 to 4.0)
2.Primary Outcome
Title Maximum Observed Plasma Concentration of Motesanib (Cmax) in Cycle 1
Hide Description The maximal observed plasma concentration of motesanib after a single dose dose in Cycle 1. For the 75 mg BID cohorts, Cmax is reported for the first daily dose.
Time Frame Cycle 1, Day 3 at predose, 15 and 30 min, and at 1, 2, 4, 6, 10 (QD cohorts only), and 24 hours post-dose.
Hide Outcome Measure Data
Hide Analysis Population Description
PK population
Arm/Group Title Paclitaxel/Carboplatin + Motesanib 50 mg QD Paclitaxel/Carboplatin + Motesanib 125 mg QD Paclitaxel/Carboplatin + Motesanib 75 mg BID Panitumumab + Motesanib 50 mg QD Panitumumab + Motesanib 125 mg QD Panitumumab + Motesanib 75 mg BID Panitumumab + Paclitaxel/Carboplatin + Motesanib 125 mg QD
Hide Arm/Group Description:
Chemotherapy naïve participants received paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by intravenous (IV) infusion on Day 1 of each 21-day cycle, and motesanib, 50 mg once daily (QD) orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter.
Chemotherapy naïve participants received paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by intravenous (IV) infusion on Day 1 of each 21-day cycle, and motesanib, 125 mg QD orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter.
Chemotherapy naïve participants received paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by intravenous (IV) infusion on Day 1 of each 21-day cycle, and motesanib, 75 mg twice daily (BID) orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter.
Participants with no more than one prior chemotherapy regimen for NSCLC received panitumumab 9.0 mg/kg IV on Day 1 of each 21-day cycle, and motesanib 50 mg QD, orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter.
Participants with no more than one prior chemotherapy regimen for NSCLC received panitumumab 9.0 mg/kg IV on Day 1 of each 21-day cycle, and motesanib 125 mg QD, orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter.
Participants with no more than one prior chemotherapy regimen for NSCLC received panitumumab 9.0 mg/kg IV on Day 1 of each 21-day cycle, and motesanib 75 mg BID, orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter.
Chemotherapy naïve participants received panitumumab 9.0 mg/kg, paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by IV infusion on Day 1 of each 21-day cycle, and motesanib 125 mg QD, orally on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter.
Overall Number of Participants Analyzed 4 9 6 4 6 3 3
Mean (Standard Deviation)
Unit of Measure: ng/mL
158  (55) 525  (250) 448  (112) 328  (214) 444  (130) 198  (55) 360  (243)
3.Primary Outcome
Title Estimated Terminal-phase Half-life (t1/2,z) of Motesanib in Cycle 1
Hide Description The terminal-phase elimination half-life (t1/2,z) of motesanib was calculated as ln(2)/λz. The terminal elimination rate constant (λz) was determined by linear regression of the natural logarithms of at least the last 3 measurable concentrations during the terminal phase. For the 75 mg BID cohorts, t1/2,z is reported for the first daily dose.
Time Frame Cycle 1, Day 3 at predose, 15 and 30 min, and at 1, 2, 4, 6, 10 (QD cohorts only), and 24 hours postdose.
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population. Participants with elevated motesanib concentrations at 24 hours were excluded from the calculations. Summary results are not presented for the Panitumumab + Paclitaxel/Carboplatin + Motesanib 125 mg QD treatment group for which the sample size was smaller than 3.
Arm/Group Title Paclitaxel/Carboplatin + Motesanib 50 mg QD Paclitaxel/Carboplatin + Motesanib 125 mg QD Paclitaxel/Carboplatin + Motesanib 75 mg BID Panitumumab + Motesanib 50 mg QD Panitumumab + Motesanib 125 mg QD Panitumumab + Motesanib 75 mg BID
Hide Arm/Group Description:
Chemotherapy naïve participants received paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by intravenous (IV) infusion on Day 1 of each 21-day cycle, and motesanib, 50 mg once daily (QD) orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter.
Chemotherapy naïve participants received paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by intravenous (IV) infusion on Day 1 of each 21-day cycle, and motesanib, 125 mg QD orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter.
Chemotherapy naïve participants received paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by intravenous (IV) infusion on Day 1 of each 21-day cycle, and motesanib, 75 mg twice daily (BID) orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter.
Participants with no more than one prior chemotherapy regimen for NSCLC received panitumumab 9.0 mg/kg IV on Day 1 of each 21-day cycle, and motesanib 50 mg QD, orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter.
Participants with no more than one prior chemotherapy regimen for NSCLC received panitumumab 9.0 mg/kg IV on Day 1 of each 21-day cycle, and motesanib 125 mg QD, orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter.
Participants with no more than one prior chemotherapy regimen for NSCLC received panitumumab 9.0 mg/kg IV on Day 1 of each 21-day cycle, and motesanib 75 mg BID, orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter.
Overall Number of Participants Analyzed 3 7 6 4 4 3
Mean (Standard Deviation)
Unit of Measure: hours
7.34  (2.07) 5.33  (1.05) 5.77  (1.45) 6.47  (2.31) 7.57  (2.60) 8.28  (2.62)
4.Primary Outcome
Title Area Under the Plasma Concentration-time Curve for Motesanib in Cycle 1
Hide Description Area under the plasma concentration-time curve for motesanib in Cycle 1 calculated using the using the linear/log trapezoidal method. AUC from time zero to infinity (AUC0-inf) is reported for the 50 and 125 mg QD cohorts and AUC from time 0 to 24 hours post-dose (AUC0-24) is reported for the 75 mg BID cohort, where AUC0-24 is the sum of AUC0-12 for the first and second daily dose.
Time Frame Cycle 1, Day 3 at predose, 15 and 30 minutes, and at 1, 2, 4, 6, 10 (QD cohorts only), and 24 hours post-dose.
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population. Participants with elevated motesanib concentrations at 24 hours were excluded from the calculations. Summary results are not presented for the Panitumumab + Paclitaxel/Carboplatin + Motesanib 125 mg QD treatment group for which the sample size was smaller than 3.
Arm/Group Title Paclitaxel/Carboplatin + Motesanib 50 mg QD Paclitaxel/Carboplatin + Motesanib 125 mg QD Paclitaxel/Carboplatin + Motesanib 75 mg BID Panitumumab + Motesanib 50 mg QD Panitumumab + Motesanib 125 mg QD Panitumumab + Motesanib 75 mg BID
Hide Arm/Group Description:
Chemotherapy naïve participants received paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by intravenous (IV) infusion on Day 1 of each 21-day cycle, and motesanib, 50 mg once daily (QD) orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter.
Chemotherapy naïve participants received paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by intravenous (IV) infusion on Day 1 of each 21-day cycle, and motesanib, 125 mg QD orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter.
Chemotherapy naïve participants received paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by intravenous (IV) infusion on Day 1 of each 21-day cycle, and motesanib, 75 mg twice daily (BID) orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter.
Participants with no more than one prior chemotherapy regimen for NSCLC received panitumumab 9.0 mg/kg IV on Day 1 of each 21-day cycle, and motesanib 50 mg QD, orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter.
Participants with no more than one prior chemotherapy regimen for NSCLC received panitumumab 9.0 mg/kg IV on Day 1 of each 21-day cycle, and motesanib 125 mg QD, orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter.
Participants with no more than one prior chemotherapy regimen for NSCLC received panitumumab 9.0 mg/kg IV on Day 1 of each 21-day cycle, and motesanib 75 mg BID, orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter.
Overall Number of Participants Analyzed 3 7 5 4 4 3
Mean (Standard Deviation)
Unit of Measure: μg*hr/mL
0.971  (0.300) 3.21  (1.12) 2.91  (1.01) 1.74  (0.63) 3.23  (1.83) 2.04  (1.06)
5.Primary Outcome
Title Trough Plasma Concentration at 24 Hours Post-dose (C24) for Motesanib in Cycle 1
Hide Description The trough plasma concentration for motesanib at 24 hours postdose in Cycle 1. For the 75 BID cohort, C24 is the observed concentration at 24 hours (ie, after the second daily dose).
Time Frame Cycle 1, Day 3, 24 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population. Participants with elevated motesanib concentrations at 24 hours were excluded from the calculations. Summary results are not presented for the Panitumumab + Paclitaxel/Carboplatin + Motesanib 125 mg QD treatment group for which the sample size was smaller than 3.
Arm/Group Title Paclitaxel/Carboplatin + Motesanib 50 mg QD Paclitaxel/Carboplatin + Motesanib 125 mg QD Paclitaxel/Carboplatin + Motesanib 75 mg BID Panitumumab + Motesanib 50 mg QD Panitumumab + Motesanib 125 mg QD Panitumumab + Motesanib 75 mg BID
Hide Arm/Group Description:
Chemotherapy naïve participants received paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by intravenous (IV) infusion on Day 1 of each 21-day cycle, and motesanib, 50 mg once daily (QD) orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter.
Chemotherapy naïve participants received paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by intravenous (IV) infusion on Day 1 of each 21-day cycle, and motesanib, 125 mg QD orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter.
Chemotherapy naïve participants received paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by intravenous (IV) infusion on Day 1 of each 21-day cycle, and motesanib, 75 mg twice daily (BID) orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter.
Participants with no more than one prior chemotherapy regimen for NSCLC received panitumumab 9.0 mg/kg IV on Day 1 of each 21-day cycle, and motesanib 50 mg QD, orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter.
Participants with no more than one prior chemotherapy regimen for NSCLC received panitumumab 9.0 mg/kg IV on Day 1 of each 21-day cycle, and motesanib 125 mg QD, orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter.
Participants with no more than one prior chemotherapy regimen for NSCLC received panitumumab 9.0 mg/kg IV on Day 1 of each 21-day cycle, and motesanib 75 mg BID, orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter.
Overall Number of Participants Analyzed 3 9 5 4 4 3
Mean (Standard Deviation)
Unit of Measure: ng/mL
9.12  (4.17) 26.5  (16.8) 56.7  (27.4) 14.0  (11.7) 32.5  (21.5) 56.8  (21.1)
6.Primary Outcome
Title Time to Maximum Plasma Concentration of Motesanib (Tmax) in Cycle 2
Hide Description The time after dosing that the maximal plasma concentration of motesanib was observed in Cycle 2. For the 75 mg BID cohorts, Tmax is reported for the first daily dose.
Time Frame Cycle 2, Day 1 at predose, 15 and 30 min, and at 1, 2, 4, 6, 10 (QD cohorts only), and 24 hours post-dose.
Hide Outcome Measure Data
Hide Analysis Population Description
PK population
Arm/Group Title Paclitaxel/Carboplatin + Motesanib 50 mg QD Paclitaxel/Carboplatin + Motesanib 125 mg QD Paclitaxel/Carboplatin + Motesanib 75 mg BID Panitumumab + Motesanib 50 mg QD Panitumumab + Motesanib 125 mg QD Panitumumab + Motesanib 75 mg BID Panitumumab + Paclitaxel/Carboplatin + Motesanib 125 mg QD
Hide Arm/Group Description:
Chemotherapy naïve participants received paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by intravenous (IV) infusion on Day 1 of each 21-day cycle, and motesanib, 50 mg once daily (QD) orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter.
Chemotherapy naïve participants received paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by intravenous (IV) infusion on Day 1 of each 21-day cycle, and motesanib, 125 mg QD orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter.
Chemotherapy naïve participants received paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by intravenous (IV) infusion on Day 1 of each 21-day cycle, and motesanib, 75 mg twice daily (BID) orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter.
Participants with no more than one prior chemotherapy regimen for NSCLC received panitumumab 9.0 mg/kg IV on Day 1 of each 21-day cycle, and motesanib 50 mg QD, orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter.
Participants with no more than one prior chemotherapy regimen for NSCLC received panitumumab 9.0 mg/kg IV on Day 1 of each 21-day cycle, and motesanib 125 mg QD, orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter.
Participants with no more than one prior chemotherapy regimen for NSCLC received panitumumab 9.0 mg/kg IV on Day 1 of each 21-day cycle, and motesanib 75 mg BID, orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter.
Chemotherapy naïve participants received panitumumab 9.0 mg/kg, paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by IV infusion on Day 1 of each 21-day cycle, and motesanib 125 mg QD, orally on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter.
Overall Number of Participants Analyzed 4 9 6 4 6 3 3
Median (Full Range)
Unit of Measure: hours
1.5
(1.0 to 2.0)
1.0
(0.5 to 4.0)
0.63
(0.25 to 4.0)
1.0
(0.5 to 2.0)
0.75
(0.25 to 2.0)
1.0
(0.50 to 2.0)
2.0
(0.5 to 2.0)
7.Primary Outcome
Title Maximum Observed Plasma Concentration of Motesanib (Cmax) in Cycle 2
Hide Description The maximal observed plasma concentration of motesanib in Cycle 2, after multiple doses. For the 75 mg BID cohorts, Cmax is reported for the first daily dose.
Time Frame Cycle 2, Day 1 at predose, 15 and 30 min, and at 1, 2, 4, 6, 10 (QD cohorts only), and 24 hours post-dose.
Hide Outcome Measure Data
Hide Analysis Population Description
PK population
Arm/Group Title Paclitaxel/Carboplatin + Motesanib 50 mg QD Paclitaxel/Carboplatin + Motesanib 125 mg QD Paclitaxel/Carboplatin + Motesanib 75 mg BID Panitumumab + Motesanib 50 mg QD Panitumumab + Motesanib 125 mg QD Panitumumab + Motesanib 75 mg BID Panitumumab + Paclitaxel/Carboplatin + Motesanib 125 mg QD
Hide Arm/Group Description:
Chemotherapy naïve participants received paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by intravenous (IV) infusion on Day 1 of each 21-day cycle, and motesanib, 50 mg once daily (QD) orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter.
Chemotherapy naïve participants received paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by intravenous (IV) infusion on Day 1 of each 21-day cycle, and motesanib, 125 mg QD orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter.
Chemotherapy naïve participants received paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by intravenous (IV) infusion on Day 1 of each 21-day cycle, and motesanib, 75 mg twice daily (BID) orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter.
Participants with no more than one prior chemotherapy regimen for NSCLC received panitumumab 9.0 mg/kg IV on Day 1 of each 21-day cycle, and motesanib 50 mg QD, orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter.
Participants with no more than one prior chemotherapy regimen for NSCLC received panitumumab 9.0 mg/kg IV on Day 1 of each 21-day cycle, and motesanib 125 mg QD, orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter.
Participants with no more than one prior chemotherapy regimen for NSCLC received panitumumab 9.0 mg/kg IV on Day 1 of each 21-day cycle, and motesanib 75 mg BID, orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter.
Chemotherapy naïve participants received panitumumab 9.0 mg/kg, paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by IV infusion on Day 1 of each 21-day cycle, and motesanib 125 mg QD, orally on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter.
Overall Number of Participants Analyzed 4 9 6 4 6 3 3
Mean (Standard Deviation)
Unit of Measure: ng/mL
148  (25) 748  (701) 390  (319) 265  (190) 672  (336) 242  (153) 651  (605)
8.Primary Outcome
Title Estimated Terminal-phase Half-life (t1/2,z) of Motesanib in Cycle 2
Hide Description The terminal-phase elimination half-life (t1/2,z) of motesanib was calculated as ln(2)/λz. The terminal elimination rate constant (λz) was determined by linear regression of the natural logarithms of at least the last 3 measurable concentrations during the terminal phase. For the 75 mg BID cohorts, t1/2,z is reported for the first daily dose.
Time Frame Cycle 2, Day 1 at predose, 15 and 30 min, and at 1, 2, 4, 6, 10 (QD cohorts only), and 24 hours post-dose.
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population. Participants with elevated motesanib concentrations at 24 hours were excluded from the calculations. Summary results are not presented for three treatment groups for which the sample size was smaller than 3.
Arm/Group Title Paclitaxel/Carboplatin + Motesanib 125 mg QD Paclitaxel/Carboplatin + Motesanib 75 mg BID Panitumumab + Motesanib 50 mg QD Panitumumab + Motesanib 125 mg QD
Hide Arm/Group Description:
Chemotherapy naïve participants received paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by intravenous (IV) infusion on Day 1 of each 21-day cycle, and motesanib, 125 mg QD orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter.
Chemotherapy naïve participants received paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by intravenous (IV) infusion on Day 1 of each 21-day cycle, and motesanib, 75 mg twice daily (BID) orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter.
Participants with no more than one prior chemotherapy regimen for NSCLC received panitumumab 9.0 mg/kg IV on Day 1 of each 21-day cycle, and motesanib 50 mg QD, orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter.
Participants with no more than one prior chemotherapy regimen for NSCLC received panitumumab 9.0 mg/kg IV on Day 1 of each 21-day cycle, and motesanib 125 mg QD, orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter.
Overall Number of Participants Analyzed 5 5 3 3
Mean (Standard Deviation)
Unit of Measure: hours
6.41  (2.08) 6.36  (1.70) 7.08  (0.35) 4.90  (1.21)
9.Primary Outcome
Title Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours Post-dose for Motesanib in Cycle 2
Hide Description Area under the plasma concentration-time curve from time 0 to 24 hours post-dose (AUC0-24) for motesanib in Cycle 2 calculated using the using the linear/log trapezoidal method. For the 75 mg BID cohort AUC0-24 is the sum of AUC0-12 for the first and second daily dose.
Time Frame Cycle 2, Day 1 at predose, 15 and 30 minutes, and at 1, 2, 4, 6, 10 (QD cohorts only), and 24 hours post-dose.
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population. Participants with elevated motesanib concentrations at 24 hours were excluded from the calculations. Summary results are not presented for two treatment groups for which the sample size was smaller than 3.
Arm/Group Title Paclitaxel/Carboplatin + Motesanib 125 mg QD Paclitaxel/Carboplatin + Motesanib 75 mg BID Panitumumab + Motesanib 50 mg QD Panitumumab + Motesanib 125 mg QD Panitumumab + Paclitaxel/Carboplatin + Motesanib 125 mg QD
Hide Arm/Group Description:
Chemotherapy naïve participants received paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by intravenous (IV) infusion on Day 1 of each 21-day cycle, and motesanib, 125 mg QD orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter.
Chemotherapy naïve participants received paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by intravenous (IV) infusion on Day 1 of each 21-day cycle, and motesanib, 75 mg twice daily (BID) orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter.
Participants with no more than one prior chemotherapy regimen for NSCLC received panitumumab 9.0 mg/kg IV on Day 1 of each 21-day cycle, and motesanib 50 mg QD, orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter.
Participants with no more than one prior chemotherapy regimen for NSCLC received panitumumab 9.0 mg/kg IV on Day 1 of each 21-day cycle, and motesanib 125 mg QD, orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter.
Chemotherapy naïve participants received panitumumab 9.0 mg/kg, paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by IV infusion on Day 1 of each 21-day cycle, and motesanib 125 mg QD, orally on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter.
Overall Number of Participants Analyzed 5 5 3 5 3
Mean (Standard Deviation)
Unit of Measure: μg*hr/mL
4.50  (2.62) 3.11  (2.38) 1.26  (0.61) 3.92  (2.65) 3.16  (1.20)
10.Primary Outcome
Title Trough Plasma Concentration at 24 Hours Post-dose (C24) for Motesanib in Cycle 2
Hide Description The trough plasma concentration for motesanib at 24 hours postdose in Cycle 2. For the 75 BID cohort, C24 is the observed concentration at 24 hours (ie, after the second daily dose).
Time Frame Cycle 2, Day 1, 24 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population. Participants with elevated motesanib concentrations at 24 hours were excluded from the calculations. Summary results are not presented for two treatment groups for which the sample size was smaller than 3.
Arm/Group Title Paclitaxel/Carboplatin + Motesanib 125 mg QD Paclitaxel/Carboplatin + Motesanib 75 mg BID Panitumumab + Motesanib 50 mg QD Panitumumab + Motesanib 125 mg QD Panitumumab + Paclitaxel/Carboplatin + Motesanib 125 mg QD
Hide Arm/Group Description:
Chemotherapy naïve participants received paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by intravenous (IV) infusion on Day 1 of each 21-day cycle, and motesanib, 125 mg QD orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter.
Chemotherapy naïve participants received paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by intravenous (IV) infusion on Day 1 of each 21-day cycle, and motesanib, 75 mg twice daily (BID) orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter.
Participants with no more than one prior chemotherapy regimen for NSCLC received panitumumab 9.0 mg/kg IV on Day 1 of each 21-day cycle, and motesanib 50 mg QD, orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter.
Participants with no more than one prior chemotherapy regimen for NSCLC received panitumumab 9.0 mg/kg IV on Day 1 of each 21-day cycle, and motesanib 125 mg QD, orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter.
Chemotherapy naïve participants received panitumumab 9.0 mg/kg, paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by IV infusion on Day 1 of each 21-day cycle, and motesanib 125 mg QD, orally on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter.
Overall Number of Participants Analyzed 5 5 3 5 3
Mean (Standard Deviation)
Unit of Measure: ng/mL
43.4  (44.8) 45.4  (35.9) 10.4  (5.3) 61.1  (72.6) 45.1  (37.9)
11.Secondary Outcome
Title Percentage of Participants With an Overall Objective Response
Hide Description Confirmed objective tumor response defined as a complete response (CR) or partial response (PR) using modified Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0. Tumor response was evaluated by computed tomography (CT) scan or magnetic resonance imaging (MRI). Responding disease (CR or PR) was confirmed no less than 4 weeks after the criteria for response were first met. A complete response defined as the disappearance of all target lesions and all non-target lesions, no new lesions and normalization of tumor marker level. Partial response defined as either the disappearance of all target lesions and the persistence of one or more non-target lesion(s) or/and maintenance of tumor marker level above the normal limits, or, at least a 30% decrease in the sum of the longest diamer (LD) of target lesions, taking as reference the baseline sum LD and no new lesions and/or unequivocal progression of existing non-target lesions.
Time Frame After 9 weeks of treatment (at the end of Cycle 3)
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Hide Analysis Population Description
Efficacy analysis set, composed of all enrolled participants who received at least one dose of motesanib in treatment arms 1-3 or at least one dose of motesanib with one dose of panitumumab in treatmnt arms 4-7.
Arm/Group Title Paclitaxel/Carboplatin + Motesanib 50 mg QD Paclitaxel/Carboplatin + Motesanib 125 mg QD Paclitaxel/Carboplatin + Motesanib 75 mg BID Panitumumab + Motesanib 50 mg QD Panitumumab + Motesanib 125 mg QD Panitumumab + Motesanib 75 mg BID Panitumumab + Paclitaxel/Carboplatin + Motesanib 125 mg QD
Hide Arm/Group Description:
Chemotherapy naïve participants received paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by intravenous (IV) infusion on Day 1 of each 21-day cycle, and motesanib, 50 mg once daily (QD) orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter.
Chemotherapy naïve participants received paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by intravenous (IV) infusion on Day 1 of each 21-day cycle, and motesanib, 125 mg QD orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter.
Chemotherapy naïve participants received paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by intravenous (IV) infusion on Day 1 of each 21-day cycle, and motesanib, 75 mg twice daily (BID) orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter.
Participants with no more than one prior chemotherapy regimen for NSCLC received panitumumab 9.0 mg/kg IV on Day 1 of each 21-day cycle, and motesanib 50 mg QD, orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter.
Participants with no more than one prior chemotherapy regimen for NSCLC received panitumumab 9.0 mg/kg IV on Day 1 of each 21-day cycle, and motesanib 125 mg QD, orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter.
Participants with no more than one prior chemotherapy regimen for NSCLC received panitumumab 9.0 mg/kg IV on Day 1 of each 21-day cycle, and motesanib 75 mg BID, orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter.
Chemotherapy naïve participants received panitumumab 9.0 mg/kg, paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by IV infusion on Day 1 of each 21-day cycle, and motesanib 125 mg QD, orally on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter.
Overall Number of Participants Analyzed 6 11 6 4 7 5 6
Measure Type: Number
Unit of Measure: Percentage of participants
33 18 0 0 0 0 17
Time Frame First dose through 30 days after last dose; maximum time on treatment was 322 days.
Adverse Event Reporting Description The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in any treatment arm.
 
Arm/Group Title Paclitaxel/Carboplatin + Motesanib 50 mg QD Paclitaxel/Carboplatin + Motesanib 125 mg QD Paclitaxel/Carboplatin + Motesanib 75 mg BID Panitumumab + Motesanib 50 mg QD Panitumumab + Motesanib 125 mg QD Panitumumab + Motesanib 75 mg BID Panitumumab + Paclitaxel/Carboplatin + Motesanib 125 mg QD
Hide Arm/Group Description Chemotherapy naïve participants received paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by intravenous (IV) infusion on Day 1 of each 21-day cycle, and motesanib, 50 mg once daily (QD) orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. Chemotherapy naïve participants received paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by intravenous (IV) infusion on Day 1 of each 21-day cycle, and motesanib, 125 mg QD orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. Chemotherapy naïve participants received paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by intravenous (IV) infusion on Day 1 of each 21-day cycle, and motesanib, 75 mg twice daily (BID) orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. Participants with no more than one prior chemotherapy regimen for NSCLC received panitumumab 9.0 mg/kg IV on Day 1 of each 21-day cycle, and motesanib 50 mg QD, orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. Participants with no more than one prior chemotherapy regimen for NSCLC received panitumumab 9.0 mg/kg IV on Day 1 of each 21-day cycle, and motesanib 125 mg QD, orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. Participants with no more than one prior chemotherapy regimen for NSCLC received panitumumab 9.0 mg/kg IV on Day 1 of each 21-day cycle, and motesanib 75 mg BID, orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. Chemotherapy naïve participants received panitumumab 9.0 mg/kg, paclitaxel 200 mg/m^2 and carboplatin chemotherapy administered by IV infusion on Day 1 of each 21-day cycle, and motesanib 125 mg QD, orally on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter.
All-Cause Mortality
Paclitaxel/Carboplatin + Motesanib 50 mg QD Paclitaxel/Carboplatin + Motesanib 125 mg QD Paclitaxel/Carboplatin + Motesanib 75 mg BID Panitumumab + Motesanib 50 mg QD Panitumumab + Motesanib 125 mg QD Panitumumab + Motesanib 75 mg BID Panitumumab + Paclitaxel/Carboplatin + Motesanib 125 mg QD
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/--   --/--   --/-- 
Hide Serious Adverse Events
Paclitaxel/Carboplatin + Motesanib 50 mg QD Paclitaxel/Carboplatin + Motesanib 125 mg QD Paclitaxel/Carboplatin + Motesanib 75 mg BID Panitumumab + Motesanib 50 mg QD Panitumumab + Motesanib 125 mg QD Panitumumab + Motesanib 75 mg BID Panitumumab + Paclitaxel/Carboplatin + Motesanib 125 mg QD
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   5/6 (83.33%)   2/11 (18.18%)   3/6 (50.00%)   0/4 (0.00%)   1/7 (14.29%)   4/5 (80.00%)   2/6 (33.33%) 
Blood and lymphatic system disorders               
Anaemia  1  0/6 (0.00%)  0/11 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  1/6 (16.67%) 
Febrile neutropenia  1  1/6 (16.67%)  0/11 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Pancytopenia  1  0/6 (0.00%)  0/11 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Cardiac disorders               
Atrial fibrillation  1  1/6 (16.67%)  0/11 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Endocrine disorders               
Adrenal insufficiency  1  1/6 (16.67%)  0/11 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Gastrointestinal disorders               
Abdominal pain  1  0/6 (0.00%)  0/11 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  1/5 (20.00%)  1/6 (16.67%) 
Diarrhoea  1  0/6 (0.00%)  0/11 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  1/5 (20.00%)  0/6 (0.00%) 
Gastrointestinal haemorrhage  1  0/6 (0.00%)  0/11 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Nausea  1  0/6 (0.00%)  0/11 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  1/5 (20.00%)  1/6 (16.67%) 
Pancreatitis  1  1/6 (16.67%)  0/11 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Vomiting  1  0/6 (0.00%)  0/11 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  1/5 (20.00%)  0/6 (0.00%) 
General disorders               
Fatigue  1  1/6 (16.67%)  0/11 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Non-cardiac chest pain  1  1/6 (16.67%)  0/11 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Pyrexia  1  0/6 (0.00%)  1/11 (9.09%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Hepatobiliary disorders               
Cholecystitis  1  0/6 (0.00%)  0/11 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/7 (0.00%)  2/5 (40.00%)  0/6 (0.00%) 
Infections and infestations               
Pneumonia  1  1/6 (16.67%)  1/11 (9.09%)  0/6 (0.00%)  0/4 (0.00%)  1/7 (14.29%)  0/5 (0.00%)  0/6 (0.00%) 
Staphylococcal sepsis  1  0/6 (0.00%)  0/11 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  1/5 (20.00%)  0/6 (0.00%) 
Urinary tract infection  1  0/6 (0.00%)  0/11 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Injury, poisoning and procedural complications               
Femur fracture  1  0/6 (0.00%)  1/11 (9.09%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Metabolism and nutrition disorders               
Anorexia  1  0/6 (0.00%)  0/11 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  1/5 (20.00%)  0/6 (0.00%) 
Dehydration  1  1/6 (16.67%)  0/11 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Hypovolaemia  1  0/6 (0.00%)  0/11 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)               
Metastases to central nervous system  1  0/6 (0.00%)  1/11 (9.09%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Non-small cell lung cancer  1  0/6 (0.00%)  0/11 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  1/7 (14.29%)  0/5 (0.00%)  0/6 (0.00%) 
Nervous system disorders               
Cognitive disorder  1  0/6 (0.00%)  0/11 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  1/5 (20.00%)  0/6 (0.00%) 
Encephalopathy  1  0/6 (0.00%)  0/11 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  1/5 (20.00%)  0/6 (0.00%) 
Vocal cord paralysis  1  0/6 (0.00%)  1/11 (9.09%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Psychiatric disorders               
Confusional state  1  1/6 (16.67%)  0/11 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Mental status changes  1  0/6 (0.00%)  0/11 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Renal and urinary disorders               
Renal failure acute  1  0/6 (0.00%)  0/11 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  1/5 (20.00%)  0/6 (0.00%) 
Respiratory, thoracic and mediastinal disorders               
Cough  1  1/6 (16.67%)  0/11 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Dyspnoea  1  2/6 (33.33%)  0/11 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Dyspnoea exacerbated  1  0/6 (0.00%)  0/11 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Hypoxia  1  1/6 (16.67%)  0/11 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  1/7 (14.29%)  0/5 (0.00%)  0/6 (0.00%) 
Interstitial lung disease  1  1/6 (16.67%)  0/11 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Pulmonary embolism  1  2/6 (33.33%)  0/11 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  1/6 (16.67%) 
Skin and subcutaneous tissue disorders               
Rash  1  0/6 (0.00%)  1/11 (9.09%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Vascular disorders               
Hypotension  1  1/6 (16.67%)  0/11 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Orthostatic hypotension  1  0/6 (0.00%)  0/11 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 9.0
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Paclitaxel/Carboplatin + Motesanib 50 mg QD Paclitaxel/Carboplatin + Motesanib 125 mg QD Paclitaxel/Carboplatin + Motesanib 75 mg BID Panitumumab + Motesanib 50 mg QD Panitumumab + Motesanib 125 mg QD Panitumumab + Motesanib 75 mg BID Panitumumab + Paclitaxel/Carboplatin + Motesanib 125 mg QD
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   6/6 (100.00%)   11/11 (100.00%)   6/6 (100.00%)   4/4 (100.00%)   7/7 (100.00%)   5/5 (100.00%)   6/6 (100.00%) 
Blood and lymphatic system disorders               
Anaemia  1  1/6 (16.67%)  1/11 (9.09%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  2/5 (40.00%)  1/6 (16.67%) 
Leukopenia  1  0/6 (0.00%)  0/11 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  1/7 (14.29%)  0/5 (0.00%)  0/6 (0.00%) 
Neutropenia  1  0/6 (0.00%)  2/11 (18.18%)  1/6 (16.67%)  0/4 (0.00%)  1/7 (14.29%)  0/5 (0.00%)  0/6 (0.00%) 
Thrombocytopenia  1  1/6 (16.67%)  1/11 (9.09%)  1/6 (16.67%)  0/4 (0.00%)  0/7 (0.00%)  1/5 (20.00%)  0/6 (0.00%) 
Cardiac disorders               
Atrial fibrillation  1  0/6 (0.00%)  0/11 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  1/5 (20.00%)  0/6 (0.00%) 
Conduction disorder  1  0/6 (0.00%)  1/11 (9.09%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Sinus tachycardia  1  1/6 (16.67%)  0/11 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/7 (0.00%)  1/5 (20.00%)  0/6 (0.00%) 
Tachycardia  1  1/6 (16.67%)  1/11 (9.09%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  1/6 (16.67%) 
Ear and labyrinth disorders               
Deafness  1  0/6 (0.00%)  1/11 (9.09%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  2/6 (33.33%) 
Ear discomfort  1  0/6 (0.00%)  0/11 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/7 (0.00%)  1/5 (20.00%)  0/6 (0.00%) 
Eye disorders               
Conjunctivitis  1  0/6 (0.00%)  1/11 (9.09%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Diplopia  1  0/6 (0.00%)  1/11 (9.09%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Dry eye  1  0/6 (0.00%)  0/11 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  1/7 (14.29%)  0/5 (0.00%)  0/6 (0.00%) 
Vision blurred  1  0/6 (0.00%)  1/11 (9.09%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  2/6 (33.33%) 
Gastrointestinal disorders               
Abdominal discomfort  1  1/6 (16.67%)  1/11 (9.09%)  1/6 (16.67%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Abdominal distension  1  0/6 (0.00%)  1/11 (9.09%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  1/6 (16.67%) 
Abdominal pain  1  0/6 (0.00%)  0/11 (0.00%)  1/6 (16.67%)  1/4 (25.00%)  0/7 (0.00%)  2/5 (40.00%)  0/6 (0.00%) 
Abdominal pain lower  1  0/6 (0.00%)  1/11 (9.09%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Abdominal pain upper  1  0/6 (0.00%)  0/11 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  1/5 (20.00%)  0/6 (0.00%) 
Ascites  1  0/6 (0.00%)  0/11 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Change of bowel habit  1  0/6 (0.00%)  0/11 (0.00%)  0/6 (0.00%)  1/4 (25.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Chapped lips  1  0/6 (0.00%)  0/11 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  1/7 (14.29%)  0/5 (0.00%)  0/6 (0.00%) 
Colitis  1  0/6 (0.00%)  0/11 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Constipation  1  2/6 (33.33%)  2/11 (18.18%)  1/6 (16.67%)  0/4 (0.00%)  2/7 (28.57%)  0/5 (0.00%)  1/6 (16.67%) 
Diarrhoea  1  3/6 (50.00%)  7/11 (63.64%)  6/6 (100.00%)  0/4 (0.00%)  5/7 (71.43%)  3/5 (60.00%)  5/6 (83.33%) 
Dyspepsia  1  2/6 (33.33%)  3/11 (27.27%)  1/6 (16.67%)  0/4 (0.00%)  1/7 (14.29%)  1/5 (20.00%)  3/6 (50.00%) 
Dysphagia  1  0/6 (0.00%)  0/11 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Flatulence  1  0/6 (0.00%)  0/11 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  2/6 (33.33%) 
Gastrointestinal pain  1  0/6 (0.00%)  1/11 (9.09%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  1/5 (20.00%)  0/6 (0.00%) 
Gastrooesophageal reflux disease  1  0/6 (0.00%)  1/11 (9.09%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Gingival pain  1  0/6 (0.00%)  0/11 (0.00%)  0/6 (0.00%)  1/4 (25.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Gingival ulceration  1  0/6 (0.00%)  0/11 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  1/6 (16.67%) 
Hyperchlorhydria  1  0/6 (0.00%)  0/11 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Inguinal hernia  1  0/6 (0.00%)  0/11 (0.00%)  0/6 (0.00%)  1/4 (25.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Mouth ulceration  1  0/6 (0.00%)  0/11 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  1/5 (20.00%)  0/6 (0.00%) 
Nausea  1  4/6 (66.67%)  6/11 (54.55%)  5/6 (83.33%)  1/4 (25.00%)  3/7 (42.86%)  2/5 (40.00%)  4/6 (66.67%) 
Odynophagia  1  0/6 (0.00%)  1/11 (9.09%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Oesophagitis  1  1/6 (16.67%)  1/11 (9.09%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Oral pain  1  0/6 (0.00%)  1/11 (9.09%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Stomatitis  1  0/6 (0.00%)  3/11 (27.27%)  2/6 (33.33%)  0/4 (0.00%)  3/7 (42.86%)  1/5 (20.00%)  4/6 (66.67%) 
Vomiting  1  4/6 (66.67%)  4/11 (36.36%)  5/6 (83.33%)  0/4 (0.00%)  1/7 (14.29%)  4/5 (80.00%)  1/6 (16.67%) 
General disorders               
Adverse drug reaction  1  0/6 (0.00%)  1/11 (9.09%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Chest discomfort  1  0/6 (0.00%)  0/11 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Chest pain  1  0/6 (0.00%)  0/11 (0.00%)  0/6 (0.00%)  1/4 (25.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Chills  1  0/6 (0.00%)  1/11 (9.09%)  2/6 (33.33%)  1/4 (25.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Early satiety  1  0/6 (0.00%)  0/11 (0.00%)  0/6 (0.00%)  1/4 (25.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Fatigue  1  5/6 (83.33%)  8/11 (72.73%)  4/6 (66.67%)  2/4 (50.00%)  6/7 (85.71%)  5/5 (100.00%)  5/6 (83.33%) 
Hypothermia  1  0/6 (0.00%)  0/11 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Infusion site pain  1  0/6 (0.00%)  1/11 (9.09%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Irritability  1  0/6 (0.00%)  0/11 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Localised oedema  1  0/6 (0.00%)  0/11 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  1/5 (20.00%)  0/6 (0.00%) 
Mucosal inflammation  1  0/6 (0.00%)  2/11 (18.18%)  1/6 (16.67%)  0/4 (0.00%)  2/7 (28.57%)  0/5 (0.00%)  0/6 (0.00%) 
Non-cardiac chest pain  1  2/6 (33.33%)  0/11 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  1/5 (20.00%)  0/6 (0.00%) 
Oedema  1  1/6 (16.67%)  1/11 (9.09%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Oedema peripheral  1  0/6 (0.00%)  0/11 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  1/5 (20.00%)  0/6 (0.00%) 
Pain  1  0/6 (0.00%)  1/11 (9.09%)  0/6 (0.00%)  1/4 (25.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Pyrexia  1  1/6 (16.67%)  1/11 (9.09%)  2/6 (33.33%)  0/4 (0.00%)  0/7 (0.00%)  3/5 (60.00%)  1/6 (16.67%) 
Temperature intolerance  1  0/6 (0.00%)  0/11 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  1/7 (14.29%)  0/5 (0.00%)  0/6 (0.00%) 
Hepatobiliary disorders               
Cholecystitis  1  0/6 (0.00%)  0/11 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Immune system disorders               
Hypersensitivity  1  0/6 (0.00%)  0/11 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  1/6 (16.67%) 
Infections and infestations               
Candidiasis  1  1/6 (16.67%)  0/11 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  1/7 (14.29%)  0/5 (0.00%)  0/6 (0.00%) 
Cystitis  1  0/6 (0.00%)  0/11 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Escherichia bacteraemia  1  0/6 (0.00%)  0/11 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Eye infection  1  0/6 (0.00%)  0/11 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  1/7 (14.29%)  0/5 (0.00%)  0/6 (0.00%) 
Folliculitis  1  0/6 (0.00%)  1/11 (9.09%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Fungal infection  1  0/6 (0.00%)  0/11 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Gastroenteritis  1  1/6 (16.67%)  0/11 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Herpes simplex  1  0/6 (0.00%)  0/11 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Infected cyst  1  0/6 (0.00%)  0/11 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  1/6 (16.67%) 
Infection  1  1/6 (16.67%)  0/11 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Liver abscess  1  0/6 (0.00%)  0/11 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Lymph gland infection  1  0/6 (0.00%)  1/11 (9.09%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Oral candidiasis  1  0/6 (0.00%)  2/11 (18.18%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Oral infection  1  1/6 (16.67%)  0/11 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Paronychia  1  0/6 (0.00%)  0/11 (0.00%)  0/6 (0.00%)  1/4 (25.00%)  1/7 (14.29%)  1/5 (20.00%)  0/6 (0.00%) 
Respiratory tract infection  1  0/6 (0.00%)  1/11 (9.09%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Rhinitis  1  0/6 (0.00%)  0/11 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  1/5 (20.00%)  0/6 (0.00%) 
Sinusitis  1  3/6 (50.00%)  0/11 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Staphylococcal infection  1  0/6 (0.00%)  0/11 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  1/5 (20.00%)  0/6 (0.00%) 
Subcutaneous abscess  1  0/6 (0.00%)  0/11 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  1/7 (14.29%)  0/5 (0.00%)  0/6 (0.00%) 
Tooth abscess  1  0/6 (0.00%)  1/11 (9.09%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Tooth infection  1  0/6 (0.00%)  1/11 (9.09%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Upper respiratory tract infection  1  1/6 (16.67%)  0/11 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  1/7 (14.29%)  0/5 (0.00%)  0/6 (0.00%) 
Urinary tract infection  1  0/6 (0.00%)  1/11 (9.09%)  1/6 (16.67%)  0/4 (0.00%)  2/7 (28.57%)  0/5 (0.00%)  1/6 (16.67%) 
Injury, poisoning and procedural complications               
Incision site complication  1  0/6 (0.00%)  0/11 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  1/5 (20.00%)  0/6 (0.00%) 
Investigations               
Blood creatinine increased  1  0/6 (0.00%)  0/11 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  1/5 (20.00%)  0/6 (0.00%) 
Breath sounds abnormal  1  0/6 (0.00%)  1/11 (9.09%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Haemoglobin decreased  1  0/6 (0.00%)  0/11 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Weight decreased  1  1/6 (16.67%)  4/11 (36.36%)  2/6 (33.33%)  1/4 (25.00%)  2/7 (28.57%)  2/5 (40.00%)  2/6 (33.33%) 
White blood cell count decreased  1  0/6 (0.00%)  1/11 (9.09%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Metabolism and nutrition disorders               
Anorexia  1  0/6 (0.00%)  2/11 (18.18%)  3/6 (50.00%)  1/4 (25.00%)  4/7 (57.14%)  2/5 (40.00%)  1/6 (16.67%) 
Decreased appetite  1  1/6 (16.67%)  1/11 (9.09%)  0/6 (0.00%)  1/4 (25.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Dehydration  1  1/6 (16.67%)  1/11 (9.09%)  2/6 (33.33%)  0/4 (0.00%)  2/7 (28.57%)  0/5 (0.00%)  0/6 (0.00%) 
Hypercalcaemia  1  0/6 (0.00%)  0/11 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Hyperkalaemia  1  0/6 (0.00%)  0/11 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Hypoalbuminaemia  1  0/6 (0.00%)  0/11 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Hypocalcaemia  1  0/6 (0.00%)  0/11 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Hypokalaemia  1  0/6 (0.00%)  4/11 (36.36%)  3/6 (50.00%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  1/6 (16.67%) 
Hypomagnesaemia  1  1/6 (16.67%)  5/11 (45.45%)  5/6 (83.33%)  2/4 (50.00%)  3/7 (42.86%)  4/5 (80.00%)  2/6 (33.33%) 
Hyponatraemia  1  0/6 (0.00%)  0/11 (0.00%)  3/6 (50.00%)  0/4 (0.00%)  0/7 (0.00%)  1/5 (20.00%)  0/6 (0.00%) 
Hypophosphataemia  1  0/6 (0.00%)  0/11 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Musculoskeletal and connective tissue disorders               
Arthralgia  1  0/6 (0.00%)  3/11 (27.27%)  3/6 (50.00%)  0/4 (0.00%)  2/7 (28.57%)  1/5 (20.00%)  3/6 (50.00%) 
Back pain  1  1/6 (16.67%)  0/11 (0.00%)  2/6 (33.33%)  1/4 (25.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Muscle spasms  1  0/6 (0.00%)  0/11 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Muscular weakness  1  0/6 (0.00%)  0/11 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  1/5 (20.00%)  0/6 (0.00%) 
Musculoskeletal chest pain  1  0/6 (0.00%)  0/11 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  1/7 (14.29%)  0/5 (0.00%)  0/6 (0.00%) 
Musculoskeletal pain  1  0/6 (0.00%)  0/11 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  1/5 (20.00%)  0/6 (0.00%) 
Myalgia  1  2/6 (33.33%)  6/11 (54.55%)  1/6 (16.67%)  0/4 (0.00%)  4/7 (57.14%)  0/5 (0.00%)  2/6 (33.33%) 
Neck pain  1  0/6 (0.00%)  0/11 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  1/7 (14.29%)  0/5 (0.00%)  0/6 (0.00%) 
Pain in extremity  1  1/6 (16.67%)  0/11 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  4/6 (66.67%) 
Shoulder pain  1  1/6 (16.67%)  0/11 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  2/7 (28.57%)  0/5 (0.00%)  0/6 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)               
Metastases to central nervous system  1  0/6 (0.00%)  0/11 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Nervous system disorders               
Balance disorder  1  0/6 (0.00%)  1/11 (9.09%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  1/5 (20.00%)  0/6 (0.00%) 
Cognitive disorder  1  0/6 (0.00%)  1/11 (9.09%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  1/5 (20.00%)  0/6 (0.00%) 
Coordination abnormal  1  0/6 (0.00%)  0/11 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  1/6 (16.67%) 
Dizziness  1  2/6 (33.33%)  1/11 (9.09%)  2/6 (33.33%)  0/4 (0.00%)  1/7 (14.29%)  1/5 (20.00%)  0/6 (0.00%) 
Dysarthria  1  0/6 (0.00%)  0/11 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  1/5 (20.00%)  0/6 (0.00%) 
Dysgeusia  1  0/6 (0.00%)  1/11 (9.09%)  1/6 (16.67%)  0/4 (0.00%)  1/7 (14.29%)  1/5 (20.00%)  0/6 (0.00%) 
Headache  1  1/6 (16.67%)  4/11 (36.36%)  3/6 (50.00%)  0/4 (0.00%)  2/7 (28.57%)  0/5 (0.00%)  1/6 (16.67%) 
Hypoaesthesia  1  0/6 (0.00%)  2/11 (18.18%)  1/6 (16.67%)  0/4 (0.00%)  1/7 (14.29%)  1/5 (20.00%)  0/6 (0.00%) 
Memory impairment  1  0/6 (0.00%)  0/11 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  2/5 (40.00%)  0/6 (0.00%) 
Mental impairment  1  0/6 (0.00%)  0/11 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Neuropathy  1  4/6 (66.67%)  3/11 (27.27%)  2/6 (33.33%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  3/6 (50.00%) 
Neuropathy peripheral  1  1/6 (16.67%)  2/11 (18.18%)  1/6 (16.67%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Paraesthesia  1  1/6 (16.67%)  3/11 (27.27%)  1/6 (16.67%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Peripheral sensory neuropathy  1  0/6 (0.00%)  1/11 (9.09%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  1/5 (20.00%)  0/6 (0.00%) 
Restless legs syndrome  1  0/6 (0.00%)  0/11 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  1/6 (16.67%) 
Speech disorder  1  0/6 (0.00%)  1/11 (9.09%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Tremor  1  1/6 (16.67%)  0/11 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  1/6 (16.67%) 
Psychiatric disorders               
Anxiety  1  0/6 (0.00%)  2/11 (18.18%)  1/6 (16.67%)  1/4 (25.00%)  0/7 (0.00%)  1/5 (20.00%)  1/6 (16.67%) 
Confusional state  1  1/6 (16.67%)  1/11 (9.09%)  1/6 (16.67%)  0/4 (0.00%)  0/7 (0.00%)  1/5 (20.00%)  0/6 (0.00%) 
Depression  1  0/6 (0.00%)  0/11 (0.00%)  1/6 (16.67%)  1/4 (25.00%)  0/7 (0.00%)  0/5 (0.00%)  1/6 (16.67%) 
Insomnia  1  1/6 (16.67%)  1/11 (9.09%)  0/6 (0.00%)  1/4 (25.00%)  1/7 (14.29%)  0/5 (0.00%)  0/6 (0.00%) 
Mental status changes  1  1/6 (16.67%)  0/11 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Personality change  1  1/6 (16.67%)  1/11 (9.09%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Renal and urinary disorders               
Bladder pain  1  0/6 (0.00%)  0/11 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Haematuria  1  0/6 (0.00%)  0/11 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  1/6 (16.67%) 
Haemorrhage urinary tract  1  0/6 (0.00%)  0/11 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Incontinence  1  0/6 (0.00%)  0/11 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Micturition urgency  1  0/6 (0.00%)  0/11 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/7 (0.00%)  1/5 (20.00%)  0/6 (0.00%) 
Pollakiuria  1  0/6 (0.00%)  0/11 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  1/5 (20.00%)  0/6 (0.00%) 
Proteinuria  1  0/6 (0.00%)  0/11 (0.00%)  0/6 (0.00%)  1/4 (25.00%)  0/7 (0.00%)  1/5 (20.00%)  0/6 (0.00%) 
Reproductive system and breast disorders               
Pelvic discomfort  1  0/6 (0.00%)  1/11 (9.09%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Respiratory, thoracic and mediastinal disorders               
Allergic cough  1  0/6 (0.00%)  0/11 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  1/6 (16.67%) 
Cough  1  1/6 (16.67%)  3/11 (27.27%)  2/6 (33.33%)  1/4 (25.00%)  2/7 (28.57%)  1/5 (20.00%)  0/6 (0.00%) 
Dysphonia  1  2/6 (33.33%)  3/11 (27.27%)  1/6 (16.67%)  1/4 (25.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Dyspnoea  1  4/6 (66.67%)  4/11 (36.36%)  2/6 (33.33%)  0/4 (0.00%)  3/7 (42.86%)  0/5 (0.00%)  2/6 (33.33%) 
Dyspnoea exacerbated  1  0/6 (0.00%)  0/11 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  2/7 (28.57%)  0/5 (0.00%)  1/6 (16.67%) 
Epistaxis  1  0/6 (0.00%)  0/11 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  4/7 (57.14%)  1/5 (20.00%)  2/6 (33.33%) 
Haemoptysis  1  0/6 (0.00%)  0/11 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/7 (0.00%)  1/5 (20.00%)  0/6 (0.00%) 
Hiccups  1  1/6 (16.67%)  1/11 (9.09%)  1/6 (16.67%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Hypoxia  1  0/6 (0.00%)  1/11 (9.09%)  0/6 (0.00%)  0/4 (0.00%)  2/7 (28.57%)  0/5 (0.00%)  0/6 (0.00%) 
Pharyngolaryngeal pain  1  1/6 (16.67%)  1/11 (9.09%)  0/6 (0.00%)  0/4 (0.00%)  1/7 (14.29%)  1/5 (20.00%)  0/6 (0.00%) 
Pleural rub  1  1/6 (16.67%)  0/11 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Pleuritic pain  1  0/6 (0.00%)  1/11 (9.09%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Pulmonary embolism  1  1/6 (16.67%)  0/11 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  1/6 (16.67%) 
Pulmonary haemorrhage  1  0/6 (0.00%)  0/11 (0.00%)  0/6 (0.00%)  1/4 (25.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Rales  1  0/6 (0.00%)  2/11 (18.18%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Rhinitis allergic  1  0/6 (0.00%)  1/11 (9.09%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  1/6 (16.67%) 
Rhinorrhoea  1  1/6 (16.67%)  0/11 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Sinus congestion  1  0/6 (0.00%)  1/11 (9.09%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Skin and subcutaneous tissue disorders               
Acne  1  0/6 (0.00%)  0/11 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  2/7 (28.57%)  0/5 (0.00%)  0/6 (0.00%) 
Alopecia  1  2/6 (33.33%)  4/11 (36.36%)  1/6 (16.67%)  0/4 (0.00%)  2/7 (28.57%)  0/5 (0.00%)  4/6 (66.67%) 
Dermatitis  1  0/6 (0.00%)  0/11 (0.00%)  0/6 (0.00%)  1/4 (25.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Dermatitis acneiform  1  0/6 (0.00%)  1/11 (9.09%)  0/6 (0.00%)  1/4 (25.00%)  3/7 (42.86%)  3/5 (60.00%)  6/6 (100.00%) 
Dry skin  1  0/6 (0.00%)  0/11 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  3/7 (42.86%)  1/5 (20.00%)  1/6 (16.67%) 
Erythema  1  1/6 (16.67%)  1/11 (9.09%)  0/6 (0.00%)  2/4 (50.00%)  2/7 (28.57%)  0/5 (0.00%)  1/6 (16.67%) 
Exfoliative rash  1  0/6 (0.00%)  1/11 (9.09%)  1/6 (16.67%)  3/4 (75.00%)  3/7 (42.86%)  0/5 (0.00%)  0/6 (0.00%) 
Hyperhidrosis  1  0/6 (0.00%)  0/11 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  1/5 (20.00%)  0/6 (0.00%) 
Nail disorder  1  0/6 (0.00%)  0/11 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  1/7 (14.29%)  0/5 (0.00%)  0/6 (0.00%) 
Night sweats  1  0/6 (0.00%)  0/11 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Pain of skin  1  0/6 (0.00%)  0/11 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  1/7 (14.29%)  0/5 (0.00%)  0/6 (0.00%) 
Palmar erythema  1  0/6 (0.00%)  1/11 (9.09%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Pruritus  1  1/6 (16.67%)  2/11 (18.18%)  0/6 (0.00%)  0/4 (0.00%)  6/7 (85.71%)  3/5 (60.00%)  3/6 (50.00%) 
Rash  1  0/6 (0.00%)  3/11 (27.27%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  2/5 (40.00%)  0/6 (0.00%) 
Rash erythematous  1  0/6 (0.00%)  2/11 (18.18%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Rash follicular  1  1/6 (16.67%)  0/11 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Rash generalised  1  0/6 (0.00%)  0/11 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  1/7 (14.29%)  0/5 (0.00%)  0/6 (0.00%) 
Rash maculo-papular  1  0/6 (0.00%)  0/11 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  1/5 (20.00%)  0/6 (0.00%) 
Rash pruritic  1  0/6 (0.00%)  0/11 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  1/5 (20.00%)  0/6 (0.00%) 
Skin fissures  1  0/6 (0.00%)  0/11 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  2/7 (28.57%)  0/5 (0.00%)  0/6 (0.00%) 
Skin lesion  1  1/6 (16.67%)  0/11 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Skin ulcer  1  0/6 (0.00%)  0/11 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  1/7 (14.29%)  0/5 (0.00%)  0/6 (0.00%) 
Vascular disorders               
Deep vein thrombosis  1  0/6 (0.00%)  1/11 (9.09%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  1/6 (16.67%) 
Flushing  1  1/6 (16.67%)  1/11 (9.09%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Hot flush  1  0/6 (0.00%)  1/11 (9.09%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Hypertension  1  4/6 (66.67%)  5/11 (45.45%)  4/6 (66.67%)  1/4 (25.00%)  4/7 (57.14%)  3/5 (60.00%)  3/6 (50.00%) 
Hypotension  1  3/6 (50.00%)  3/11 (27.27%)  2/6 (33.33%)  0/4 (0.00%)  2/7 (28.57%)  0/5 (0.00%)  0/6 (0.00%) 
Orthostatic hypotension  1  0/6 (0.00%)  0/11 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  0/6 (0.00%) 
Phlebitis  1  0/6 (0.00%)  0/11 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  1/7 (14.29%)  0/5 (0.00%)  0/6 (0.00%) 
Thrombosis  1  1/6 (16.67%)  0/11 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/7 (0.00%)  0/5 (0.00%)  1/6 (16.67%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 9.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results aftercompletion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: Amgen Inc.
Phone: 866-572-6436
Layout table for additonal information
Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT00094835    
Obsolete Identifiers: NCT00107224
Other Study ID Numbers: 20040153
First Submitted: October 27, 2004
First Posted: October 27, 2004
Results First Submitted: August 13, 2010
Results First Posted: March 24, 2014
Last Update Posted: March 24, 2016