Trial Outcomes & Findings for A Randomized Controlled Trial Comparing Safety and Efficacy of Carboplatin and Paclitaxel Plus or Minus Sorafenib (BAY 43-9006) in Chemonaive Patients With Stage IIIB-IV Non-Small Cell Lung Cancer (NSCLC) (NCT NCT00300885)

NCT ID: NCT00300885

Last Updated: 2014-11-04

Results Overview

Overall survival determined as the time (days) from the date of randomization at start of study to the date of death, due to any cause. Outcome measure was assessed regularly, i.e. every 3 weeks during study treatment and every 3 months during post-treatment.

• Recruitment status: TERMINATED
• Study phase: PHASE3
• Target enrollment: 926 participants
• Primary outcome timeframe: Outcome measure was assessed every 3 weeks starting from randomization, during treatment period and every 3 months during follow-up period until death was recorded or up to data cutoff (1Oct2007) used for planned formal interim analysis
• Results posted on: 2014-11-04

Participant Flow

This study was conducted at 150 centers across 20 countries, which enrolled and randomized at least one subject. From a total of 1043 subjects who were screened, 926 subjects were randomized between 15 February 2006 and 9 May 2007 in 20 countries.

Of the 926 subjects who were randomized, 922 received at least one dose of study drug. All 926 subjects were included in the ITT population (intent-to-treat; defined as all randomized patients), all but four subjects did receive study drug. They were not included in the safety population.

Participant milestones

Measure	Sorafenib + C/P Chemotherapy Phase up to 6 cycles: Sorafenib (Nexavar, BAY43-9006), \[400 mg orally, twice daily\] on Study Days 2-19 and paclitaxel (P) (200 mg/m2, intravenous (IV)) and carboplatin (C) (area under the curve (AUC) =6 mg/ml\*min-1, IV) on Study Day 1. The cycle duration 21 days. Maintenance Phase: Sorafenib 400 mg orally twice daily was administered on Days 1-21 of each 21-day cycle.	Placebo + C/P Chemotherapy Phase up to 6 cycles: Sorafenib Placebo (2 tablets orally twice daily\] on Study Days 2-19 and paclitaxel (200 mg/m2, intravenous (IV)) and carboplatin (area under the curve (AUC) =6 mg/ml\*min-1, IV) on Study Day 1. The cycle duration 21 days. Maintenance Phase: Sorafenib Placebo 2 tablets orally twice daily was administered on Days 1-21 of each 21-day cycle.
Treatment STARTED	464	462
Treatment Received Treatment	463	459
Treatment COMPLETED	91	88
Treatment NOT COMPLETED	373	374
Follow-up STARTED	354	369
Follow-up COMPLETED	176	174
Follow-up NOT COMPLETED	178	195

Reasons for withdrawal

Measure	Sorafenib + C/P Chemotherapy Phase up to 6 cycles: Sorafenib (Nexavar, BAY43-9006), \[400 mg orally, twice daily\] on Study Days 2-19 and paclitaxel (P) (200 mg/m2, intravenous (IV)) and carboplatin (C) (area under the curve (AUC) =6 mg/ml\*min-1, IV) on Study Day 1. The cycle duration 21 days. Maintenance Phase: Sorafenib 400 mg orally twice daily was administered on Days 1-21 of each 21-day cycle.	Placebo + C/P Chemotherapy Phase up to 6 cycles: Sorafenib Placebo (2 tablets orally twice daily\] on Study Days 2-19 and paclitaxel (200 mg/m2, intravenous (IV)) and carboplatin (area under the curve (AUC) =6 mg/ml\*min-1, IV) on Study Day 1. The cycle duration 21 days. Maintenance Phase: Sorafenib Placebo 2 tablets orally twice daily was administered on Days 1-21 of each 21-day cycle.
Treatment Adverse Event	134	82
Treatment Death	20	7
Treatment Lack of Efficacy	1	1
Treatment Lost to Follow-up	3	2
Treatment Physician Decision	4	5
Treatment Protocol Violation	11	11
Treatment Withdrawal by Subject	26	23
Treatment Disease progression	171	238
Treatment Random code broken (subject died)	0	1
Treatment Non-compliant with study medication	3	4
Follow-up Death	141	163
Follow-up Lost to Follow-up	11	7
Follow-up Withdrawal by Subject	26	25

Baseline Characteristics

A Randomized Controlled Trial Comparing Safety and Efficacy of Carboplatin and Paclitaxel Plus or Minus Sorafenib (BAY 43-9006) in Chemonaive Patients With Stage IIIB-IV Non-Small Cell Lung Cancer (NSCLC)

Baseline characteristics by cohort

Measure	Sorafenib + C/P n=464 Participants Chemotherapy Phase up to 6 cycles: Sorafenib (Nexavar, BAY43-9006), \[400 mg orally, twice daily\] on Study Days 2-19 and paclitaxel (P) (200 mg/m2, intravenous (IV)) and carboplatin (C) (area under the curve (AUC) =6 mg/ml\*min-1, IV) on Study Day 1. The cycle duration 21 days. Maintenance Phase: Sorafenib 400 mg orally twice daily was administered on Days 1-21 of each 21-day cycle.	Placebo + C/P n=462 Participants Chemotherapy Phase up to 6 cycles: Sorafenib Placebo (2 tablets orally twice daily\] on Study Days 2-19 and paclitaxel (200 mg/m2, intravenous (IV)) and carboplatin (area under the curve (AUC) =6 mg/ml\*min-1, IV) on Study Day 1. The cycle duration 21 days. Maintenance Phase: Sorafenib Placebo 2 tablets orally twice daily was administered on Days 1-21 of each 21-day cycle.	Total n=926 Participants Total of all reporting groups
Age, Continuous	62 years n=5 Participants	63 years n=7 Participants	62 years n=5 Participants
Sex: Female, Male Female	171 Participants n=5 Participants	174 Participants n=7 Participants	345 Participants n=5 Participants
Sex: Female, Male Male	293 Participants n=5 Participants	288 Participants n=7 Participants	581 Participants n=5 Participants
ECOG (Eastern Cooperative Oncology Group) Performance Status 0	190 Participants n=5 Participants	188 Participants n=7 Participants	378 Participants n=5 Participants
ECOG (Eastern Cooperative Oncology Group) Performance Status 1	274 Participants n=5 Participants	274 Participants n=7 Participants	548 Participants n=5 Participants
Geographic region core	325 Participants n=5 Participants	323 Participants n=7 Participants	648 Participants n=5 Participants
Geographic region non-core	139 Participants n=5 Participants	139 Participants n=7 Participants	278 Participants n=5 Participants
NSCLC Classification Adenocarcinoma NSCLC	263 Participants n=5 Participants	271 Participants n=7 Participants	534 Participants n=5 Participants
NSCLC Classification Bronchoalveolar	6 Participants n=5 Participants	5 Participants n=7 Participants	11 Participants n=5 Participants
NSCLC Classification Non-Microcellulare carcinoma	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
NSCLC Classification Large cell carcinoma	23 Participants n=5 Participants	30 Participants n=7 Participants	53 Participants n=5 Participants
NSCLC Classification Squamous cell carcinoma	109 Participants n=5 Participants	114 Participants n=7 Participants	223 Participants n=5 Participants
NSCLC Classification Non-Small cell lung cancer carcinoma	10 Participants n=5 Participants	10 Participants n=7 Participants	20 Participants n=5 Participants
NSCLC Classification Undifferentiated carcinoma	46 Participants n=5 Participants	26 Participants n=7 Participants	72 Participants n=5 Participants
NSCLC Classification Poorly differentiated non-small cell carcinoma	4 Participants n=5 Participants	3 Participants n=7 Participants	7 Participants n=5 Participants
NSCLC Classification Neuro-Endocrine carcinoma	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
NSCLC Classification Low differentiated carcinoma (neuro-endocrine)	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
NSCLC Classification Unknown or unspecified histology	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Stage at Study Entry Stage III B	44 Participants n=5 Participants	47 Participants n=7 Participants	91 Participants n=5 Participants
Stage at Study Entry Stage IV	420 Participants n=5 Participants	415 Participants n=7 Participants	835 Participants n=5 Participants

PRIMARY outcome

Timeframe: Outcome measure was assessed every 3 weeks starting from randomization, during treatment period and every 3 months during follow-up period until death was recorded or up to data cutoff (1Oct2007) used for planned formal interim analysis

Population: Evaluations of OS based on the ITT population. Subjects alive at the time of analysis were censored at their last date of follow-up (last visit or contact or at the data cut-off date). In the case of an incomplete date, if the day is missing, day 15 (the middle of the month) will be used.

Overall survival determined as the time (days) from the date of randomization at start of study to the date of death, due to any cause. Outcome measure was assessed regularly, i.e. every 3 weeks during study treatment and every 3 months during post-treatment.

Outcome measures

Measure	Sorafenib + C/P n=464 Participants Chemotherapy Phase up to 6 cycles: Sorafenib (Nexavar, BAY43-9006), \[400 mg orally, twice daily\] on Study Days 2-19 and paclitaxel (P) (200 mg/m2, intravenous (IV)) and carboplatin (C) (area under the curve (AUC) =6 mg/ml\*min-1, IV) on Study Day 1. The cycle duration 21 days. Maintenance Phase: Sorafenib 400 mg orally twice daily was administered on Days 1-21 of each 21-day cycle.	Placebo + C/P n=462 Participants Chemotherapy Phase up to 6 cycles: Sorafenib Placebo (2 tablets orally twice daily\] on Study Days 2-19 and paclitaxel (200 mg/m2, intravenous (IV)) and carboplatin (area under the curve (AUC) =6 mg/ml\*min-1, IV) on Study Day 1. The cycle duration 21 days. Maintenance Phase: Sorafenib Placebo 2 tablets orally twice daily was administered on Days 1-21 of each 21-day cycle.
Overall Survival (OS) in Patients Treated With Carboplatin, Paclitaxel and Sorafenib to OS in Patients Treated With Carboplatin, Paclitaxel and Placebo	324 days Interval 277.0 to 423.0	322 days Interval 293.0 to 366.0

SECONDARY outcome

Timeframe: Tumor measurements and assessments based on RECIST criteria were performed every 6 weeks for the first 18 weeks of therapy ( week 6, 12, and 18) and every 12 weeks thereafter up to data cutoff (1Oct2007) used for planned formal interim analysis

Population: PFS (based on the ITT population) for subjects without disease progression/death at the time of analysis were censored at the last evaluation date. PFS for surviving subjects without post-baseline tumor assessments were censored at one day. In the case of an incomplete date (missing day), day 15 (the middle of the month) will be used.

PFS determined as time (days) from the date of randomization at start of study to disease progression (radiological or clinical) or death due to any cause, if death occurs before progression.

Outcome measures

Measure	Sorafenib + C/P n=464 Participants Chemotherapy Phase up to 6 cycles: Sorafenib (Nexavar, BAY43-9006), \[400 mg orally, twice daily\] on Study Days 2-19 and paclitaxel (P) (200 mg/m2, intravenous (IV)) and carboplatin (C) (area under the curve (AUC) =6 mg/ml\*min-1, IV) on Study Day 1. The cycle duration 21 days. Maintenance Phase: Sorafenib 400 mg orally twice daily was administered on Days 1-21 of each 21-day cycle.	Placebo + C/P n=462 Participants Chemotherapy Phase up to 6 cycles: Sorafenib Placebo (2 tablets orally twice daily\] on Study Days 2-19 and paclitaxel (200 mg/m2, intravenous (IV)) and carboplatin (area under the curve (AUC) =6 mg/ml\*min-1, IV) on Study Day 1. The cycle duration 21 days. Maintenance Phase: Sorafenib Placebo 2 tablets orally twice daily was administered on Days 1-21 of each 21-day cycle.
Progression Free Survival (PFS)	139 days Interval 132.0 to 160.0	163 days Interval 134.0 to 175.0

SECONDARY outcome

Timeframe: Tumor measurements and assessments based on RECIST criteria were performed every 6 weeks for the first 18 weeks of therapy ( week 6, 12, and 18) and every 12 weeks thereafter up to data cutoff (1Oct2007) used for planned formal interim analysis

Population: Evaluations of overall best response rate based on the ITT population.

Best overall tumor response for the ITT population was determined according to Response Evaluation Criteria in Solid Tumors (RECIST). Categories: complete response (CR, tumor disappears), partial response (PR, sum of lesion sizes decreased), stable disease (SD, steady state of disease), progressive disease (PD, sum of lesion sizes increased).

Outcome measures

Measure	Sorafenib + C/P n=464 Participants Chemotherapy Phase up to 6 cycles: Sorafenib (Nexavar, BAY43-9006), \[400 mg orally, twice daily\] on Study Days 2-19 and paclitaxel (P) (200 mg/m2, intravenous (IV)) and carboplatin (C) (area under the curve (AUC) =6 mg/ml\*min-1, IV) on Study Day 1. The cycle duration 21 days. Maintenance Phase: Sorafenib 400 mg orally twice daily was administered on Days 1-21 of each 21-day cycle.	Placebo + C/P n=462 Participants Chemotherapy Phase up to 6 cycles: Sorafenib Placebo (2 tablets orally twice daily\] on Study Days 2-19 and paclitaxel (200 mg/m2, intravenous (IV)) and carboplatin (area under the curve (AUC) =6 mg/ml\*min-1, IV) on Study Day 1. The cycle duration 21 days. Maintenance Phase: Sorafenib Placebo 2 tablets orally twice daily was administered on Days 1-21 of each 21-day cycle.
Overall Best Response Complete Response (CR)	0.0 percentage of participants	1.1 percentage of participants
Overall Best Response Partial Response (PR)	27.4 percentage of participants	22.9 percentage of participants
Overall Best Response Stable Disease (SD)	45.9 percentage of participants	47.8 percentage of participants
Overall Best Response Progressive Disease (PD)	9.9 percentage of participants	17.5 percentage of participants
Overall Best Response Not evaluated	16.8 percentage of participants	10.6 percentage of participants
Overall Best Response Disease control	49.8 percentage of participants	56.3 percentage of participants

SECONDARY outcome

Timeframe: Tumor measurements and assessments based on RECIST criteria were performed every 6 weeks for the first 18 weeks of therapy ( week 6, 12, and 18) and every 12 weeks thereafter up to data cutoff (1Oct2007) used for planned formal interim analysis

Population: Evaluations of duration of response based on the ITT population.

Duration of response (PR or better) is defined as the time from the first documented objective response of PR or CR, whichever is noted earlier, to disease progression or death (if death occurs before progression is documented).

Outcome measures

Measure	Sorafenib + C/P n=127 Participants Chemotherapy Phase up to 6 cycles: Sorafenib (Nexavar, BAY43-9006), \[400 mg orally, twice daily\] on Study Days 2-19 and paclitaxel (P) (200 mg/m2, intravenous (IV)) and carboplatin (C) (area under the curve (AUC) =6 mg/ml\*min-1, IV) on Study Day 1. The cycle duration 21 days. Maintenance Phase: Sorafenib 400 mg orally twice daily was administered on Days 1-21 of each 21-day cycle.	Placebo + C/P n=111 Participants Chemotherapy Phase up to 6 cycles: Sorafenib Placebo (2 tablets orally twice daily\] on Study Days 2-19 and paclitaxel (200 mg/m2, intravenous (IV)) and carboplatin (area under the curve (AUC) =6 mg/ml\*min-1, IV) on Study Day 1. The cycle duration 21 days. Maintenance Phase: Sorafenib Placebo 2 tablets orally twice daily was administered on Days 1-21 of each 21-day cycle.
Duration of Response	168 days Interval 142.0 to 184.0	134 days Interval 126.0 to 165.0

SECONDARY outcome

Timeframe: Outcome measure was assessed on Day 1 of Cycle 1 and Day 1 of every other cycle (i.e. Cycle 3, 5, 7 etc.) during treatment and at end of treatment visit or up to data cutoff (10ct2007) used for planned formal interim analysis

Population: Evaluations of Total FACT-L based on the ITT population.

Functional Assessment of Cancer Therapy - Lung cancer subscore (FACT-L). Patient reported outcome as assessed by FACT-L score. FACT-L questionnaire comprises statements about physical, social / family, emotional and functional well-being as well as additional concerns which have to be rated by the patients (0="not at all" to 4="very much"). Cycle duration defined as 21 days. Change from baseline in Total FACT-L on day 1 of cycles 3,5,7,9 (weeks 7,13,19 and 25) and end of treatment (EOT); cycle 1, day 1 used as baseline. EOT is determined by patient's last visit after treatment discontinuation.

Outcome measures

Measure	Sorafenib + C/P n=464 Participants Chemotherapy Phase up to 6 cycles: Sorafenib (Nexavar, BAY43-9006), \[400 mg orally, twice daily\] on Study Days 2-19 and paclitaxel (P) (200 mg/m2, intravenous (IV)) and carboplatin (C) (area under the curve (AUC) =6 mg/ml\*min-1, IV) on Study Day 1. The cycle duration 21 days. Maintenance Phase: Sorafenib 400 mg orally twice daily was administered on Days 1-21 of each 21-day cycle.	Placebo + C/P n=462 Participants Chemotherapy Phase up to 6 cycles: Sorafenib Placebo (2 tablets orally twice daily\] on Study Days 2-19 and paclitaxel (200 mg/m2, intravenous (IV)) and carboplatin (area under the curve (AUC) =6 mg/ml\*min-1, IV) on Study Day 1. The cycle duration 21 days. Maintenance Phase: Sorafenib Placebo 2 tablets orally twice daily was administered on Days 1-21 of each 21-day cycle.
Patient Reported Outcome as Assessed by FACT-L Score. Change From Baseline in Total FACT-L at Cycles 3,5,7,9 and End of Treatment (EOT) Cycle 3, Day 1	0.0 Scores on a scale Standard Deviation 8.0	0.1 Scores on a scale Standard Deviation 9.7
Patient Reported Outcome as Assessed by FACT-L Score. Change From Baseline in Total FACT-L at Cycles 3,5,7,9 and End of Treatment (EOT) Cycle 5, Day 1	-1.4 Scores on a scale Standard Deviation 10.5	-1.3 Scores on a scale Standard Deviation 9.8
Patient Reported Outcome as Assessed by FACT-L Score. Change From Baseline in Total FACT-L at Cycles 3,5,7,9 and End of Treatment (EOT) Cycle 7, Day 1	-0.8 Scores on a scale Standard Deviation 8.1	-0.5 Scores on a scale Standard Deviation 9.4
Patient Reported Outcome as Assessed by FACT-L Score. Change From Baseline in Total FACT-L at Cycles 3,5,7,9 and End of Treatment (EOT) Cycle 9, Day 1	-1.2 Scores on a scale Standard Deviation 8.0	-0.6 Scores on a scale Standard Deviation 10.6
Patient Reported Outcome as Assessed by FACT-L Score. Change From Baseline in Total FACT-L at Cycles 3,5,7,9 and End of Treatment (EOT) End of treatment (EOT)	-3.1 Scores on a scale Standard Deviation 10.6	-2.7 Scores on a scale Standard Deviation 10.5

SECONDARY outcome

Timeframe: Outcome measure was assessed on Day 1 of Cycle 1 and Day 1 of every cycle (i.e. Cycle 2, 3, 4, 5 etc.) during treatment and at end of treatment visit or up to data cutoff (10ct2007) used for planned formal interim analysis

Population: Evaluations of LCS Subscale based on the ITT population.

Lung Cancer Symptoms (LCS) subscale ranges from 0 (severe debilitation) to 28 (asymptomatic). Cycle duration defined as 21 days. Change from baseline in LCS Subscale on day 1 of cycles 2 through 9 (weeks 4,7,10,13,16,19,22 and 25) and end of treatment (EOT); cycle 1, day 1 used as baseline. EOT is determined by patient's last visit after treatment discontinuation.

Outcome measures

Measure	Sorafenib + C/P n=464 Participants Chemotherapy Phase up to 6 cycles: Sorafenib (Nexavar, BAY43-9006), \[400 mg orally, twice daily\] on Study Days 2-19 and paclitaxel (P) (200 mg/m2, intravenous (IV)) and carboplatin (C) (area under the curve (AUC) =6 mg/ml\*min-1, IV) on Study Day 1. The cycle duration 21 days. Maintenance Phase: Sorafenib 400 mg orally twice daily was administered on Days 1-21 of each 21-day cycle.	Placebo + C/P n=462 Participants Chemotherapy Phase up to 6 cycles: Sorafenib Placebo (2 tablets orally twice daily\] on Study Days 2-19 and paclitaxel (200 mg/m2, intravenous (IV)) and carboplatin (area under the curve (AUC) =6 mg/ml\*min-1, IV) on Study Day 1. The cycle duration 21 days. Maintenance Phase: Sorafenib Placebo 2 tablets orally twice daily was administered on Days 1-21 of each 21-day cycle.
Patient Reported Outcome as Assessed by LCS Subscale Score. Change From Baseline in LCS Subscale at Cycles 2 Through 9 and at End of Treatment (EOT) Cycle 6, Day 1	-0.8 Scores on a scale Standard Deviation 2.9	-0.4 Scores on a scale Standard Deviation 3.1
Patient Reported Outcome as Assessed by LCS Subscale Score. Change From Baseline in LCS Subscale at Cycles 2 Through 9 and at End of Treatment (EOT) Cycle 2, Day 1	0.0 Scores on a scale Standard Deviation 2.7	-0.1 Scores on a scale Standard Deviation 3.1
Patient Reported Outcome as Assessed by LCS Subscale Score. Change From Baseline in LCS Subscale at Cycles 2 Through 9 and at End of Treatment (EOT) Cycle 3, Day 1	-0.4 Scores on a scale Standard Deviation 2.9	-0.2 Scores on a scale Standard Deviation 2.9
Patient Reported Outcome as Assessed by LCS Subscale Score. Change From Baseline in LCS Subscale at Cycles 2 Through 9 and at End of Treatment (EOT) Cycle 4, Day 1	-0.6 Scores on a scale Standard Deviation 2.9	-0.3 Scores on a scale Standard Deviation 3.0
Patient Reported Outcome as Assessed by LCS Subscale Score. Change From Baseline in LCS Subscale at Cycles 2 Through 9 and at End of Treatment (EOT) Cycle 5, Day 1	-0.6 Scores on a scale Standard Deviation 2.9	-0.5 Scores on a scale Standard Deviation 2.9
Patient Reported Outcome as Assessed by LCS Subscale Score. Change From Baseline in LCS Subscale at Cycles 2 Through 9 and at End of Treatment (EOT) Cycle 7, Day 1	-0.8 Scores on a scale Standard Deviation 3.1	-0.4 Scores on a scale Standard Deviation 2.9
Patient Reported Outcome as Assessed by LCS Subscale Score. Change From Baseline in LCS Subscale at Cycles 2 Through 9 and at End of Treatment (EOT) Cycle 8, Day 1	-1.2 Scores on a scale Standard Deviation 3.2	-0.2 Scores on a scale Standard Deviation 2.6
Patient Reported Outcome as Assessed by LCS Subscale Score. Change From Baseline in LCS Subscale at Cycles 2 Through 9 and at End of Treatment (EOT) Cycle 9, Day 1	-0.9 Scores on a scale Standard Deviation 3.1	-0.3 Scores on a scale Standard Deviation 3.3
Patient Reported Outcome as Assessed by LCS Subscale Score. Change From Baseline in LCS Subscale at Cycles 2 Through 9 and at End of Treatment (EOT) End of treatment (EOT)	-0.9 Scores on a scale Standard Deviation 3.2	-0.4 Scores on a scale Standard Deviation 3.0

Adverse Events

Sorafenib + C/P

Serious events: 272 serious events

Other events: 454 other events

Deaths: 0 deaths

Placebo + C/P

Serious events: 195 serious events

Other events: 450 other events

Deaths: 0 deaths

Serious adverse events

Measure	Sorafenib + C/P n=463 participants at risk Chemotherapy Phase up to 6 cycles: Sorafenib (Nexavar, BAY43-9006), \[400 mg orally, twice daily\] on Study Days 2-19 and paclitaxel (P) (200 mg/m2, intravenous (IV)) and carboplatin (C) (area under the curve (AUC) =6 mg/ml\*min-1, IV) on Study Day 1. The cycle duration 21 days. Maintenance Phase: Sorafenib 400 mg orally twice daily was administered on Days 1-21 of each 21-day cycle.	Placebo + C/P n=459 participants at risk Chemotherapy Phase up to 6 cycles: Sorafenib Placebo (2 tablets orally twice daily\] on Study Days 2-19 and paclitaxel (200 mg/m2, intravenous (IV)) and carboplatin (area under the curve (AUC) =6 mg/ml\*min-1, IV) on Study Day 1. The cycle duration 21 days. Maintenance Phase: Sorafenib Placebo 2 tablets orally twice daily was administered on Days 1-21 of each 21-day cycle.
Nervous system disorders Somnolence	0.43% 2/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.00% 0/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Immune system disorders Allergic reaction	2.4% 11/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.87% 4/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Blood and lymphatic system disorders Neutrophils	3.2% 15/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	1.5% 7/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Blood and lymphatic system disorders Hemoglobin	2.4% 11/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	1.7% 8/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Blood and lymphatic system disorders Hemolysis	0.22% 1/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.00% 0/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Blood and lymphatic system disorders Platelets	1.7% 8/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.44% 2/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Blood and lymphatic system disorders Leukocytes	0.43% 2/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.22% 1/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Cardiac disorders Supraventricular arrhythmia, atrial fibrillation	0.43% 2/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.22% 1/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Cardiac disorders Conduction abnormality, asystole	0.22% 1/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.00% 0/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Cardiac disorders Supraventricular arrhythmia, sinus bradycardia	0.22% 1/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.00% 0/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Cardiac disorders Supraventricular arrhythmia, supravent extrasystoles (pac;premnodal/junct contr)	0.22% 1/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.00% 0/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Cardiac disorders Supraventricular arrhythmia, supraventricular tachycardia	0.65% 3/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.00% 0/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Cardiac disorders Supraventricular arrhythmia, sinus tachycardia	0.43% 2/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.00% 0/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Cardiac disorders vasovagal episode	0.00% 0/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.22% 1/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Cardiac disorders Ventricular arrhythmia, ventricular fibrillation	0.00% 0/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.22% 1/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Cardiac disorders Ventricular arrhythmia, ventricular arrhythmia NOS	0.00% 0/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.22% 1/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Cardiac disorders Ventricular arrhythmia, ventricular tachycardia	0.00% 0/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.22% 1/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Cardiac disorders Cardiopulmonary arrest	0.65% 3/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.44% 2/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Cardiac disorders Pericardial effusion	0.00% 0/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.65% 3/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Cardiac disorders Hypertension	0.43% 2/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.44% 2/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Cardiac disorders Cardiac ischemia/infarction	0.65% 3/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.87% 4/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Cardiac disorders Hypotension	0.22% 1/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.22% 1/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Cardiac disorders Left ventricular systolic dysfunction	0.22% 1/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.00% 0/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
General disorders Death not associated with CTCAE term, death NOS	0.86% 4/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.44% 2/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
General disorders Death not associated with CTCAE term, disease progression NOS	5.0% 23/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	5.2% 24/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
General disorders Death not associated with CTCAE term, multi-organ failure	0.00% 0/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.22% 1/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
General disorders Death not associated with CTCAE term, sudden death	0.65% 3/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.22% 1/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Endocrine disorders Diabetes	0.22% 1/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.00% 0/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
General disorders Fever	3.7% 17/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	2.2% 10/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
General disorders Fatigue	1.1% 5/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.87% 4/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
General disorders Weight loss	0.22% 1/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.00% 0/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
General disorders Constitutional symptoms - other	4.1% 19/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	2.8% 13/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
General disorders Rigors/chills	0.22% 1/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.00% 0/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Gastrointestinal disorders Anorexia	0.65% 3/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.44% 2/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Gastrointestinal disorders Colitis	0.22% 1/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.22% 1/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Gastrointestinal disorders Constipation	0.43% 2/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.22% 1/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Gastrointestinal disorders Dehydration	1.9% 9/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.87% 4/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Gastrointestinal disorders Diarrhea	1.1% 5/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	1.3% 6/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Gastrointestinal disorders Dysphagia	0.22% 1/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.44% 2/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Gastrointestinal disorders Enteritis	0.00% 0/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.22% 1/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Gastrointestinal disorders Gastritis	0.22% 1/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.22% 1/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Gastrointestinal disorders Mucositis (clinical exam), oral cavity	0.22% 1/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.00% 0/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Gastrointestinal disorders Necrosis, GI, anus	0.22% 1/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.00% 0/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Gastrointestinal disorders Nausea	1.1% 5/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	1.1% 5/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Gastrointestinal disorders Ileus	0.43% 2/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.44% 2/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Gastrointestinal disorders Perforation, GI, colon	0.22% 1/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.00% 0/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Gastrointestinal disorders Ulcer, GI, stomach	0.00% 0/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.22% 1/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Gastrointestinal disorders Vomiting	0.65% 3/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.44% 2/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Vascular disorders Hemorrhage, GI, abdomen NOS	0.43% 2/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.00% 0/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Vascular disorders Hemorrhage, GI, colon	0.00% 0/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.44% 2/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Vascular disorders Hemorrhage, GI, duodenum	0.22% 1/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.00% 0/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Vascular disorders Hemorrhage, GI, stomach	0.00% 0/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.22% 1/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Vascular disorders Hemorrhage, GI, lower GI NOS	0.22% 1/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.00% 0/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Vascular disorders Hemorrhage, GI, upper GI, NOS	0.00% 0/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.22% 1/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Vascular disorders Hemorrhage pulmonary, bronchopulmonary NOS	0.00% 0/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.44% 2/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Vascular disorders Hemorrhage pulmonary, bronchus	0.00% 0/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.22% 1/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Vascular disorders Hemorrhage pulmonary, lung	2.4% 11/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	1.7% 8/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Vascular disorders Hemorrhage pulmonary, nose	0.22% 1/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.00% 0/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Vascular disorders Hemorrhage pulmonary, respiratory tract NOS	1.1% 5/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.22% 1/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Hepatobiliary disorders Cholecystitis	0.22% 1/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.22% 1/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Hepatobiliary disorders Hepatobilary - other	0.00% 0/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.22% 1/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Hepatobiliary disorders Pancreatitis	0.22% 1/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.00% 0/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Infections and infestations Infection (documented clinically), abdomen NOS	0.22% 1/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.00% 0/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Infections and infestations Infection (documented clinically), blood	1.9% 9/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.00% 0/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Infections and infestations Infection (documented clinically), bladder (urinary)	0.00% 0/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.22% 1/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Infections and infestations Infection (documented clinically), bronchus	0.22% 1/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.65% 3/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Infections and infestations Infection (documented clinically), lung (pneumonia)	5.4% 25/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	2.2% 10/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Infections and infestations Infection (documented clinically), pleura (empyema)	0.00% 0/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.22% 1/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Infections and infestations Infection (documented clinically), skin (cellulitis)	0.43% 2/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.00% 0/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Infections and infestations Infection (documented clinically), upper airway NOS	0.43% 2/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.22% 1/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Infections and infestations Infection (documented clinically), urinary tract NOS	0.22% 1/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.00% 0/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Infections and infestations Infection (documented clinically), vein	0.00% 0/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.22% 1/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Infections and infestations Infection with normal ANC, blood	0.43% 2/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.44% 2/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Infections and infestations Infection with normal ANC, bronchus	0.22% 1/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.65% 3/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Infections and infestations Infection with normal ANC, catheter-related	0.22% 1/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.00% 0/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Infections and infestations Infection with normal ANC, colon	0.00% 0/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.22% 1/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Infections and infestations Febrile neutropenia	3.5% 16/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	1.7% 8/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Infections and infestations Infection with normal ANC, lung (pneumonia)	1.3% 6/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.65% 3/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Infections and infestations Infection with normal ANC, upper airway NOS	0.22% 1/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.00% 0/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Infections and infestations Infection - other	0.43% 2/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.22% 1/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Infections and infestations Infection with unknown ANC, anal/perianal	0.00% 0/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.22% 1/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Infections and infestations Infection with unknown ANC, lung (pneumonia)	1.1% 5/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.44% 2/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Infections and infestations Infection with unknown ANC, pleura (empyema)	0.00% 0/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.22% 1/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Blood and lymphatic system disorders Edema: limb	0.22% 1/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.00% 0/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Musculoskeletal and connective tissue disorders Fracture	0.43% 2/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	1.3% 6/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Musculoskeletal and connective tissue disorders Muscuskeletal - other	0.43% 2/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.22% 1/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Musculoskeletal and connective tissue disorders Muscle weakness, extremity-lower	0.00% 0/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.44% 2/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Musculoskeletal and connective tissue disorders Muscle weakness, whole body/generalized	0.22% 1/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.22% 1/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Metabolism and nutrition disorders Alkaline phosphatase	0.22% 1/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.00% 0/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Metabolism and nutrition disorders ALT	0.43% 2/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.00% 0/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Metabolism and nutrition disorders AST	0.22% 1/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.00% 0/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Metabolism and nutrition disorders Creatinine	0.22% 1/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.00% 0/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Metabolism and nutrition disorders GGT	0.22% 1/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.00% 0/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Metabolism and nutrition disorders Bilirubin (hyperbilirubinemia)	0.00% 0/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.22% 1/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Metabolism and nutrition disorders Hypercalcemia	0.00% 0/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.22% 1/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Metabolism and nutrition disorders Hyperglycemia	0.22% 1/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.00% 0/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Metabolism and nutrition disorders Hyperkalemia	0.00% 0/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.22% 1/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Metabolism and nutrition disorders Hypoglycemia	0.43% 2/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.00% 0/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Metabolism and nutrition disorders Hypokalemia	0.43% 2/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.00% 0/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Metabolism and nutrition disorders Hyponatremia	0.22% 1/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.22% 1/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Metabolism and nutrition disorders Hypophosphatemia	0.22% 1/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.00% 0/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Nervous system disorders Mood alteration, agitation	0.22% 1/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.00% 0/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Nervous system disorders CNS ischemia	0.22% 1/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	1.5% 7/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Nervous system disorders Confusion	1.3% 6/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.65% 3/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Nervous system disorders Dizziness	0.65% 3/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.44% 2/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Nervous system disorders Mood alteration, euphoria	0.00% 0/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.22% 1/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Nervous system disorders Speech impairment	0.22% 1/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.00% 0/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Nervous system disorders Mood alteration, depression	0.65% 3/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.00% 0/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Nervous system disorders Neuropathy: motor	0.22% 1/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.22% 1/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Nervous system disorders Neurology - other	0.43% 2/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	1.1% 5/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Nervous system disorders Neuropathy: sensory	0.65% 3/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	1.3% 6/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Nervous system disorders Seizure	0.65% 3/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.22% 1/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Nervous system disorders Syncope (fainting)	0.22% 1/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.22% 1/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
General disorders Pain, back	0.86% 4/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.44% 2/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
General disorders Pain, chest/thorax NOS	0.00% 0/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	1.1% 5/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
General disorders Pain, chest wall	0.22% 1/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.22% 1/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
General disorders Pain, tumor pain	0.43% 2/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.87% 4/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
General disorders Pain, abdomen NOS	0.65% 3/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.44% 2/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
General disorders Pain, joint	0.43% 2/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.00% 0/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
General disorders Pain, muscle	0.00% 0/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.22% 1/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
General disorders Pain, bone	0.65% 3/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.22% 1/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
General disorders Pain, liver	0.22% 1/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.00% 0/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
General disorders Pain, pain NOS	0.22% 1/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.00% 0/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
General disorders Pain, stomach	0.22% 1/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.00% 0/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Respiratory, thoracic and mediastinal disorders ARDS	0.22% 1/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.00% 0/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.86% 4/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	1.5% 7/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Respiratory, thoracic and mediastinal disorders Fistula, pulmonary, bronchus	0.00% 0/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.22% 1/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Respiratory, thoracic and mediastinal disorders Fistula, pulmonary, lung	0.22% 1/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.00% 0/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Respiratory, thoracic and mediastinal disorders Hypoxia	0.43% 2/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.00% 0/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Respiratory, thoracic and mediastinal disorders Airway obstruction, bronchus	0.00% 0/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.44% 2/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Respiratory, thoracic and mediastinal disorders Pulmonary - other	3.7% 17/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.87% 4/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Respiratory, thoracic and mediastinal disorders Pneumonitis	1.5% 7/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.22% 1/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Respiratory, thoracic and mediastinal disorders Pneumothorax	1.5% 7/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.00% 0/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Respiratory, thoracic and mediastinal disorders Dyspnea (shortness of breath)	5.2% 24/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	5.0% 23/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Respiratory, thoracic and mediastinal disorders Bronchospasm	0.22% 1/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.00% 0/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Renal and urinary disorders Cystitis	0.22% 1/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.22% 1/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Renal and urinary disorders Renal failure	0.86% 4/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.00% 0/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Renal and urinary disorders Urinary retention	0.00% 0/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.44% 2/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Skin and subcutaneous tissue disorders Hand-foot skin reaction	0.43% 2/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.00% 0/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Skin and subcutaneous tissue disorders Rash/desquamation	0.86% 4/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.00% 0/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Injury, poisoning and procedural complications Intraop injury, bone	0.22% 1/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.00% 0/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
General disorders Syndromes - other	0.22% 1/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.00% 0/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Vascular disorders Thrombosis/embolism (vascular access)	0.00% 0/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.65% 3/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Vascular disorders Vascular - other	0.00% 0/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.22% 1/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Vascular disorders Thrombosis/thrombus/embolism	3.5% 16/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	3.7% 17/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Blood and lymphatic system disorders Bone marrow cellularity	0.22% 1/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.44% 2/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Cardiac disorders Supraventricular arrhythmia, atrial	0.22% 1/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.00% 0/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Cardiac disorders cardiac general - other	0.22% 1/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.22% 1/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Gastrointestinal disorders ascites	0.22% 1/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.00% 0/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Gastrointestinal disorders Fistula, GI, abdomen NOS	0.00% 0/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.22% 1/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Gastrointestinal disorders perforation, GI, stomach	0.22% 1/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.00% 0/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Blood and lymphatic system disorders Hematoma	0.00% 0/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.22% 1/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Blood and lymphatic system disorders Hemorrhage, GI, esophagus	0.00% 0/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.22% 1/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Blood and lymphatic system disorders Hemorrhage, Gu, bladder	0.22% 1/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.00% 0/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Infections and infestations Infection (documented clinically), anal/perianal	0.22% 1/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.00% 0/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Infections and infestations Infection (documented clinically), mucosa	0.22% 1/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.00% 0/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Infections and infestations Infection with normal ANC, anal/perianal	0.43% 2/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.00% 0/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Infections and infestations Infection with normal ANC, pleura (empyema)	0.22% 1/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.00% 0/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Infections and infestations Infection with normal ANC, urethra	0.22% 1/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.00% 0/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Infections and infestations Opportunistic infection	0.22% 1/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.00% 0/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Infections and infestations Infection with unknown ANC, blood	0.00% 0/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.44% 2/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Infections and infestations Infection with unknown ANC, muscle (infection myositis)	0.22% 1/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.00% 0/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Nervous system disorders Cognitive disturbance	0.22% 1/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.00% 0/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
General disorders Pain, neck	0.22% 1/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.00% 0/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Skin and subcutaneous tissue disorders Bruising	0.00% 0/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.22% 1/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Skin and subcutaneous tissue disorders Flushing	0.22% 1/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.00% 0/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Surgical and medical procedures Intraop injury, lung	0.22% 1/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.00% 0/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
General disorders Flu-like syndrome	0.22% 1/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.00% 0/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Vascular disorders Peripheral arterial ischemia	0.00% 0/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.22% 1/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).

Other adverse events

Measure	Sorafenib + C/P n=463 participants at risk Chemotherapy Phase up to 6 cycles: Sorafenib (Nexavar, BAY43-9006), \[400 mg orally, twice daily\] on Study Days 2-19 and paclitaxel (P) (200 mg/m2, intravenous (IV)) and carboplatin (C) (area under the curve (AUC) =6 mg/ml\*min-1, IV) on Study Day 1. The cycle duration 21 days. Maintenance Phase: Sorafenib 400 mg orally twice daily was administered on Days 1-21 of each 21-day cycle.	Placebo + C/P n=459 participants at risk Chemotherapy Phase up to 6 cycles: Sorafenib Placebo (2 tablets orally twice daily\] on Study Days 2-19 and paclitaxel (200 mg/m2, intravenous (IV)) and carboplatin (area under the curve (AUC) =6 mg/ml\*min-1, IV) on Study Day 1. The cycle duration 21 days. Maintenance Phase: Sorafenib Placebo 2 tablets orally twice daily was administered on Days 1-21 of each 21-day cycle.
General disorders Pain, extremity-limb	14.9% 69/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	12.6% 58/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
General disorders Pain, abdomen NOS	13.0% 60/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	10.9% 50/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
General disorders Pain, head/headache	11.2% 52/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	10.9% 50/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
General disorders Pain, joint	17.9% 83/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	21.8% 100/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
General disorders Pain, muscle	20.7% 96/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	26.1% 120/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
General disorders Pain, bone	11.2% 52/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	8.9% 41/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
General disorders Pain, chest/thorax NOS	15.1% 70/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	15.3% 70/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Blood and lymphatic system disorders Neutrophils	36.7% 170/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	36.6% 168/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Blood and lymphatic system disorders Hemoglobin	31.3% 145/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	32.2% 148/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Blood and lymphatic system disorders Platelets	30.2% 140/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	14.6% 67/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Blood and lymphatic system disorders Leukocytes	16.8% 78/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	14.6% 67/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Cardiac disorders Hypertension	19.4% 90/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	10.0% 46/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
General disorders Fever	18.4% 85/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	13.1% 60/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
General disorders Insomnia	17.1% 79/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	18.1% 83/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
General disorders Fatigue	54.2% 251/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	49.7% 228/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
General disorders Weight loss	21.4% 99/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	12.4% 57/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Gastrointestinal disorders Anorexia	32.2% 149/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	26.6% 122/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Gastrointestinal disorders Constipation	27.2% 126/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	23.3% 107/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Gastrointestinal disorders Diarrhea	44.3% 205/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	23.3% 107/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Gastrointestinal disorders Heartburn	10.2% 47/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	5.7% 26/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Gastrointestinal disorders Mucositis (clinical exam), oral cavity	16.6% 77/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	7.2% 33/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Gastrointestinal disorders Nausea	43.4% 201/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	44.4% 204/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Gastrointestinal disorders Vomiting	26.3% 122/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	23.5% 108/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Blood and lymphatic system disorders Edema: limb	11.2% 52/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	11.1% 51/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Nervous system disorders Dizziness	11.9% 55/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	11.3% 52/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Nervous system disorders Neuropathy: sensory	51.0% 236/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	54.5% 250/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
General disorders Pain, back	10.8% 50/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	11.5% 53/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Respiratory, thoracic and mediastinal disorders Cough	30.7% 142/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	30.1% 138/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Respiratory, thoracic and mediastinal disorders Dyspnea (shortness of breath)	29.8% 138/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	29.6% 136/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Skin and subcutaneous tissue disorders Alopecia	46.2% 214/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	46.8% 215/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Skin and subcutaneous tissue disorders Hand-foot skin reaction	24.4% 113/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	5.2% 24/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Skin and subcutaneous tissue disorders Pruritus	14.3% 66/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	7.6% 35/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Skin and subcutaneous tissue disorders Rash/desquamation	51.6% 239/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	17.4% 80/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Immune system disorders Allergic reaction	6.3% 29/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	6.5% 30/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Cardiac disorders Hypotension	7.8% 36/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	6.1% 28/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
General disorders Sweating	6.5% 30/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	6.8% 31/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Gastrointestinal disorders Dehydration	7.8% 36/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	3.5% 16/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Gastrointestinal disorders Mucositis (functional/symptomatic), oral cavity	5.4% 25/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	2.6% 12/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Gastrointestinal disorders Taste alteration	9.3% 43/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	8.3% 38/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Vascular disorders Hemorrhage pulmonary, nose	9.9% 46/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	4.6% 21/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
General disorders Pain, throat / pharynx / larynx	5.2% 24/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	3.7% 17/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Metabolism and nutrition disorders Hypokalemia	9.9% 46/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	5.4% 25/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Metabolism and nutrition disorders Hypomagnesemia	8.6% 40/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	5.7% 26/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Nervous system disorders Mood alteration, anxiety	9.1% 42/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	7.6% 35/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Nervous system disorders Mood alteration, depression	6.0% 28/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	4.4% 20/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Respiratory, thoracic and mediastinal disorders Voice changes	6.0% 28/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	4.8% 22/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Skin and subcutaneous tissue disorders Dry skin	8.9% 41/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	5.2% 24/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Skin and subcutaneous tissue disorders Erythema multiforme	5.4% 25/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	0.87% 4/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
General disorders Pain, tumor pain	4.8% 22/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	5.0% 23/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Immune system disorders Rhinitis	3.9% 18/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	5.0% 23/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Musculoskeletal and connective tissue disorders Muscle weakness, whole body / generalized	5.8% 27/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	4.4% 20/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).
Metabolism and nutrition disorders Hyperglycemia	4.1% 19/463 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).	5.0% 23/459 • The adverse event data were collected from the first subject's first visit (13 Feb 2006) to the planned formal interim analysis (01 Oct 2007 data cut-off date), and additional safety data were collected until the last subject's last visit (05 Feb 2009).

Additional Information

Therapeutic Area Head

BAYER

Email: clinical-trials-contact@bayerhealthcare.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: LTE60