Trial Outcomes & Findings for Pilot Study of Docetaxel & Bevacizumab +/- Trastuzumab in First-Line Treatment of Patients With Metastatic Breast Cancer (NCT NCT00364611)

NCT ID: NCT00364611

Last Updated: 2012-08-23

Results Overview

PFS was the time from registration to first documentation of * progressive disease (PD) based on Response Evaluation Criteria in Solid Tumors (RECIST) - criteria pre-defining changes in lesion size or appearance * symptomatic deterioration * death due to any cause (in absence of PD). The Percentage of participants with PFS is reported. For the analysis, participants were censored * on the last available tumor assessment date on study treatment if they * had no PFS event * were on anticancer therapy not related to study treatment * on the registration date if they * did not receive study drug * had no post baseline tumor assessment

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 73 participants
• Primary outcome timeframe: Up to 6 months and 12 months after treatment initiation
• Results posted on: 2012-08-23

Participant Flow

103 participants signed the informed consent for this study. Of these, 73 were determined to be eligible for inclusion. One participant did not receive any study treatment.

Participant milestones

Measure	Docetaxel and Bevacizumab Stratum 1: HER2 Negative participants with metastatic breast cancer treated with DB (docetaxel and bevacizumab) intravenously (IV) every 3 weeks (q3w) until treatment discontinuation criteria (unacceptable toxicity, disease progression or death) are met	Docetaxel, Bevacizumab and Trastuzumab Stratum 2: HER2 Positive participants with metastatic breast cancer treated with DBT (docetaxel, bevacizumab, and trastuzumab) IV q3w until treatment discontinuation criteria (unacceptable toxicity, disease progression or death) are met
Overall Study STARTED	52	21
Overall Study TREATED (SAFTEY POPULATION)	52	20
Overall Study COMPLETED	1	0
Overall Study NOT COMPLETED	51	21

Reasons for withdrawal

Measure	Docetaxel and Bevacizumab Stratum 1: HER2 Negative participants with metastatic breast cancer treated with DB (docetaxel and bevacizumab) intravenously (IV) every 3 weeks (q3w) until treatment discontinuation criteria (unacceptable toxicity, disease progression or death) are met	Docetaxel, Bevacizumab and Trastuzumab Stratum 2: HER2 Positive participants with metastatic breast cancer treated with DBT (docetaxel, bevacizumab, and trastuzumab) IV q3w until treatment discontinuation criteria (unacceptable toxicity, disease progression or death) are met
Overall Study Did not receive study medication	0	1
Overall Study Adverse Event	7	4
Overall Study Participant's Request	3	4
Overall Study Disease Progression	38	8
Overall Study Investigator decision	2	2
Overall Study Found Ineligible	1	0
Overall Study Presumed CR on Study	0	1
Overall Study Receiving Liver Ablation	0	1

Baseline Characteristics

Pilot Study of Docetaxel & Bevacizumab +/- Trastuzumab in First-Line Treatment of Patients With Metastatic Breast Cancer

Baseline characteristics by cohort

Measure	Docetaxel and Bevacizumab n=52 Participants Stratum 1: HER2 Negative participants with metastatic breast cancer treated with DB (docetaxel and bevacizumab) intravenously (IV) every 3 weeks (q3w) until treatment discontinuation criteria (unacceptable toxicity, disease progression or death) are met	Docetaxel, Bevacizumab and Trastuzumab n=21 Participants Stratum 2: HER2 Positive participants with metastatic breast cancer treated with DBT (docetaxel, bevacizumab, and trastuzumab) IV q3w until treatment discontinuation criteria (unacceptable toxicity, disease progression or death) are met	Total n=73 Participants Total of all reporting groups
Age Continuous	56.2 years STANDARD_DEVIATION 10.78 • n=5 Participants	52.8 years STANDARD_DEVIATION 12.65 • n=7 Participants	55.2 years STANDARD_DEVIATION 11.37 • n=5 Participants
Age, Customized <=65 years	41 participants n=5 Participants	17 participants n=7 Participants	58 participants n=5 Participants
Age, Customized Between 65 and 75 years	8 participants n=5 Participants	3 participants n=7 Participants	11 participants n=5 Participants
Age, Customized >=75 years	3 participants n=5 Participants	1 participants n=7 Participants	4 participants n=5 Participants
Sex: Female, Male Female	52 Participants n=5 Participants	21 Participants n=7 Participants	73 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Eastern Cooperative Oncology ECOG Performance Score is 0	28 participants n=5 Participants	16 participants n=7 Participants	44 participants n=5 Participants
Eastern Cooperative Oncology ECOG Performance Score is 1	24 participants n=5 Participants	5 participants n=7 Participants	29 participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 6 months and 12 months after treatment initiation

Population: Intent to treat population: all registered participants

PFS was the time from registration to first documentation of

• progressive disease (PD) based on Response Evaluation Criteria in Solid Tumors (RECIST) - criteria pre-defining changes in lesion size or appearance
• symptomatic deterioration
• death due to any cause (in absence of PD).

The Percentage of participants with PFS is reported.

For the analysis, participants were censored

• on the last available tumor assessment date on study treatment if they

• had no PFS event
• were on anticancer therapy not related to study treatment
• on the registration date if they

• did not receive study drug
• had no post baseline tumor assessment

Outcome measures

Measure	Docetaxel and Bevacizumab n=52 Participants Stratum 1: HER2 Negative participants with metastatic breast cancer treated with DB (docetaxel and bevacizumab) intravenously (IV) every 3 weeks (q3w) until treatment discontinuation criteria (unacceptable toxicity, disease progression or death) are met	Docetaxel, Bevacizumab and Trastuzumab n=21 Participants Stratum 2: HER2 Positive participants with metastatic breast cancer treated with DBT (docetaxel, bevacizumab, and trastuzumab) IV q3w until treatment discontinuation criteria (unacceptable toxicity, disease progression or death) are met
Progression-free Survival (PFS) Rate: Percentage of Participants With PFS PFS rate at 6 months	59.6 percentage of participants Interval 45.1 to 73.0	90.5 percentage of participants Interval 69.6 to 98.8
Progression-free Survival (PFS) Rate: Percentage of Participants With PFS PFS rate at 12 months	30.8 percentage of participants Interval 18.7 to 45.1	81.0 percentage of participants Interval 58.1 to 94.6

PRIMARY outcome

Timeframe: From treatment initiation to PFS event (up to June 2011)

Population: Intent-to-treat population: all registered participants

Time to PFS was the interval from the date of registration to the earliest of the following documented dates:

• PD as defined by RECIST (criteria pre-defining changes in lesion size or appearance)
• symptomatic deterioration
• death.

Time to PFS was estimated from Kaplan-Meier Plots.

Outcome measures

Measure	Docetaxel and Bevacizumab n=45 PFS events analyzed Stratum 1: HER2 Negative participants with metastatic breast cancer treated with DB (docetaxel and bevacizumab) intravenously (IV) every 3 weeks (q3w) until treatment discontinuation criteria (unacceptable toxicity, disease progression or death) are met	Docetaxel, Bevacizumab and Trastuzumab n=10 PFS events analyzed Stratum 2: HER2 Positive participants with metastatic breast cancer treated with DBT (docetaxel, bevacizumab, and trastuzumab) IV q3w until treatment discontinuation criteria (unacceptable toxicity, disease progression or death) are met
Time to Progression-free Survival (PFS)	255 days Interval 158.0 to 315.0	403 days Interval 363.0 to 1078.0

SECONDARY outcome

Timeframe: From treatment initiation to June 2011

Population: Intent-to-treat population: all registered participants.

Confirmed OR was confirmed Complete Response (CR) + confirmed Partial Response (PR). According to RECIST

• CR was the disappearance of all tumor lesions
• PR was a pre-defined decrease in the size of tumor lesions.

To determine a response, radiologic tumors assessments were performed using computed tomography (CT) and/or magnetic resonance imaging (MRI) of the chest, and the abdomen, bone scan or positron emission tomography (PET) scan, and other imaging techniques as clinically indicated. To confirm a response, 2 assessments separated by 28 days or more were required.

Outcome measures

Measure	Docetaxel and Bevacizumab n=52 Participants Stratum 1: HER2 Negative participants with metastatic breast cancer treated with DB (docetaxel and bevacizumab) intravenously (IV) every 3 weeks (q3w) until treatment discontinuation criteria (unacceptable toxicity, disease progression or death) are met	Docetaxel, Bevacizumab and Trastuzumab n=21 Participants Stratum 2: HER2 Positive participants with metastatic breast cancer treated with DBT (docetaxel, bevacizumab, and trastuzumab) IV q3w until treatment discontinuation criteria (unacceptable toxicity, disease progression or death) are met
Confirmed Overall Response (OR) Based on RECIST Criteria Confirmed overall response	30 participants	17 participants
Confirmed Overall Response (OR) Based on RECIST Criteria Confirmed complete response	3 participants	4 participants
Confirmed Overall Response (OR) Based on RECIST Criteria Confirmed partial response	27 participants	13 participants

SECONDARY outcome

Timeframe: From treatment initiation to June 2011

Population: Intent-to-treat: all registered participants.

Clinical Benefit (CB) was achieved in participants with a response (CR + PR) or a stable disease (SD).

According to RECIST

• CR was the disappearance of all tumor lesions
• PR was a pre-defined decrease in the size of tumor lesions
• SD was neither sufficient decrease in tumor size to qualify for PR or sufficient increase to qualify for PD.

Confirmation of a response needed 2 responses scored, separated by 28 days or more (for CR and PR), and by 26 weeks or more (for SD).

Outcome measures

Measure	Docetaxel and Bevacizumab n=52 Participants Stratum 1: HER2 Negative participants with metastatic breast cancer treated with DB (docetaxel and bevacizumab) intravenously (IV) every 3 weeks (q3w) until treatment discontinuation criteria (unacceptable toxicity, disease progression or death) are met	Docetaxel, Bevacizumab and Trastuzumab n=21 Participants Stratum 2: HER2 Positive participants with metastatic breast cancer treated with DBT (docetaxel, bevacizumab, and trastuzumab) IV q3w until treatment discontinuation criteria (unacceptable toxicity, disease progression or death) are met
Number of Participants With Confirmed Clinical Benefit Based on RECIST Criteria with confirmed Clinical Benefit (CR+PR+SD)	35 participants	17 participants
Number of Participants With Confirmed Clinical Benefit Based on RECIST Criteria with confirmed CR	3 participants	4 participants
Number of Participants With Confirmed Clinical Benefit Based on RECIST Criteria with confirmed PR	27 participants	13 participants
Number of Participants With Confirmed Clinical Benefit Based on RECIST Criteria with confirmed SD	14 participants	1 participants

SECONDARY outcome

Timeframe: From treatment initiation to June 2011

Population: Participants with a documented response of CR or PR.

DR was the interval from date of initial documented confirmed response (CR or PR) to the first documented confirmed date of disease progression (PD) or death from any cause in the absence of previous documentation of objective tumor progression.

Participants who were alive and without any record of PD at the time of discontinuation were censored at the last available tumor assessment date; participants with non-study anti-cancer therapy during the study were censored at the last available tumor assessment date prior to the anti-cancer therapy.

DR was estimated from Kaplan-Meier Plots.

Outcome measures

Measure	Docetaxel and Bevacizumab n=25 Events (PD or death after 1st Response) Stratum 1: HER2 Negative participants with metastatic breast cancer treated with DB (docetaxel and bevacizumab) intravenously (IV) every 3 weeks (q3w) until treatment discontinuation criteria (unacceptable toxicity, disease progression or death) are met	Docetaxel, Bevacizumab and Trastuzumab n=8 Events (PD or death after 1st Response) Stratum 2: HER2 Positive participants with metastatic breast cancer treated with DBT (docetaxel, bevacizumab, and trastuzumab) IV q3w until treatment discontinuation criteria (unacceptable toxicity, disease progression or death) are met
Duration of Response (DR)	232 days Interval 126.0 to 305.0	366 days Interval 293.0 to 859.0

SECONDARY outcome

Timeframe: From treatment initiation to June 2011

Population: Intent-to-treat population: all registered participants.

OS was the interval between the date of study entry and the date of death from any cause. In the absence of confirmation of death, survival time was censored at the last date the participant was known to be alive.

OS time was estimated from Kaplan-Meier Plots.

Outcome measures

Measure	Docetaxel and Bevacizumab n=33 Deaths Stratum 1: HER2 Negative participants with metastatic breast cancer treated with DB (docetaxel and bevacizumab) intravenously (IV) every 3 weeks (q3w) until treatment discontinuation criteria (unacceptable toxicity, disease progression or death) are met	Docetaxel, Bevacizumab and Trastuzumab n=6 Deaths Stratum 2: HER2 Positive participants with metastatic breast cancer treated with DBT (docetaxel, bevacizumab, and trastuzumab) IV q3w until treatment discontinuation criteria (unacceptable toxicity, disease progression or death) are met
Overall Survival (OS) Time	750 days Interval 362.0 to 1159.0	986 days Interval 619.0 to 1705.0

SECONDARY outcome

Timeframe: From treatment initiation to 30 days after the last dose of study treatment

Population: Safety population: all participants who received at least one dose of study medication

An adverse event (AE) was any unfavorable and unintended sign, symptom, syndrome, or illness that developed or worsened during the clinical study. AEs occurring on or after first dose of study medication inclusive to 30 days post-last dose were the treatment emergent adverse events (TEAEs).

An serious adverse event was an AE that at any dose (including overdose) resulted in death, was life-threatening, required or prolonged inpatient hospitalization, resulted in persistent or significant disability or incapacity, was a congenital anomaly, and/or was medically important.

Outcome measures

Measure	Docetaxel and Bevacizumab n=52 Participants Stratum 1: HER2 Negative participants with metastatic breast cancer treated with DB (docetaxel and bevacizumab) intravenously (IV) every 3 weeks (q3w) until treatment discontinuation criteria (unacceptable toxicity, disease progression or death) are met	Docetaxel, Bevacizumab and Trastuzumab n=20 Participants Stratum 2: HER2 Positive participants with metastatic breast cancer treated with DBT (docetaxel, bevacizumab, and trastuzumab) IV q3w until treatment discontinuation criteria (unacceptable toxicity, disease progression or death) are met
Number of Participants With Adverse Events (AE) with treatment emergent adverse events (TEAEs)	52 participants	20 participants
Number of Participants With Adverse Events (AE) with serious adverse events	14 participants	4 participants
Number of Participants With Adverse Events (AE) with TEAEs resulting in death	3 participants	0 participants

Adverse Events

Docetaxel and Bevacizumab

Serious events: 14 serious events

Other events: 52 other events

Deaths: 0 deaths

Docetaxel, Bevacizumab and Trastuzumab

Serious events: 4 serious events

Other events: 20 other events

Deaths: 0 deaths

Serious adverse events

Measure	Docetaxel and Bevacizumab n=52 participants at risk Stratum 1: HER2 Negative participants with metastatic breast cancer treated with DB (docetaxel and bevacizumab) intravenously (IV) every 3 weeks (q3w) until treatment discontinuation criteria (unacceptable toxicity, disease progression or death) are met	Docetaxel, Bevacizumab and Trastuzumab n=20 participants at risk Stratum 2: HER2 Positive participants with metastatic breast cancer treated with DBT (docetaxel, bevacizumab, and trastuzumab) IV q3w until treatment discontinuation criteria (unacceptable toxicity, disease progression or death) are met
Blood and lymphatic system disorders Febrile neutropenia	1.9% 1/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	0.00% 0/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Cardiac disorders Tachycardia	1.9% 1/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	0.00% 0/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Cardiac disorders Atrial fibrillation	0.00% 0/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	5.0% 1/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Gastrointestinal disorders Duodenal ulcer	1.9% 1/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	0.00% 0/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Gastrointestinal disorders Gastric ulcer	1.9% 1/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	0.00% 0/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Gastrointestinal disorders Nausea	1.9% 1/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	0.00% 0/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Gastrointestinal disorders Abdominal pain	0.00% 0/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	5.0% 1/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
General disorders Asthenia	1.9% 1/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	0.00% 0/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
General disorders Disease progression	1.9% 1/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	0.00% 0/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
General disorders Mucosal inflammation	1.9% 1/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	0.00% 0/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Infections and infestations Appendicitis	1.9% 1/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	0.00% 0/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Infections and infestations Breast infection	1.9% 1/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	0.00% 0/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Infections and infestations Peridiverticular abscess	1.9% 1/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	0.00% 0/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Infections and infestations Rectal abscess	1.9% 1/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	0.00% 0/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Infections and infestations Catheter site infection	0.00% 0/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	5.0% 1/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Infections and infestations Perirectal abscess	0.00% 0/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	5.0% 1/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Infections and infestations Pneumonia	0.00% 0/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	5.0% 1/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Metabolism and nutrition disorders Decreased appetite	1.9% 1/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	0.00% 0/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Metabolism and nutrition disorders Dehydration	1.9% 1/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	5.0% 1/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Musculoskeletal and connective tissue disorders Arthralgia	1.9% 1/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	0.00% 0/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Musculoskeletal and connective tissue disorders Back pain	1.9% 1/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	0.00% 0/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Musculoskeletal and connective tissue disorders Bone pain	1.9% 1/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	0.00% 0/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Musculoskeletal and connective tissue disorders Neck pain	1.9% 1/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	0.00% 0/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Musculoskeletal and connective tissue disorders Pain in extremity	1.9% 1/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	0.00% 0/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer metastatic	1.9% 1/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	0.00% 0/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to meninges	1.9% 1/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	0.00% 0/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasm malignant	1.9% 1/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	0.00% 0/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Nervous system disorders Ataxia	1.9% 1/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	0.00% 0/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Nervous system disorders Vocal cord paralysis	1.9% 1/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	0.00% 0/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Psychiatric disorders Confusional state	1.9% 1/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	0.00% 0/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Renal and urinary disorders Renal failure acute	1.9% 1/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	0.00% 0/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Respiratory, thoracic and mediastinal disorders Pleural effusion	5.8% 3/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	5.0% 1/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	1.9% 1/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	0.00% 0/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Respiratory, thoracic and mediastinal disorders Dyspnoea	1.9% 1/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	0.00% 0/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Respiratory, thoracic and mediastinal disorders Hypoxia	1.9% 1/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	0.00% 0/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	1.9% 1/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	0.00% 0/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Respiratory, thoracic and mediastinal disorders Respiratory distress	1.9% 1/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	0.00% 0/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Respiratory, thoracic and mediastinal disorders Respiratory failure	1.9% 1/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	0.00% 0/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Respiratory, thoracic and mediastinal disorders Upper airway obstruction	1.9% 1/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	0.00% 0/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Vascular disorders Deep vein thrombosis	1.9% 1/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	0.00% 0/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Vascular disorders Hypertension	1.9% 1/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	0.00% 0/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Vascular disorders Hypotension	1.9% 1/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	0.00% 0/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.

Other adverse events

Measure	Docetaxel and Bevacizumab n=52 participants at risk Stratum 1: HER2 Negative participants with metastatic breast cancer treated with DB (docetaxel and bevacizumab) intravenously (IV) every 3 weeks (q3w) until treatment discontinuation criteria (unacceptable toxicity, disease progression or death) are met	Docetaxel, Bevacizumab and Trastuzumab n=20 participants at risk Stratum 2: HER2 Positive participants with metastatic breast cancer treated with DBT (docetaxel, bevacizumab, and trastuzumab) IV q3w until treatment discontinuation criteria (unacceptable toxicity, disease progression or death) are met
Blood and lymphatic system disorders Anaemia	13.5% 7/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	15.0% 3/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Blood and lymphatic system disorders Neutropenia	7.7% 4/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	5.0% 1/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Blood and lymphatic system disorders Thrombocytopenia	3.8% 2/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	10.0% 2/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Cardiac disorders Tachycardia	5.8% 3/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	5.0% 1/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Eye disorders Lacrimation increased	28.8% 15/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	50.0% 10/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Eye disorders Dry eye	5.8% 3/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	5.0% 1/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Gastrointestinal disorders Nausea	53.8% 28/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	50.0% 10/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Gastrointestinal disorders Diarrhoea	44.2% 23/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	40.0% 8/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Gastrointestinal disorders Constipation	32.7% 17/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	20.0% 4/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Gastrointestinal disorders Vomiting	23.1% 12/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	35.0% 7/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Gastrointestinal disorders Stomatitis	17.3% 9/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	30.0% 6/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Gastrointestinal disorders Dyspepsia	11.5% 6/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	15.0% 3/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Gastrointestinal disorders Abdominal pain	7.7% 4/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	5.0% 1/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Gastrointestinal disorders Gastrooesophageal reflux disease	5.8% 3/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	5.0% 1/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Gastrointestinal disorders Haemorrhoids	5.8% 3/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	5.0% 1/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Gastrointestinal disorders Dry mouth	3.8% 2/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	10.0% 2/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
General disorders Fatigue	69.2% 36/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	65.0% 13/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
General disorders Mucosal inflammation	26.9% 14/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	15.0% 3/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
General disorders Oedema peripheral	23.1% 12/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	15.0% 3/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
General disorders Pain	9.6% 5/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	10.0% 2/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
General disorders Pyrexia	9.6% 5/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	10.0% 2/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
General disorders Chills	7.7% 4/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	5.0% 1/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
General disorders Chest pain	5.8% 3/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	0.00% 0/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
General disorders Asthenia	1.9% 1/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	15.0% 3/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Infections and infestations Urinary tract infection	17.3% 9/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	30.0% 6/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Infections and infestations Sinusitis	15.4% 8/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	25.0% 5/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Infections and infestations Furuncle	7.7% 4/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	5.0% 1/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Infections and infestations Upper respiratory tract infection	7.7% 4/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	15.0% 3/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Infections and infestations Nail infection	5.8% 3/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	20.0% 4/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Infections and infestations Nasopharyngitis	1.9% 1/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	10.0% 2/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Infections and infestations Eye infection	0.00% 0/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	10.0% 2/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Investigations Weight decreased	15.4% 8/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	5.0% 1/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Investigations Alanine aminotransferase increased	7.7% 4/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	0.00% 0/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Investigations Aspartate aminotransferase increased	7.7% 4/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	0.00% 0/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Investigations Blood creatinine increased	5.8% 3/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	0.00% 0/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Investigations Ejection fraction decreased	1.9% 1/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	10.0% 2/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Metabolism and nutrition disorders Decreased appetite	19.2% 10/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	25.0% 5/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Metabolism and nutrition disorders Hyperglycaemia	9.6% 5/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	15.0% 3/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Metabolism and nutrition disorders Dehydration	7.7% 4/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	0.00% 0/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Musculoskeletal and connective tissue disorders Arthralgia	32.7% 17/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	30.0% 6/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Musculoskeletal and connective tissue disorders Pain in extremity	23.1% 12/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	20.0% 4/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Musculoskeletal and connective tissue disorders Back pain	21.2% 11/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	10.0% 2/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Musculoskeletal and connective tissue disorders Bone pain	17.3% 9/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	25.0% 5/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	11.5% 6/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	0.00% 0/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Musculoskeletal and connective tissue disorders Muscle spasms	7.7% 4/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	0.00% 0/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	5.8% 3/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	0.00% 0/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Musculoskeletal and connective tissue disorders Myalgia	5.8% 3/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	15.0% 3/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Musculoskeletal and connective tissue disorders Muscular weakness	3.8% 2/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	10.0% 2/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Nervous system disorders Dysgeusia	38.5% 20/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	40.0% 8/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Nervous system disorders Headache	30.8% 16/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	45.0% 9/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Nervous system disorders Neuropathy peripheral	21.2% 11/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	20.0% 4/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Nervous system disorders Peripheral sensory neuropathy	13.5% 7/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	20.0% 4/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Nervous system disorders Dizziness	11.5% 6/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	5.0% 1/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Nervous system disorders Memory impairment	5.8% 3/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	5.0% 1/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Nervous system disorders Hypoaesthesia	0.00% 0/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	10.0% 2/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Nervous system disorders Paraesthesia	0.00% 0/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	10.0% 2/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Psychiatric disorders Insomnia	19.2% 10/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	25.0% 5/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Psychiatric disorders Anxiety	13.5% 7/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	20.0% 4/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Psychiatric disorders Depression	1.9% 1/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	10.0% 2/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Renal and urinary disorders Proteinuria	13.5% 7/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	15.0% 3/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Renal and urinary disorders Dysuria	7.7% 4/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	0.00% 0/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Reproductive system and breast disorders Breast pain	7.7% 4/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	15.0% 3/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Reproductive system and breast disorders Vaginal haemorrhage	5.8% 3/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	10.0% 2/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Respiratory, thoracic and mediastinal disorders Epistaxis	32.7% 17/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	40.0% 8/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Respiratory, thoracic and mediastinal disorders Dyspnoea	13.5% 7/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	5.0% 1/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Respiratory, thoracic and mediastinal disorders Cough	9.6% 5/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	25.0% 5/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Respiratory, thoracic and mediastinal disorders Pleural effusion	9.6% 5/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	5.0% 1/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Respiratory, thoracic and mediastinal disorders Dysphonia	7.7% 4/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	0.00% 0/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	7.7% 4/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	15.0% 3/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Respiratory, thoracic and mediastinal disorders Sinus congestion	7.7% 4/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	10.0% 2/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	5.8% 3/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	25.0% 5/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Respiratory, thoracic and mediastinal disorders Sinus disorder	0.00% 0/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	10.0% 2/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Skin and subcutaneous tissue disorders Alopecia	65.4% 34/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	75.0% 15/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Skin and subcutaneous tissue disorders Nail disorder	34.6% 18/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	35.0% 7/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Skin and subcutaneous tissue disorders Erythema	9.6% 5/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	5.0% 1/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Skin and subcutaneous tissue disorders Dry skin	7.7% 4/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	5.0% 1/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysaesthesia syndrome	5.8% 3/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	15.0% 3/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Skin and subcutaneous tissue disorders Pruritus	5.8% 3/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	10.0% 2/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Skin and subcutaneous tissue disorders Skin ulcer	5.8% 3/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	5.0% 1/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Skin and subcutaneous tissue disorders Skin exfoliation	3.8% 2/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	10.0% 2/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Skin and subcutaneous tissue disorders Rash	1.9% 1/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	30.0% 6/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Skin and subcutaneous tissue disorders Dermatitis acneiform	0.00% 0/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	10.0% 2/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Skin and subcutaneous tissue disorders Ingrowing nail	0.00% 0/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	10.0% 2/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Surgical and medical procedures Sinus operation	1.9% 1/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	10.0% 2/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Vascular disorders Hypertension	13.5% 7/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	40.0% 8/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.
Vascular disorders Hot flush	1.9% 1/52 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.	20.0% 4/20 • From treatment initiation up to 30 days following the last dose of study medication (upto April 2012) All participants (except one) were off study treatment on 30 June 2011. An initial safety analysis was performed using the cut-off date of June 2011. One participant continued till 19 April 2012. For this participant, adverse events were collected upto April 2012 and included in the final safety analysis.

Additional Information

Trial Transparency Team

Sanofi-aventis

Email: Contact-us@sanofi.com

Results disclosure agreements

• Principal investigator is a sponsor employee The investigator shall have the right to independently publish study results from his site after a multicenter publication, or 12 months after the completion of the study by all sites. He must provide the sponsor a copy of any such publication derived from the study for review and comment at least 60 days in advance of any submission for publication. The Sponsor may request for the publication to be delayed for a limited time, not to exceed 90 days to preserve its proprietary rights.
• Publication restrictions are in place

Restriction type: OTHER