Trial Outcomes & Findings for A Study in Subjects With Recurrent Malignant Glioma (NCT NCT01137604)

NCT ID: NCT01137604

Last Updated: 2022-09-29

Results Overview

PFS at Month 6 was defined as the percentage of participants who remained alive and progression-free at Month 6, based on investigator's assessment. Progression was defined using Response Assessment in Neuro-Oncology (RANO) criteria, as a greater than 25% increase in enhancing lesions despite stable or increasing steroid dose, an increase (significant) in non-enhancing T2-weighted-Fluid-Attenuated Inversion Recovery (T2/FLAIR) lesions that are not attributable to other non-tumor causes, and any new lesions. PFS rate at Month 6 was estimated from Kaplan-Meier (K-M) product-limit estimate of PFS.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 151 participants
• Primary outcome timeframe: At Month 6 from randomization (Cohort 1) or first day of treatment (Cohorts 2 and 3)
• Results posted on: 2022-09-29

Participant Flow

A total of 173 participants were screened and of those, 152 participants were deemed eligible, and 151 received study treatment.

The protocol definition of study completion was that the participant had disease progression. Protocol defined reasons for not completing were adverse event, participant choice, lost to follow-up, administrative/other (including withdrawal of consent, pregnancy, study terminated by sponsor or other). Death was not a protocol defined reason for non-completion. Participants were followed for survival until death, except where they withdrew consent, or the Sponsor stopped the survival follow-up.

Participant milestones

Measure	Cohort 1 - Bevacizumab Participants with recurrent Grade 4 malignant glioma (ie, glioblastoma \[GBM\]) who were bevacizumab-naive; received bevacizumab 10 mg/kg administered intravenously every 2 weeks in 28-day cycles	Cohort 1 - Lenvatinib Participants with recurrent Grade 4 malignant glioma (ie, glioblastoma \[GBM\]) who were bevacizumab-naive; received lenvatinib capsules 24 mg taken orally, once daily continuously in 28-day cycles	Cohort 2 - Lenvatinib Participants with recurrent Grade 3 malignant glioma who were bevacizumab-naive; received lenvatinib capsules 24 mg taken orally, once daily continuously in 28-day cycles	Cohort 3 - Lenvatinib Participants with recurrent GBM who had disease progression following prior bevacizumab treatment; received lenvatinib capsules 24 mg taken orally, once daily continuously in 28-day cycles
Overall Study STARTED	38	42	39	32
Overall Study Treatment Discontinued Due to Disease Progression	34	32	26	21
Overall Study COMPLETED	34	32	26	21
Overall Study NOT COMPLETED	4	10	13	11

Reasons for withdrawal

Measure	Cohort 1 - Bevacizumab Participants with recurrent Grade 4 malignant glioma (ie, glioblastoma \[GBM\]) who were bevacizumab-naive; received bevacizumab 10 mg/kg administered intravenously every 2 weeks in 28-day cycles	Cohort 1 - Lenvatinib Participants with recurrent Grade 4 malignant glioma (ie, glioblastoma \[GBM\]) who were bevacizumab-naive; received lenvatinib capsules 24 mg taken orally, once daily continuously in 28-day cycles	Cohort 2 - Lenvatinib Participants with recurrent Grade 3 malignant glioma who were bevacizumab-naive; received lenvatinib capsules 24 mg taken orally, once daily continuously in 28-day cycles	Cohort 3 - Lenvatinib Participants with recurrent GBM who had disease progression following prior bevacizumab treatment; received lenvatinib capsules 24 mg taken orally, once daily continuously in 28-day cycles
Overall Study Adverse Event	3	6	9	9
Overall Study Participant Choice	0	2	2	0
Overall Study Withdrawal of consent	0	0	0	2
Overall Study Clinical progression/deterioration	1	2	2	0

Baseline Characteristics

A Study in Subjects With Recurrent Malignant Glioma

Baseline characteristics by cohort

Measure	Cohort 1 - Bevacizumab n=38 Participants Participants with recurrent Grade 4 malignant glioma (ie, glioblastoma \[GBM\]) who were bevacizumab-naive; received bevacizumab 10 mg/kg administered intravenously every 2 weeks in 28-day cycles	Cohort 1 - Lenvatinib n=42 Participants Participants with recurrent Grade 4 malignant glioma (ie, glioblastoma \[GBM\]) who were bevacizumab-naive; received lenvatinib capsules 24 mg taken orally, once daily continuously in 28-day cycles	Cohort 2 - Lenvatinib n=39 Participants Participants with recurrent Grade 3 malignant glioma who were bevacizumab-naive; received lenvatinib capsules 24 mg taken orally, once daily continuously in 28-day cycles	Cohort 3 - Lenvatinib n=32 Participants Participants with recurrent GBM who had disease progression following prior bevacizumab treatment; received lenvatinib capsules 24 mg taken orally, once daily continuously in 28-day cycles	Total n=151 Participants Total of all reporting groups
Age, Continuous	55.1 Years STANDARD_DEVIATION 10.61 • n=5 Participants	55.5 Years STANDARD_DEVIATION 11.96 • n=7 Participants	49.2 Years STANDARD_DEVIATION 11.35 • n=5 Participants	53.0 Years STANDARD_DEVIATION 11.15 • n=4 Participants	52.6 Years STANDARD_DEVIATION 11.74 • n=21 Participants
Sex: Female, Male Female	13 Participants n=5 Participants	13 Participants n=7 Participants	10 Participants n=5 Participants	14 Participants n=4 Participants	50 Participants n=21 Participants
Sex: Female, Male Male	25 Participants n=5 Participants	29 Participants n=7 Participants	29 Participants n=5 Participants	18 Participants n=4 Participants	101 Participants n=21 Participants
World Health Organization Grading for Gliomas Grade 3	0 Participants n=5 Participants	0 Participants n=7 Participants	39 Participants n=5 Participants	0 Participants n=4 Participants	39 Participants n=21 Participants
World Health Organization Grading for Gliomas Grade 4	38 Participants n=5 Participants	42 Participants n=7 Participants	0 Participants n=5 Participants	32 Participants n=4 Participants	112 Participants n=21 Participants

PRIMARY outcome

Timeframe: At Month 6 from randomization (Cohort 1) or first day of treatment (Cohorts 2 and 3)

Population: Full Analysis Set included all participants who received at least one dose of study drug

PFS at Month 6 was defined as the percentage of participants who remained alive and progression-free at Month 6, based on investigator's assessment. Progression was defined using Response Assessment in Neuro-Oncology (RANO) criteria, as a greater than 25% increase in enhancing lesions despite stable or increasing steroid dose, an increase (significant) in non-enhancing T2-weighted-Fluid-Attenuated Inversion Recovery (T2/FLAIR) lesions that are not attributable to other non-tumor causes, and any new lesions. PFS rate at Month 6 was estimated from Kaplan-Meier (K-M) product-limit estimate of PFS.

Outcome measures

Measure	Cohort 3 - Lenvatinib n=32 Participants Participants with recurrent GBM who had disease progression following prior bevacizumab treatment; received lenvatinib capsules 24 mg taken orally, once daily continuously in 28-day cycles	Cohort 1 - Bevacizumab n=38 Participants Participants with recurrent Grade 4 malignant glioma (ie, glioblastoma \[GBM\]) who were bevacizumab-naive; received bevacizumab 10 mg/kg administered intravenously every 2 weeks in 28-day cycles	Cohort 1 - Lenvatinib n=42 Participants Participants with recurrent Grade 4 malignant glioma (ie, glioblastoma \[GBM\]) who were bevacizumab-naive; received lenvatinib capsules 24 mg taken orally, once daily continuously in 28-day cycles	Cohort 2 - Lenvatinib n=39 Participants Participants with recurrent Grade 3 malignant glioma who were bevacizumab-naive; received lenvatinib capsules 24 mg taken orally, once daily continuously in 28-day cycles
Progression Free Survival (PFS) Rate at Month 6	7.6 Percentage of participants Interval 1.3 to 21.5	11.0 Percentage of participants Interval 3.5 to 23.4	21.2 Percentage of participants Interval 10.4 to 34.5	8.0 Percentage of participants Interval 1.6 to 21.6

SECONDARY outcome

Timeframe: From date of randomization (Cohort 1) or first day of treatment (Cohorts 2 and 3) until disease progression, development of unacceptable toxicity, withdrawal of consent or up to data cutoff date of 19 March 2013 (i.e., 2.4 years)

Population: Full Analysis Set included all participants who received at least one dose of study drug

ORR was the percentage of participants with best overall response (BOR) of complete response (CR) and partial response (PR) based on RANO criteria and investigator's assessment. CR was defined as the disappearance of all enhancing disease (measurable and non-measurable) sustained for at least 4 weeks, no new lesions, and stable or improved non-enhancing (T2/FLAIR) lesions. PR was defined as greater than or equal to 50% decrease, compared to baseline, in the sum of products of perpendicular diameters of all measureable enhancing lesions sustained for at least 4 weeks. No progression of non-measurable disease, no new lesions, stable or improved non-enhancing (T2/FLAIR) lesions on same or lower dose of corticosteroids compared to baseline. For both CR and PR, in the absence of a confirming scan 4 weeks later, this scan was considered only stable disease. Only participants with measureable disease at baseline were included in evaluation of ORR.

Outcome measures

Measure	Cohort 3 - Lenvatinib n=32 Participants Participants with recurrent GBM who had disease progression following prior bevacizumab treatment; received lenvatinib capsules 24 mg taken orally, once daily continuously in 28-day cycles	Cohort 1 - Bevacizumab n=38 Participants Participants with recurrent Grade 4 malignant glioma (ie, glioblastoma \[GBM\]) who were bevacizumab-naive; received bevacizumab 10 mg/kg administered intravenously every 2 weeks in 28-day cycles	Cohort 1 - Lenvatinib n=42 Participants Participants with recurrent Grade 4 malignant glioma (ie, glioblastoma \[GBM\]) who were bevacizumab-naive; received lenvatinib capsules 24 mg taken orally, once daily continuously in 28-day cycles	Cohort 2 - Lenvatinib n=39 Participants Participants with recurrent Grade 3 malignant glioma who were bevacizumab-naive; received lenvatinib capsules 24 mg taken orally, once daily continuously in 28-day cycles
Objective Response Rate (ORR)	0.0 Percentage of participants Interval 0.0 to 10.9	15.8 Percentage of participants Interval 6.0 to 31.3	21.4 Percentage of participants Interval 10.3 to 36.8	7.7 Percentage of participants Interval 1.6 to 20.9

SECONDARY outcome

Timeframe: From date of randomization (Cohort 1) or first day of treatment (Cohorts 2 and 3) until disease progression, development of unacceptable toxicity, withdrawal of consent or up to data cutoff date of 19 March 2013 (ie, 2.4 years)

Population: Full Analysis Set - all participants who received at least one dose of study drug

PFS was measured as the time from randomization (Cohort 1) or the first day of treatment (Cohorts 2 and 3) until the date of first documentation of disease progression or date of death, if death occurred prior to disease progression, based on investigator's assessment.

Outcome measures

Measure	Cohort 3 - Lenvatinib n=32 Participants Participants with recurrent GBM who had disease progression following prior bevacizumab treatment; received lenvatinib capsules 24 mg taken orally, once daily continuously in 28-day cycles	Cohort 1 - Bevacizumab n=38 Participants Participants with recurrent Grade 4 malignant glioma (ie, glioblastoma \[GBM\]) who were bevacizumab-naive; received bevacizumab 10 mg/kg administered intravenously every 2 weeks in 28-day cycles	Cohort 1 - Lenvatinib n=42 Participants Participants with recurrent Grade 4 malignant glioma (ie, glioblastoma \[GBM\]) who were bevacizumab-naive; received lenvatinib capsules 24 mg taken orally, once daily continuously in 28-day cycles	Cohort 2 - Lenvatinib n=39 Participants Participants with recurrent Grade 3 malignant glioma who were bevacizumab-naive; received lenvatinib capsules 24 mg taken orally, once daily continuously in 28-day cycles
Progression Free Survival	1.8 Months Interval 1.0 to 2.5	2.8 Months Interval 1.9 to 3.6	2.4 Months Interval 1.8 to 3.6	2.8 Months Interval 1.9 to 3.7

SECONDARY outcome

Timeframe: From date of randomization (Cohort 1) or first day of treatment (Cohorts 2 and 3) until death due to any cause or up to data cutoff date of 19 March 2013 (ie, 2.4 years)

Population: Full Analysis Set - all participants who received at least one dose of study drug

OS was measured as the time from the randomization date (Cohort 1) or the first day of treatment (Cohort 2 and 3) to the date of death from any cause.

Outcome measures

Measure	Cohort 3 - Lenvatinib n=32 Participants Participants with recurrent GBM who had disease progression following prior bevacizumab treatment; received lenvatinib capsules 24 mg taken orally, once daily continuously in 28-day cycles	Cohort 1 - Bevacizumab n=38 Participants Participants with recurrent Grade 4 malignant glioma (ie, glioblastoma \[GBM\]) who were bevacizumab-naive; received bevacizumab 10 mg/kg administered intravenously every 2 weeks in 28-day cycles	Cohort 1 - Lenvatinib n=42 Participants Participants with recurrent Grade 4 malignant glioma (ie, glioblastoma \[GBM\]) who were bevacizumab-naive; received lenvatinib capsules 24 mg taken orally, once daily continuously in 28-day cycles	Cohort 2 - Lenvatinib n=39 Participants Participants with recurrent Grade 3 malignant glioma who were bevacizumab-naive; received lenvatinib capsules 24 mg taken orally, once daily continuously in 28-day cycles
Overall Survival (OS)	4.1 Months Interval 3.0 to 5.9	6.0 Months Interval 4.5 to 7.7	7.5 Months Interval 5.6 to 11.6	12.0 Months Interval 8.4 to NA= Not applicable as it is not evaluable.

SECONDARY outcome

Timeframe: From date of randomization (Cohort 1) or first day of treatment (Cohorts 2 and 3) until disease progression, development of unacceptable toxicity, withdrawal of consent or up to data cutoff date of 19 March 2013 (ie, 2.4 years)

Population: Full Analysis Set - all participants who received at least one dose of study drug

DCR was the percentage of the participants who had BOR of CR, PR, and stable disease (SD) with the minimum duration of SD lasting greater than or equal to 7 weeks. Only participants with measurable disease at baseline were included in evaluation of DCR, based on investigator's assessment.

Outcome measures

Measure	Cohort 3 - Lenvatinib n=32 Participants Participants with recurrent GBM who had disease progression following prior bevacizumab treatment; received lenvatinib capsules 24 mg taken orally, once daily continuously in 28-day cycles	Cohort 1 - Bevacizumab n=38 Participants Participants with recurrent Grade 4 malignant glioma (ie, glioblastoma \[GBM\]) who were bevacizumab-naive; received bevacizumab 10 mg/kg administered intravenously every 2 weeks in 28-day cycles	Cohort 1 - Lenvatinib n=42 Participants Participants with recurrent Grade 4 malignant glioma (ie, glioblastoma \[GBM\]) who were bevacizumab-naive; received lenvatinib capsules 24 mg taken orally, once daily continuously in 28-day cycles	Cohort 2 - Lenvatinib n=39 Participants Participants with recurrent Grade 3 malignant glioma who were bevacizumab-naive; received lenvatinib capsules 24 mg taken orally, once daily continuously in 28-day cycles
Disease Control Rate (DCR)	28.1 Percentage of participants Interval 13.7 to 46.7	57.9 Percentage of participants Interval 40.8 to 73.7	50.0 Percentage of participants Interval 34.2 to 65.8	48.7 Percentage of participants Interval 32.4 to 65.2

SECONDARY outcome

Timeframe: From date of randomization (Cohort 1) or first day of treatment (Cohorts 2 and 3) until disease progression, development of unacceptable toxicity, withdrawal of consent or up to data cutoff date of 19 March 2013 (ie, 2.4 years)

Population: Full Analysis Set - all participants who received at least one dose of study drug

CBR was the percentage of the participants who had BOR of CR, PR, and SD with the minimum duration of SD lasting greater than or equal to 23 weeks. Only participants with measurable disease at baseline were included in evaluation of CBR, based on investigator's assessment.

Outcome measures

Measure	Cohort 3 - Lenvatinib n=32 Participants Participants with recurrent GBM who had disease progression following prior bevacizumab treatment; received lenvatinib capsules 24 mg taken orally, once daily continuously in 28-day cycles	Cohort 1 - Bevacizumab n=38 Participants Participants with recurrent Grade 4 malignant glioma (ie, glioblastoma \[GBM\]) who were bevacizumab-naive; received bevacizumab 10 mg/kg administered intravenously every 2 weeks in 28-day cycles	Cohort 1 - Lenvatinib n=42 Participants Participants with recurrent Grade 4 malignant glioma (ie, glioblastoma \[GBM\]) who were bevacizumab-naive; received lenvatinib capsules 24 mg taken orally, once daily continuously in 28-day cycles	Cohort 2 - Lenvatinib n=39 Participants Participants with recurrent Grade 3 malignant glioma who were bevacizumab-naive; received lenvatinib capsules 24 mg taken orally, once daily continuously in 28-day cycles
Clinical Benefit Rate (CBR)	6.3 Percentage of participants Interval 0.8 to 20.8	15.8 Percentage of participants Interval 6.0 to 31.3	26.2 Percentage of participants Interval 13.9 to 42.0	17.9 Percentage of participants Interval 7.5 to 33.5

SECONDARY outcome

Timeframe: For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years)

Population: Full Analysis Set - all participants who received at least one dose of study drug

Safety was assessed by monitoring and recording all AEs including all Common Terminology Criteria for Adverse Events (CTCAE) grades (for both increasing and decreasing severity) and SAEs; regular monitoring of hematology, clinical chemistry, and urine values; results of physical examinations, regular measurement of vital signs, and electrocardiograms (ECGs), as detailed in the Schedule of Visits and Procedures. The relationship of AEs to treatment was based on investigator judgment. Details of AEs and SAEs are provided in the reported adverse event section.

Outcome measures

Measure	Cohort 3 - Lenvatinib n=32 Participants Participants with recurrent GBM who had disease progression following prior bevacizumab treatment; received lenvatinib capsules 24 mg taken orally, once daily continuously in 28-day cycles	Cohort 1 - Bevacizumab n=38 Participants Participants with recurrent Grade 4 malignant glioma (ie, glioblastoma \[GBM\]) who were bevacizumab-naive; received bevacizumab 10 mg/kg administered intravenously every 2 weeks in 28-day cycles	Cohort 1 - Lenvatinib n=42 Participants Participants with recurrent Grade 4 malignant glioma (ie, glioblastoma \[GBM\]) who were bevacizumab-naive; received lenvatinib capsules 24 mg taken orally, once daily continuously in 28-day cycles	Cohort 2 - Lenvatinib n=39 Participants Participants with recurrent Grade 3 malignant glioma who were bevacizumab-naive; received lenvatinib capsules 24 mg taken orally, once daily continuously in 28-day cycles
Number of Participants With Adverse Events (AEs)/Serious Adverse Events (SAEs) as a Measure of Safety SAEs	15 Participants	9 Participants	20 Participants	12 Participants
Number of Participants With Adverse Events (AEs)/Serious Adverse Events (SAEs) as a Measure of Safety AEs	32 Participants	38 Participants	40 Participants	39 Participants

Adverse Events

Cohort 1 - Bevacizumab

Serious events: 10 serious events

Other events: 38 other events

Deaths: 36 deaths

Cohort 1 - Lenvatinib

Serious events: 22 serious events

Other events: 40 other events

Deaths: 38 deaths

Cohort 2 - Lenvatinib

Serious events: 12 serious events

Other events: 39 other events

Deaths: 27 deaths

Cohort 3 - Lenvatinib

Serious events: 15 serious events

Other events: 31 other events

Deaths: 30 deaths

Serious adverse events

Measure	Cohort 1 - Bevacizumab n=38 participants at risk Participants with recurrent Grade 4 malignant glioma (ie, glioblastoma \[GBM\]) who were bevacizumab-naive; received bevacizumab 10 mg/kg administered intravenously every 2 weeks in 28-day cycles	Cohort 1 - Lenvatinib n=42 participants at risk Participants with recurrent Grade 4 malignant glioma (ie, glioblastoma \[GBM\]) who were bevacizumab-naive; received lenvatinib capsules 24 mg taken orally, once daily continuously in 28-day cycles	Cohort 2 - Lenvatinib n=39 participants at risk Participants with recurrent Grade 3 malignant glioma who were bevacizumab-naive; received lenvatinib capsules 24 mg taken orally, once daily continuously in 28-day cycles	Cohort 3 - Lenvatinib n=32 participants at risk Participants with recurrent GBM who had disease progression following prior bevacizumab treatment; received lenvatinib capsules 24 mg taken orally, once daily continuously in 28-day cycles
Cardiac disorders Myocardial infarction	0.00% 0/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	2.6% 1/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Cardiac disorders Tachycardia	0.00% 0/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	2.6% 1/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Endocrine disorders Hypothyroidism	0.00% 0/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	4.8% 2/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Gastrointestinal disorders Abdominal pain	2.6% 1/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	3.1% 1/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Gastrointestinal disorders Intestinal perforation	0.00% 0/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	2.4% 1/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Gastrointestinal disorders Large intestine perforation	0.00% 0/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	2.4% 1/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Gastrointestinal disorders Nausea	0.00% 0/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	2.4% 1/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	2.6% 1/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	3.1% 1/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Gastrointestinal disorders Pancreatitis	0.00% 0/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	3.1% 1/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Gastrointestinal disorders Vomiting	0.00% 0/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	4.8% 2/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	3.1% 1/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
General disorders Asthenia	0.00% 0/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	2.4% 1/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	2.6% 1/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
General disorders Fatigue	0.00% 0/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	5.1% 2/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
General disorders General physical health deterioration	0.00% 0/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	4.8% 2/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
General disorders Pyrexia	0.00% 0/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	2.4% 1/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Hepatobiliary disorders Cholecystitis	0.00% 0/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	2.4% 1/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	3.1% 1/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Hepatobiliary disorders Hepatitis acute	0.00% 0/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	2.4% 1/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Infections and infestations Bacteraemia	0.00% 0/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	3.1% 1/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Infections and infestations Cellulitis	0.00% 0/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	2.6% 1/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	3.1% 1/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Infections and infestations Diverticulitis	0.00% 0/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	2.6% 1/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Infections and infestations Perirectal abscess	0.00% 0/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	3.1% 1/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Infections and infestations Pneumonia	5.3% 2/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	3.1% 1/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Infections and infestations Skin infection	0.00% 0/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	2.4% 1/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Infections and infestations Urosepsis	0.00% 0/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	3.1% 1/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Injury, poisoning and procedural complications Thermal burn	0.00% 0/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	2.4% 1/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Injury, poisoning and procedural complications Wound dehiscence	5.3% 2/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Investigations Alanine aminotransferase increased	0.00% 0/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	2.6% 1/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Investigations Lipase increased	0.00% 0/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	2.4% 1/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Metabolism and nutrition disorders Dehydration	0.00% 0/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	2.6% 1/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	3.1% 1/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Metabolism and nutrition disorders Hyperglycaemia	2.6% 1/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	2.6% 1/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Metabolism and nutrition disorders Hyperkalaemia	0.00% 0/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	3.1% 1/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	2.4% 1/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Musculoskeletal and connective tissue disorders Muscular weakness	2.6% 1/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	2.4% 1/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	2.6% 1/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Musculoskeletal and connective tissue disorders Myopathy	2.6% 1/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant neoplasm progression	0.00% 0/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	3.1% 1/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Nervous system disorders Hemianopia homonymous	0.00% 0/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	2.4% 1/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour haemorrhage	0.00% 0/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	2.4% 1/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Nervous system disorders Cerebrovascular accident	0.00% 0/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	4.8% 2/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Nervous system disorders Cognitive disorder	2.6% 1/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Nervous system disorders Convulsion	5.3% 2/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	11.9% 5/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	2.6% 1/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	6.2% 2/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Nervous system disorders Depressed level of consciousness	0.00% 0/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	2.4% 1/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	2.6% 1/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Nervous system disorders Encephalopathy	0.00% 0/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	3.1% 1/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Nervous system disorders Haemorrhage intracranial	0.00% 0/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	3.1% 1/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Nervous system disorders Haemorrhagic stroke	2.6% 1/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Nervous system disorders Headache	0.00% 0/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	2.4% 1/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	5.1% 2/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Nervous system disorders Hemiparesis	0.00% 0/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	3.1% 1/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Nervous system disorders Peripheral motor neuropathy	2.6% 1/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	3.1% 1/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Nervous system disorders Pyramidal tract syndrome	0.00% 0/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	2.6% 1/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Nervous system disorders Somnolence	0.00% 0/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	2.6% 1/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Nervous system disorders Subarachnoid haemorrhage	0.00% 0/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	2.6% 1/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Psychiatric disorders Agitation	0.00% 0/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	2.6% 1/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Psychiatric disorders Confusional state	0.00% 0/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	2.6% 1/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	3.1% 1/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Psychiatric disorders Delirium	0.00% 0/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	3.1% 1/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Psychiatric disorders Depressed mood	0.00% 0/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	2.4% 1/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	3.1% 1/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	2.4% 1/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Vascular disorders Embolism	0.00% 0/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	3.1% 1/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Vascular disorders Hypertension	2.6% 1/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	2.6% 1/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	3.1% 1/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Vascular disorders Hypotension	0.00% 0/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	3.1% 1/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Gastrointestinal disorders Rectal Hemorrhage	0.00% 0/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	2.4% 1/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Nervous system disorders Ischaemic stroke	2.6% 1/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.

Other adverse events

Measure	Cohort 1 - Bevacizumab n=38 participants at risk Participants with recurrent Grade 4 malignant glioma (ie, glioblastoma \[GBM\]) who were bevacizumab-naive; received bevacizumab 10 mg/kg administered intravenously every 2 weeks in 28-day cycles	Cohort 1 - Lenvatinib n=42 participants at risk Participants with recurrent Grade 4 malignant glioma (ie, glioblastoma \[GBM\]) who were bevacizumab-naive; received lenvatinib capsules 24 mg taken orally, once daily continuously in 28-day cycles	Cohort 2 - Lenvatinib n=39 participants at risk Participants with recurrent Grade 3 malignant glioma who were bevacizumab-naive; received lenvatinib capsules 24 mg taken orally, once daily continuously in 28-day cycles	Cohort 3 - Lenvatinib n=32 participants at risk Participants with recurrent GBM who had disease progression following prior bevacizumab treatment; received lenvatinib capsules 24 mg taken orally, once daily continuously in 28-day cycles
Blood and lymphatic system disorders Anaemia	5.3% 2/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	4.8% 2/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	6.2% 2/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Blood and lymphatic system disorders Thrombocytopenia	2.6% 1/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	2.4% 1/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	5.1% 2/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	18.8% 6/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Cardiac disorders Sinus tachycardia	5.3% 2/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	2.4% 1/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Cardiac disorders Splinter haemorrhages	0.00% 0/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	5.1% 2/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Ear and labyrinth disorders Ear discomfort	5.3% 2/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	2.6% 1/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Ear and labyrinth disorders Hypoacusis	0.00% 0/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	6.2% 2/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Endocrine disorders Hypothyroidism	2.6% 1/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	16.7% 7/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	25.6% 10/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	12.5% 4/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Gastrointestinal disorders Abdominal discomfort	0.00% 0/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	5.1% 2/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	3.1% 1/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Gastrointestinal disorders Abdominal distension	2.6% 1/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	5.1% 2/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Gastrointestinal disorders Abdominal pain	0.00% 0/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	7.7% 3/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Gastrointestinal disorders Abdominal pain upper	7.9% 3/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	9.5% 4/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	2.6% 1/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	9.4% 3/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Gastrointestinal disorders Constipation	15.8% 6/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	16.7% 7/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	23.1% 9/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	18.8% 6/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Gastrointestinal disorders Diarrhoea	18.4% 7/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	16.7% 7/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	28.2% 11/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	31.2% 10/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Gastrointestinal disorders Dry mouth	0.00% 0/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	2.4% 1/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	5.1% 2/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Gastrointestinal disorders Dyspepsia	7.9% 3/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	9.5% 4/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	2.6% 1/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	9.4% 3/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Gastrointestinal disorders Dysphagia	5.3% 2/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	7.1% 3/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	5.1% 2/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	15.6% 5/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Gastrointestinal disorders Faecal incontinence	7.9% 3/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	2.4% 1/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	3.1% 1/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Gastrointestinal disorders Flatulence	2.6% 1/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	2.4% 1/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	5.1% 2/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Gastrointestinal disorders Gastrooesophageal reflux disease	7.9% 3/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	9.5% 4/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	2.6% 1/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	12.5% 4/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Gastrointestinal disorders Gingival bleeding	2.6% 1/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	2.4% 1/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	6.2% 2/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Gastrointestinal disorders Haemorrhoids	0.00% 0/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	2.6% 1/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	6.2% 2/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Gastrointestinal disorders Mouth ulceration	2.6% 1/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	5.1% 2/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	3.1% 1/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Gastrointestinal disorders Nausea	26.3% 10/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	14.3% 6/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	20.5% 8/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	15.6% 5/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Gastrointestinal disorders Oral pain	2.6% 1/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	4.8% 2/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	7.7% 3/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Gastrointestinal disorders Stomatitis	7.9% 3/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	11.9% 5/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	15.4% 6/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	15.6% 5/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Gastrointestinal disorders Tongue ulceration	0.00% 0/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	5.1% 2/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	3.1% 1/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Gastrointestinal disorders Vomiting	2.6% 1/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	7.1% 3/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	10.3% 4/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	3.1% 1/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
General disorders Asthenia	2.6% 1/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	2.4% 1/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	2.6% 1/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	6.2% 2/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
General disorders Fatigue	55.3% 21/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	59.5% 25/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	64.1% 25/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	43.8% 14/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
General disorders Feeling cold	0.00% 0/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	6.2% 2/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
General disorders Gait disturbance	13.2% 5/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	11.9% 5/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	2.6% 1/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	6.2% 2/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
General disorders Irritability	5.3% 2/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	2.4% 1/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	2.6% 1/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
General disorders Non-cardiac chest pain	0.00% 0/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	7.1% 3/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
General disorders Oedema peripheral	7.9% 3/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	11.9% 5/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	5.1% 2/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	6.2% 2/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Infections and infestations Candida infection	2.6% 1/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	2.4% 1/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	2.6% 1/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	6.2% 2/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Infections and infestations Nasopharyngitis	5.3% 2/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	2.4% 1/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Infections and infestations Oral candidiasis	0.00% 0/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	7.1% 3/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	2.6% 1/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Infections and infestations Sinusitis	5.3% 2/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	2.4% 1/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	6.2% 2/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Infections and infestations Tooth infection	2.6% 1/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	5.1% 2/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Infections and infestations Upper respiratory tract infection	5.3% 2/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	4.8% 2/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	3.1% 1/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Infections and infestations Urinary tract infection	10.5% 4/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	14.3% 6/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	2.6% 1/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	12.5% 4/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Injury, poisoning and procedural complications Contusion	13.2% 5/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	4.8% 2/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	5.1% 2/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	3.1% 1/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Injury, poisoning and procedural complications Fall	2.6% 1/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	2.4% 1/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	10.3% 4/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	3.1% 1/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Investigations Alanine aminotransferase increased	0.00% 0/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	4.8% 2/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	12.8% 5/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	6.2% 2/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Investigations Aspartate aminotransferase increased	0.00% 0/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	4.8% 2/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	2.6% 1/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	6.2% 2/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Investigations Blood pressure increased	7.9% 3/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	4.8% 2/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	5.1% 2/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	6.2% 2/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Investigations Lipase increased	0.00% 0/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	2.4% 1/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	5.1% 2/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	6.2% 2/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Investigations Platelet count decreased	5.3% 2/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	9.5% 4/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	5.1% 2/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	12.5% 4/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Investigations Weight decreased	2.6% 1/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	7.1% 3/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	7.7% 3/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	6.2% 2/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Metabolism and nutrition disorders Decreased appetite	7.9% 3/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	21.4% 9/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	15.4% 6/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	9.4% 3/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Metabolism and nutrition disorders Dehydration	0.00% 0/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	4.8% 2/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	7.7% 3/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	3.1% 1/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Metabolism and nutrition disorders Hyperglycaemia	13.2% 5/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	16.7% 7/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	10.3% 4/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	6.2% 2/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Metabolism and nutrition disorders Hypoalbuminaemia	2.6% 1/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	9.5% 4/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	9.4% 3/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Metabolism and nutrition disorders Hypocalcaemia	2.6% 1/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	7.1% 3/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	12.5% 4/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	2.4% 1/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	9.4% 3/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Metabolism and nutrition disorders Hypophosphataemia	2.6% 1/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	2.4% 1/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	5.1% 2/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	9.4% 3/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Musculoskeletal and connective tissue disorders Arthralgia	10.5% 4/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	11.9% 5/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	12.8% 5/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	15.6% 5/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Musculoskeletal and connective tissue disorders Back pain	2.6% 1/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	19.0% 8/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	5.1% 2/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	3.1% 1/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Musculoskeletal and connective tissue disorders Muscle spasms	2.6% 1/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	2.4% 1/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	7.7% 3/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	3.1% 1/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Musculoskeletal and connective tissue disorders Muscular weakness	10.5% 4/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	19.0% 8/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	25.6% 10/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	12.5% 4/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	5.3% 2/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	2.6% 1/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	5.3% 2/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	2.4% 1/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	10.3% 4/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	4.8% 2/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	17.9% 7/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	9.4% 3/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	5.1% 2/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Musculoskeletal and connective tissue disorders Pain in extremity	13.2% 5/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	9.5% 4/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	7.7% 3/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	3.1% 1/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Nervous system disorders Aphasia	23.7% 9/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	9.5% 4/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	5.1% 2/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	15.6% 5/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Nervous system disorders Ataxia	15.8% 6/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	7.1% 3/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	12.5% 4/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Nervous system disorders Balance disorder	0.00% 0/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	7.7% 3/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	6.2% 2/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Nervous system disorders Cognitive disorder	0.00% 0/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	2.6% 1/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	9.4% 3/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Nervous system disorders Convulsion	5.3% 2/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	7.1% 3/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	5.1% 2/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	12.5% 4/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Nervous system disorders Disturbance in attention	0.00% 0/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	7.1% 3/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Nervous system disorders Dizziness	7.9% 3/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	16.7% 7/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	7.7% 3/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	6.2% 2/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Nervous system disorders Dysarthria	2.6% 1/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	2.6% 1/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	6.2% 2/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Nervous system disorders Dysgeusia	0.00% 0/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	7.1% 3/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	2.6% 1/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	3.1% 1/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Nervous system disorders Headache	34.2% 13/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	14.3% 6/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	30.8% 12/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	40.6% 13/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Nervous system disorders Hemianopia homonymous	5.3% 2/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	2.4% 1/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Nervous system disorders Hemiparesis	10.5% 4/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	9.5% 4/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	7.7% 3/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	9.4% 3/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Nervous system disorders Hypoaesthesia	15.8% 6/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	2.4% 1/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	7.7% 3/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	6.2% 2/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Nervous system disorders Memory impairment	13.2% 5/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	4.8% 2/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	10.3% 4/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	3.1% 1/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Nervous system disorders Paraesthesia	10.5% 4/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	9.5% 4/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	5.1% 2/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	12.5% 4/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Nervous system disorders Partial seizures	0.00% 0/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	6.2% 2/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Nervous system disorders Peripheral motor neuropathy	7.9% 3/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	6.2% 2/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Nervous system disorders Pyramidal tract syndrome	7.9% 3/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	2.4% 1/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Nervous system disorders Tremor	0.00% 0/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	2.4% 1/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	10.3% 4/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	3.1% 1/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Psychiatric disorders Agitation	15.8% 6/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	7.1% 3/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	6.2% 2/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Psychiatric disorders Anxiety	5.3% 2/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	4.8% 2/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	10.3% 4/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	9.4% 3/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Psychiatric disorders Confusional state	18.4% 7/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	7.1% 3/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	12.8% 5/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	18.8% 6/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Psychiatric disorders Depression	15.8% 6/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	4.8% 2/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	7.7% 3/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	12.5% 4/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Psychiatric disorders Flat affect	5.3% 2/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Psychiatric disorders Insomnia	5.3% 2/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	11.9% 5/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	20.5% 8/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	6.2% 2/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Psychiatric disorders Mood swings	0.00% 0/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	6.2% 2/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Renal and urinary disorders Glycosuria	5.3% 2/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	2.6% 1/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Renal and urinary disorders Pollakiuria	5.3% 2/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	2.4% 1/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	5.1% 2/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	3.1% 1/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Renal and urinary disorders Proteinuria	5.3% 2/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	14.3% 6/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	10.3% 4/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	28.1% 9/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Renal and urinary disorders Urinary incontinence	7.9% 3/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	9.5% 4/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	10.3% 4/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	6.2% 2/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Respiratory, thoracic and mediastinal disorders Cough	5.3% 2/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	5.1% 2/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	3.1% 1/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Respiratory, thoracic and mediastinal disorders Dysphonia	10.5% 4/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	33.3% 14/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	28.2% 11/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	28.1% 9/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Respiratory, thoracic and mediastinal disorders Dyspnoea	10.5% 4/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	16.7% 7/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	6.2% 2/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	5.3% 2/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	2.4% 1/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Respiratory, thoracic and mediastinal disorders Epistaxis	7.9% 3/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	9.5% 4/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	2.6% 1/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	12.5% 4/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Respiratory, thoracic and mediastinal disorders Hiccups	5.3% 2/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	4.8% 2/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	7.7% 3/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	6.2% 2/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	2.6% 1/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	7.1% 3/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Respiratory, thoracic and mediastinal disorders Painful respiration	0.00% 0/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	6.2% 2/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Skin and subcutaneous tissue disorders Acne	0.00% 0/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	5.1% 2/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	3.1% 1/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Skin and subcutaneous tissue disorders Alopecia	5.3% 2/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	2.4% 1/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	2.6% 1/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	3.1% 1/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Skin and subcutaneous tissue disorders Dermatitis	0.00% 0/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	5.1% 2/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Skin and subcutaneous tissue disorders Dermatitis acneiform	0.00% 0/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	5.1% 2/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Skin and subcutaneous tissue disorders Drug eruption	2.6% 1/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	5.1% 2/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Skin and subcutaneous tissue disorders Dry skin	0.00% 0/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	2.4% 1/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	5.1% 2/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Skin and subcutaneous tissue disorders Ecchymosis	0.00% 0/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	7.1% 3/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Skin and subcutaneous tissue disorders Hyperhidrosis	10.5% 4/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	4.8% 2/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	5.1% 2/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	9.4% 3/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Skin and subcutaneous tissue disorders Hyperkeratosis	0.00% 0/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	5.1% 2/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Skin and subcutaneous tissue disorders Night sweats	2.6% 1/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	5.1% 2/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysaesthesia syndrome	0.00% 0/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	2.4% 1/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	7.7% 3/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	9.4% 3/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Skin and subcutaneous tissue disorders Rash	10.5% 4/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	7.1% 3/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	10.3% 4/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	6.2% 2/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Vascular disorders Deep vein thrombosis	5.3% 2/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	2.6% 1/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	0.00% 0/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.
Vascular disorders Hypertension	36.8% 14/38 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	50.0% 21/42 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	43.6% 17/39 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.	46.9% 15/32 • For each participant, from the first patient first dose till 30 days after the last dose or the cut-off date of 19 March 2013 (ie, 2.4 years) All participants were followed for survival until death, except where a participant withdrew consent, or the Sponsor stopped the survival follow-up during the extension phase after completion of the primary study analysis. Since death was not a protocol defined reason for non-completion, the all cause mortality data below are not reflected in the Participant Flow section.

Additional Information

Eisai Medical Services

Eisai, Inc.

Phone: 1-888-422-4743

Email: esi_medinfo@eisai.com

Results disclosure agreements

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

Restriction type: OTHER