Trial Outcomes & Findings for A Study of Single-Agent Eribulin Mesylate as First-Line Therapy for Locally Recurrent or Metastatic Human Epidermal Growth Factor Receptor Two (HER2) Negative Breast Cancer (NCT NCT01268150)

Last Updated: 2023-06-22

Results Overview

The ORR was defined as the percentage of participants with best overall response (BOR) of confirmed complete response (CR) or partial response (PR), based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Targeted lesions were assessed by computed tomography (CT) and magnetic resonance imaging (MRI) which were then assessed by the investigator based on RECIST. CR was defined as the disappearance of all target lesions. PR was defined as at least 30% decrease in the sum of diameters of target lesions, taking as reference baseline sum diameters. Possible CR and PR had to be confirmed no fewer than 4 weeks after the initial response assessment. A brain and bone scan was performed by CT/MRI within 1 week after confirmation of a response to ensure no new metastases. To be assigned a status of CR or PR, changes in tumor measurements had to be confirmed by repeat evaluations, to be performed not fewer than 4 weeks after the response criteria were first met. ORR = CR + PR

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

56 participants

Primary outcome timeframe

Cycle 1 (Day 1) until first evidence of disease progression, assessed up to the data cutoff date (30 Aug 2013) up to 2.5 years

Results posted on

2023-06-22

Participant Flow

Participant milestones

Participant milestones
Measure	Eribulin Mesylate Eribulin mesylate at 1.4 mg/m\^2 was administered as an intravenous (IV) infusion over 2 to 5 minutes on Days 1 and 8 of each 3-week cycle.
Treatment Phase STARTED	56
Treatment Phase COMPLETED	28
Treatment Phase NOT COMPLETED	28
Extension Phase STARTED	28
Extension Phase Treatment Ongoing at Data Cutoff Date	1
Extension Phase COMPLETED	1
Extension Phase NOT COMPLETED	27

Reasons for withdrawal

Reasons for withdrawal
Measure	Eribulin Mesylate Eribulin mesylate at 1.4 mg/m\^2 was administered as an intravenous (IV) infusion over 2 to 5 minutes on Days 1 and 8 of each 3-week cycle.
Treatment Phase Progression of disease	18
Treatment Phase Adverse Event	3
Treatment Phase Withdrawal by Subject	3
Treatment Phase Other	4
Extension Phase Adverse Event	3
Extension Phase Disease progression	18
Extension Phase Other	6

Baseline Characteristics

A Study of Single-Agent Eribulin Mesylate as First-Line Therapy for Locally Recurrent or Metastatic Human Epidermal Growth Factor Receptor Two (HER2) Negative Breast Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Eribulin Mesylate n=56 Participants Eribulin mesylate at 1.4 mg/m\^2 was administered as an intravenous (IV) infusion over 2 to 5 minutes on Days 1 and 8 of each 3-week cycle.
Age, Continuous	57.0 Years STANDARD_DEVIATION 10.78 • n=5 Participants
Sex: Female, Male Female	56 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Cycle 1 (Day 1) until first evidence of disease progression, assessed up to the data cutoff date (30 Aug 2013) up to 2.5 years

Population: Full analysis set included all participants who received at least one dose of eribulin mesylate.

Outcome measures

Outcome measures
Measure	Eribulin Mesylate n=56 Participants Eribulin mesylate at 1.4 mg/m\^2 was administered as an intravenous (IV) infusion over 2 to 5 minutes on Days 1 and 8 of each 3-week cycle.
Objective Response Rate (ORR)	28.6 Percentage of participants

SECONDARY outcome

Timeframe: Treatment Phase (Day 1 Cycle 1) to earliest date of confirmed objective response (CR or PR), assessed up to the data cutoff date (30 Aug 2013) up to 2.5 years

Population: Full analysis set included all participants who received at least one dose of eribulin mesylate and were determined to be responders (CR or PR) to study treatment.

Time to first response was defined for participants whose BOR was a CR or PR. Analysis was based on the Kaplan-Meier estimated number of months to CR or PR. This statistical analysis method measures the effect of study drug on CR or PR.

Outcome measures

Outcome measures
Measure	Eribulin Mesylate n=16 Participants Eribulin mesylate at 1.4 mg/m\^2 was administered as an intravenous (IV) infusion over 2 to 5 minutes on Days 1 and 8 of each 3-week cycle.
Time to First Response (CR or PR)	1.4 Months Interval 1.22 to 2.66

SECONDARY outcome

Timeframe: First date of CR or PR to PD or Death from any cause, assessed up to the data cutoff date (30 Aug 2013) up to 2.5 years

Population: Full analysis set included all participants who received at least one dose of eribulin mesylate and were determined to be responders (CR or PR) to study treatment.

Duration of response was measured for participants who were responders only, had attained a BOR that was CR or PR. The duration of response was measured from time that response criteria for CR or PR (whichever was recorded first) were first met until the date that progressive disease (PD) or death from any cause was first objectively documented. Participants who did not have PD were censored on the day of their last tumor assessment. Duration of response was summarized for the responders using Kaplan-Meier estimation method. This statistical analysis method measures the effect of study drug on the length of response time.

Outcome measures

Outcome measures
Measure	Eribulin Mesylate n=16 Participants Eribulin mesylate at 1.4 mg/m\^2 was administered as an intravenous (IV) infusion over 2 to 5 minutes on Days 1 and 8 of each 3-week cycle.
Duration of Response	5.8 Months Interval 4.67 to 10.55

SECONDARY outcome

Timeframe: Treatment Phase (Day 1 Cycle 1) to date of progressive disease or death, whichever occurred first, assessed up to the data cutoff date (30 Aug 2013) up to 2.5 years

Population: Full analysis set included all participants who received at least one dose of eribulin mesylate.

PFS was defined as the time from the date of the first dose of study drug until the date of first documentation of PD or date of death from any cause, whichever occurred first. Participants who died without reported PD were considered to have progressed on the day of their death. Participants who were lost to follow-up or alive and without reported PD at the end of study were censored on the date of their last tumor assessment. Participants without evidence of PD upon discontinuation of study drug during the Extension Phase returned to the clinic for disease evaluation and PFS calculation every 12 weeks until PD was documented. PFS was analyzed using Kaplan-Meier product-limit estimates. This statistical analysis method measures the effect of study drug on PFS.

Outcome measures

Outcome measures
Measure	Eribulin Mesylate n=56 Participants Eribulin mesylate at 1.4 mg/m\^2 was administered as an intravenous (IV) infusion over 2 to 5 minutes on Days 1 and 8 of each 3-week cycle.
Progression-Free Survival (PFS)	6.8 Months Interval 4.44 to 7.59

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline until End of Treatment (within 21 days of last dose), assessed up to the data cutoff date (30 Aug 2013) up to 2.5 years

Population: Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment.

Treatment-emergent adverse events (TEAEs) were defined as AEs that emerged during treatment, having been absent at pretreatment, and occurring within 30 days of the last dose of study treatment, or if they were present prior to the first dose administration and increased in severity during the study. For each AE a participant with two or more TEAEs in that category were counted only once. TEAEs were considered related if the relationship of the event to study drug was possibly or probably related. Serious adverse events (SAEs) were defined as any untoward medical experience that resulted in death, was life-threatening, required hospitalization or prolongation of hospitalization, persistent or significant disability/incapacity, or was a congenital anomaly/birth defect. Safety information will be summarized with adverse events. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.

Outcome measures

Outcome measures
Measure	Eribulin Mesylate n=56 Participants Eribulin mesylate at 1.4 mg/m\^2 was administered as an intravenous (IV) infusion over 2 to 5 minutes on Days 1 and 8 of each 3-week cycle.
To Assess the Incidence of Adverse Events (AEs) of Eribulin Mesylate TEAEs	100.0 Percentage of participants
To Assess the Incidence of Adverse Events (AEs) of Eribulin Mesylate Treatment-related TEAEs	100.0 Percentage of participants
To Assess the Incidence of Adverse Events (AEs) of Eribulin Mesylate Serious TEAEs	30.4 Percentage of participants
To Assess the Incidence of Adverse Events (AEs) of Eribulin Mesylate Treatment-related Serious TEAEs	8.9 Percentage of participants
To Assess the Incidence of Adverse Events (AEs) of Eribulin Mesylate TEAEs leading to withdrawl of study drug	10.7 Percentage of participants
To Assess the Incidence of Adverse Events (AEs) of Eribulin Mesylate TEAEs leading to dose reduction	35.7 Percentage of participants

Adverse Events

Eribulin Mesylate

Serious events: 17 serious events

Other events: 56 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Eribulin Mesylate n=56 participants at risk Eribulin mesylate at 1.4 mg/m\^2 was administered as an intravenous (IV) infusion over 2 to 5 minutes on Days 1 and 8 of each 3-week cycle.
Blood and lymphatic system disorders Febrile neutropenia	5.4% 3/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Blood and lymphatic system disorders Leukopenia	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Blood and lymphatic system disorders Neutropenia	5.4% 3/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Cardiac disorders Pericardial effusion	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Cardiac disorders Supraventricular tachycardia	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Gastrointestinal disorders Intestinal perforation	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Gastrointestinal disorders Small intestinal obstruction	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Infections and infestations Bronchitis	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Infections and infestations Pyelonephritis	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Infections and infestations Sepsis	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Infections and infestations Urinary tract infection	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Injury, poisoning and procedural complications Femur fracture	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Metabolism and nutrition disorders Dehydration	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Metabolism and nutrition disorders Hypovolaemia	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Musculoskeletal and connective tissue disorders Muscular weakness	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Musculoskeletal and connective tissue disorders Pathological fracture	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bone neoplasm	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Nervous system disorders Convulsion	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Nervous system disorders Headache	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Nervous system disorders Spinal cord paralysis	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Psychiatric disorders Mental status changes	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Respiratory, thoracic and mediastinal disorders Pleural effusion	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	3.6% 2/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.

Other adverse events

Other adverse events
Measure	Eribulin Mesylate n=56 participants at risk Eribulin mesylate at 1.4 mg/m\^2 was administered as an intravenous (IV) infusion over 2 to 5 minutes on Days 1 and 8 of each 3-week cycle.
Blood and lymphatic system disorders Anaemia	37.5% 21/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Blood and lymphatic system disorders Febrile neutropenia	7.1% 4/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Blood and lymphatic system disorders Leukopenia	33.9% 19/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Blood and lymphatic system disorders Lymphadenopathy	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Blood and lymphatic system disorders Lymphopenia	8.9% 5/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Blood and lymphatic system disorders Neutropenia	71.4% 40/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Blood and lymphatic system disorders Thrombocytopenia	5.4% 3/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Cardiac disorders Angina Pectoris	3.6% 2/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Cardiac disorders Electrocardiogram QT prolonged	3.6% 2/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Cardiac disorders Palpitations	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Cardiac disorders Pericardial effusion	3.6% 2/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Cardiac disorders Sinus tachycardia	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Cardiac disorders Supraventricular tachycardia	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Ear and labyrinth disorders Ear Pain	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Ear and labyrinth disorders Eustachian tube dysfunction	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Ear and labyrinth disorders Middle ear effusion	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Ear and labyrinth disorders Tinnitus	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Eye disorders Abnormal sensation in eye	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Eye disorders Cataract	5.4% 3/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Eye disorders Dry Eye	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Eye disorders Lacrimation increased	12.5% 7/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Eye disorders Visual Impairment	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Gastrointestinal disorders Abdominal distension	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Gastrointestinal disorders Abdominal Pain	8.9% 5/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Gastrointestinal disorders Abdominal Pain Lower	3.6% 2/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Gastrointestinal disorders Abdominal pain upper	7.1% 4/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Gastrointestinal disorders Anal haemorrhage	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Gastrointestinal disorders Aphthous stomatitis	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Gastrointestinal disorders Ascites	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Gastrointestinal disorders Constipation	35.7% 20/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Gastrointestinal disorders Dental caries	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Gastrointestinal disorders Diarrhoea	33.9% 19/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Gastrointestinal disorders Diverticulum intestinal	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Gastrointestinal disorders Dry mouth	10.7% 6/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Gastrointestinal disorders Dyspepsia	8.9% 5/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Gastrointestinal disorders Food poisoning	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Gastrointestinal disorders Frequent bowel movements	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Gastrointestinal disorders Gastrooesophageal reflux disease	3.6% 2/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Gastrointestinal disorders Haemorrhoidal haemorrhage	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Gastrointestinal disorders Haemorrhoids	5.4% 3/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Gastrointestinal disorders Hypoaesthesia oral	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Gastrointestinal disorders Intestinal perforation	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Gastrointestinal disorders Lip dry	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Gastrointestinal disorders Nausea	58.9% 33/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Gastrointestinal disorders Oral disorder	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Gastrointestinal disorders Paraesthesia oral	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Gastrointestinal disorders Rectal fissure	3.6% 2/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Gastrointestinal disorders Rectal haemorrhage	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Gastrointestinal disorders Salivary gland enlargement	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Gastrointestinal disorders Salivary gland mass	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Gastrointestinal disorders Small intestinal obstruction	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Gastrointestinal disorders Stomatitis	10.7% 6/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Gastrointestinal disorders Tongue discolouration	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Gastrointestinal disorders Tooth deposit	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Gastrointestinal disorders Vomiting	25.0% 14/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
General disorders Asthenia	5.4% 3/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
General disorders Axillary pain	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
General disorders Catheter site erythema	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
General disorders Catheter site inflammation	3.6% 2/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
General disorders Catheter site pain	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
General disorders Catheter site rash	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
General disorders Chills	3.6% 2/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
General disorders Fatigue	64.3% 36/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
General disorders Gait disturbance	3.6% 2/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
General disorders Inflammation	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
General disorders Influenza like illness	3.6% 2/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
General disorders Mucosal inflammation	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
General disorders Non-cardiac chest pain	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
General disorders Oedema Peripheral	19.6% 11/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
General disorders Pain	3.6% 2/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
General disorders Pyrexia	17.9% 10/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Hepatobiliary disorders Hyperbilirubinaemia	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Immune system disorders Seasonal allergy	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Infections and infestations Abdominal abscess	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Infections and infestations Acute sinusitis	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Infections and infestations Bronchitis	3.6% 2/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Infections and infestations Candidiadis	3.6% 2/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Infections and infestations Catheter Site infection	3.6% 2/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Infections and infestations Cellulitis	3.6% 2/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Infections and infestations Diverticulitis	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Infections and infestations Gastroenteritis	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Infections and infestations Localised infection	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Infections and infestations Mastoiditis	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Infections and infestations Oral candidiasis	3.6% 2/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Infections and infestations Oral herpes	3.6% 2/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Infections and infestations Pleural infection	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Infections and infestations Pneumonia	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Infections and infestations Pyelonephritis	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Infections and infestations Sepsis	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Infections and infestations Sinusitis	10.7% 6/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Infections and infestations Upper respiratory tract infection	5.4% 3/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Infections and infestations Urinary tract infection	19.6% 11/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Infections and infestations Vaginal infection	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Infections and infestations Vulvovaginal candidiasis	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Infections and infestations Vulvovaginal mycotic infection	3.6% 2/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Injury, poisoning and procedural complications Arthropod bite	3.6% 2/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Injury, poisoning and procedural complications Contusion	3.6% 2/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Injury, poisoning and procedural complications Fall	5.4% 3/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Injury, poisoning and procedural complications Femur fracture	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Injury, poisoning and procedural complications Foot fracture	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Injury, poisoning and procedural complications Joint injury	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Injury, poisoning and procedural complications Laceration	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Injury, poisoning and procedural complications Procedural pain	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Injury, poisoning and procedural complications Thermal burn	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Injury, poisoning and procedural complications Tooth fracture	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Injury, poisoning and procedural complications Vascular access complication	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Investigations Alanine aminotransferase increased	3.6% 2/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Investigations Aspartate aminotransferase increased	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Investigations Blood alkaline phosphatase increased	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Investigations Blood creatinine increased	3.6% 2/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Investigations Blood glucose increased	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Investigations Blood phosphorus decreased	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Investigations Haemoglobin decreased	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Investigations Helicobacter test positive	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Investigations International normalised ratio increased	3.6% 2/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Investigations Liver function test abnormal	3.6% 2/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Investigations Lymphocyte count decreased	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Investigations Platelet count increased	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Investigations Prothrombin time prolonged	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Investigations Weight decreased	16.1% 9/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Investigations Weight increased	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Investigations White blood cell count decreased	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Investigations White blood cell count increased	3.6% 2/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Metabolism and nutrition disorders Decreased appetite	26.8% 15/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Metabolism and nutrition disorders Dehydration	3.6% 2/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Metabolism and nutrition disorders Diabetes mellitus	3.6% 2/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Metabolism and nutrition disorders Fluid retention	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Metabolism and nutrition disorders Hyperglycaemia	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Metabolism and nutrition disorders Hyperphosphataemia	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Metabolism and nutrition disorders Hypoalbuminaemia	7.1% 4/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Metabolism and nutrition disorders Hypocalcaemia	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Metabolism and nutrition disorders Hypokalaemia	14.3% 8/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Metabolism and nutrition disorders Hypomagnesaemia	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Metabolism and nutrition disorders Hyponatraemia	3.6% 2/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Metabolism and nutrition disorders Hypophosphataemia	3.6% 2/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Metabolism and nutrition disorders Hypovolaemia	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Musculoskeletal and connective tissue disorders Arthralgia	14.3% 8/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Musculoskeletal and connective tissue disorders Back pain	19.6% 11/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Musculoskeletal and connective tissue disorders Bone pain	8.9% 5/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Musculoskeletal and connective tissue disorders Bunion	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Musculoskeletal and connective tissue disorders Groin pain	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Musculoskeletal and connective tissue disorders Joint swelling	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Musculoskeletal and connective tissue disorders Muscle spasms	12.5% 7/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Musculoskeletal and connective tissue disorders Muscular weakness	5.4% 3/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	12.5% 7/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Musculoskeletal and connective tissue disorders Musculoskeletal deformity	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	7.1% 4/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Musculoskeletal and connective tissue disorders Myalgia	8.9% 5/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Musculoskeletal and connective tissue disorders Neck pain	3.6% 2/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Musculoskeletal and connective tissue disorders Pain in extremity	10.7% 6/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Musculoskeletal and connective tissue disorders Pain in jaw	5.4% 3/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Musculoskeletal and connective tissue disorders Pathological fracture	3.6% 2/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Musculoskeletal and connective tissue disorders Pubic pain	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Musculoskeletal and connective tissue disorders Trigger finger	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bone neoplasm	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to spine	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Skin papilloma	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour pain	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Nervous system disorders Ageusia	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Nervous system disorders Ataxia	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Nervous system disorders Balance Disorder	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Nervous system disorders Convulsion	3.6% 2/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Nervous system disorders Disturbance in attention	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Nervous system disorders Dizziness	10.7% 6/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Nervous system disorders Dysgeusia	16.1% 9/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Nervous system disorders Head discomfort	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Nervous system disorders Headache	23.2% 13/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Nervous system disorders Hypoaesthesia	5.4% 3/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Nervous system disorders Hypogeusia	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Nervous system disorders Lethargy	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Nervous system disorders Lumbar radiculopathy	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Nervous system disorders Memory impairment	3.6% 2/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Nervous system disorders Peroneal nerve palsy	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Nervous system disorders Radiculopathy	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Nervous system disorders Restless legs syndrome	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Nervous system disorders Sinus headache	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Nervous system disorders Somnolence	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Nervous system disorders Spinal cord paralysis	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Nervous system disorders Peripheral Neuropathy	60.7% 34/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Nervous system disorders Neuropathy peripheral	46.4% 26/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Nervous system disorders Paraesthesia	7.1% 4/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Nervous system disorders Peripheral motor neuropathy	3.6% 2/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Nervous system disorders Peripheral sensory neuropathy	21.4% 12/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Psychiatric disorders Affect lability	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Psychiatric disorders Anxiety	5.4% 3/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Psychiatric disorders Depression	10.7% 6/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Psychiatric disorders Disorientation	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Psychiatric disorders Hallucination	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Psychiatric disorders Insomnia	14.3% 8/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Psychiatric disorders Mental status changes	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Renal and urinary disorders Dysuria	16.1% 9/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Renal and urinary disorders Hydronephrosis	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Renal and urinary disorders Micturition urgency	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Renal and urinary disorders Pollakiuria	7.1% 4/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Renal and urinary disorders Proteinuria	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Renal and urinary disorders Urinary incontinence	3.6% 2/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Renal and urinary disorders Urinary retention	3.6% 2/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Renal and urinary disorders Urinary tract obstruction	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Reproductive system and breast disorders Breast pain	5.4% 3/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Reproductive system and breast disorders Pelvic pain	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Reproductive system and breast disorders Vulvovaginal dryness	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Respiratory, thoracic and mediastinal disorders Cough	23.2% 13/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Respiratory, thoracic and mediastinal disorders Dry throat	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Respiratory, thoracic and mediastinal disorders Dysphonia	3.6% 2/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Respiratory, thoracic and mediastinal disorders Dyspnoea	12.5% 7/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	3.6% 2/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Respiratory, thoracic and mediastinal disorders Epistaxis	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Respiratory, thoracic and mediastinal disorders Hiccups	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Respiratory, thoracic and mediastinal disorders Nasal congestion	5.4% 3/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	5.4% 3/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Respiratory, thoracic and mediastinal disorders Paranasal sinus hypersecretion	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Respiratory, thoracic and mediastinal disorders Pleural effusion	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Respiratory, thoracic and mediastinal disorders Productive cough	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	5.4% 3/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Respiratory, thoracic and mediastinal disorders Respiratory tract congestion	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Respiratory, thoracic and mediastinal disorders Rhinitis allergic	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	5.4% 3/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Respiratory, thoracic and mediastinal disorders Throat irritation	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Respiratory, thoracic and mediastinal disorders Upper-airway cough syndrome	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Skin and subcutaneous tissue disorders Acne	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Skin and subcutaneous tissue disorders Alopecia	83.9% 47/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Skin and subcutaneous tissue disorders Dermatitis acneiform	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Skin and subcutaneous tissue disorders Dermatitis bullous	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Skin and subcutaneous tissue disorders Dry skin	5.4% 3/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Skin and subcutaneous tissue disorders Eczema	5.4% 3/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Skin and subcutaneous tissue disorders Hyperkeratosis	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Skin and subcutaneous tissue disorders Ingrown hair	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Skin and subcutaneous tissue disorders Nail discolouration	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Skin and subcutaneous tissue disorders Nail disorder	5.4% 3/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Skin and subcutaneous tissue disorders Night sweats	8.9% 5/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Skin and subcutaneous tissue disorders Onychoclasis	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Skin and subcutaneous tissue disorders Pruritus	5.4% 3/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Skin and subcutaneous tissue disorders Rash	7.1% 4/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Skin and subcutaneous tissue disorders Rash maculo-papular	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Skin and subcutaneous tissue disorders Rash pruritic	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Skin and subcutaneous tissue disorders Skin disorder	3.6% 2/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Skin and subcutaneous tissue disorders Skin irritation	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Vascular disorders Deep vein thrombosis	5.4% 3/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Vascular disorders Flushing	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Vascular disorders Hot flush	8.9% 5/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Vascular disorders Hypertension	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Vascular disorders Hypotension	3.6% 2/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Vascular disorders Lymphoedema	3.6% 2/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Vascular disorders Pallor	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Vascular disorders Phlebitis	3.6% 2/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Vascular disorders Thrombophlebitis superficial	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.
Nervous system disorders Dysarthria	1.8% 1/56 • All Treatment-Emergent Adverse events (TEAEs) were collected and followed from the time the participant signed the informed consent form (ICF) until 30 days after discontinuation of study drug or resolution. Participants were followed for up to 2.5 years. Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs rated as Grade 4 or 5 were considered serious.

Additional Information

Eisai Medical Services

Eisai Inc.

Phone: 1-888-422-4743

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place