Trial Outcomes & Findings for Safety and Efficacy Study of Enzalutamide Versus Bicalutamide in Men With Prostate Cancer (NCT NCT01664923)

NCT ID: NCT01664923

Last Updated: 2019-01-30

Results Overview

PFS was defined as time from randomization to earliest objective evidence of prostate specific-antigen (PSA) progression, radiographic progression, or death on study. PSA progression was defined as ≥ 25% increase in PSA with an absolute increase ≥ 2 ng/mL above the nadir and was to be confirmed by a second consecutive assessment. Radiographic progression in bone was based on The Prostate Cancer Clinical Trials Working Group (PCWG2) guidelines defined as at least 2 new lesions on bone scan. Radiographic progression in soft tissue on Computerized Tomography/Magnetic Resonance Imaging (CT/MRI) was based on Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). CT/MRI and bone scans were read locally by the same radiologist (or nuclear medicine physician for interpretation of bone scans) whenever possible. Participants not known to have had a PFS event at the time of the analysis data cutoff were censored at the date of last assessment.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 396 participants
• Primary outcome timeframe: From randomization until the data cut-off date of 09 February 2015, median duration of treatment was 14.7 months in the enzalutamide arm and 8.4 months in the bicalutamide arm.
• Results posted on: 2019-01-30

Participant Flow

Participant milestones

Measure	Enzalutamide Participants received enzalutamide 160 milligram (mg), self-administered as four 40-mg capsules, and 1 bicalutamide matching placebo capsule once per day, by mouth for up to 29 months in double blind (DB) phase. Participants who completed DB phase and consented to participate in open label phase, received enzalutamide 160 mg, self-administered as four 40-mg capsules once per day by mouth for up to 36 months in open label phase.	Bicalutamide Then Enzalutamide Participants received bicalutamide 50 mg, self-administered as 1 capsule, once per day by mouth and 4 enzalutamide matching placebo capsules for up to 29 months in DB phase. Participants who completed DB phase and consented to participate in open label phase, received enzalutamide 160 mg, self-administered as four 40-mg capsules, once per day by mouth for up to 36 months in open label phase.
Period1:Double Blind Phase-29 Months STARTED	198	198
Period1:Double Blind Phase-29 Months Received Study Treatment	197	198
Period1:Double Blind Phase-29 Months COMPLETED	93	38
Period1:Double Blind Phase-29 Months NOT COMPLETED	105	160
Period 2: Open-label Phase-36 Months STARTED	93	38
Period 2: Open-label Phase-36 Months Treated	93	37
Period 2: Open-label Phase-36 Months COMPLETED	52	15
Period 2: Open-label Phase-36 Months NOT COMPLETED	41	23

Reasons for withdrawal

Measure	Enzalutamide Participants received enzalutamide 160 milligram (mg), self-administered as four 40-mg capsules, and 1 bicalutamide matching placebo capsule once per day, by mouth for up to 29 months in double blind (DB) phase. Participants who completed DB phase and consented to participate in open label phase, received enzalutamide 160 mg, self-administered as four 40-mg capsules once per day by mouth for up to 36 months in open label phase.	Bicalutamide Then Enzalutamide Participants received bicalutamide 50 mg, self-administered as 1 capsule, once per day by mouth and 4 enzalutamide matching placebo capsules for up to 29 months in DB phase. Participants who completed DB phase and consented to participate in open label phase, received enzalutamide 160 mg, self-administered as four 40-mg capsules, once per day by mouth for up to 36 months in open label phase.
Period1:Double Blind Phase-29 Months Death	8	6
Period1:Double Blind Phase-29 Months Lost to Follow-up	0	1
Period1:Double Blind Phase-29 Months Protocol Violation	2	0
Period1:Double Blind Phase-29 Months Withdrawal by Subject	12	8
Period1:Double Blind Phase-29 Months Disease Progression	65	132
Period1:Double Blind Phase-29 Months Adverse Event	14	9
Period1:Double Blind Phase-29 Months Other	3	4
Period1:Double Blind Phase-29 Months Randomized, But Not treated	1	0
Period 2: Open-label Phase-36 Months Death	3	1
Period 2: Open-label Phase-36 Months On Treatment	1	1
Period 2: Open-label Phase-36 Months Disease progression	28	9
Period 2: Open-label Phase-36 Months Other	3	1
Period 2: Open-label Phase-36 Months Adverse Event	4	7
Period 2: Open-label Phase-36 Months Withdrawal by Subject	2	4

Baseline Characteristics

Safety and Efficacy Study of Enzalutamide Versus Bicalutamide in Men With Prostate Cancer

Baseline characteristics by cohort

Measure	Enzalutamide n=198 Participants Participants received enzalutamide 160 mg, self-administered as four 40-mg capsules, once per day by mouth and 1 bicalutamide-placebo capsule in DB phase.	Bicalutamide n=198 Participants Participants received bicalutamide 50 mg, self-administered as 1 capsule, once per day by mouth and 4 enzalutamide-placebo capsules in DB phase.	Total n=396 Participants Total of all reporting groups
Age, Customized < 65 years	39 Participants n=5 Participants	25 Participants n=7 Participants	64 Participants n=5 Participants
Age, Customized 65-74 years	82 Participants n=5 Participants	76 Participants n=7 Participants	158 Participants n=5 Participants
Age, Customized ≥ 75 years	77 Participants n=5 Participants	97 Participants n=7 Participants	174 Participants n=5 Participants
Sex/Gender, Customized Male	198 Participants n=5 Participants	198 Participants n=7 Participants	396 Participants n=5 Participants
Region of Enrollment United States	198 Participants n=5 Participants	198 Participants n=7 Participants	396 Participants n=5 Participants

PRIMARY outcome

Timeframe: From randomization until the data cut-off date of 09 February 2015, median duration of treatment was 14.7 months in the enzalutamide arm and 8.4 months in the bicalutamide arm.

Population: Intent-to-treat population: all participants randomly assigned to study treatment.

PFS was defined as time from randomization to earliest objective evidence of prostate specific-antigen (PSA) progression, radiographic progression, or death on study. PSA progression was defined as ≥ 25% increase in PSA with an absolute increase ≥ 2 ng/mL above the nadir and was to be confirmed by a second consecutive assessment. Radiographic progression in bone was based on The Prostate Cancer Clinical Trials Working Group (PCWG2) guidelines defined as at least 2 new lesions on bone scan. Radiographic progression in soft tissue on Computerized Tomography/Magnetic Resonance Imaging (CT/MRI) was based on Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). CT/MRI and bone scans were read locally by the same radiologist (or nuclear medicine physician for interpretation of bone scans) whenever possible. Participants not known to have had a PFS event at the time of the analysis data cutoff were censored at the date of last assessment.

Outcome measures

Measure	Enzalutamide n=198 Participants Participants received enzalutamide 160 mg, self-administered as four 40-mg capsules, once per day by mouth and 1 bicalutamide-placebo capsule in DB phase.	Bicalutamide n=198 Participants Participants received bicalutamide 50 mg, self-administered as 1 capsule, once per day by mouth and 4 enzalutamide-placebo capsules in DB phase.	Open Label Phase: Bicalutamide Crossover to Enzalutamide Participants who received bicalutamide 50 mg in DB phase and consented to participate in open label phase, received enzalutamide 160 mg, self-administered as four 40-mg capsules, once per day by mouth in open label phase for up to 36 months.
Progression Free Survival (PFS)	19.4 months Interval 16.5 to The upper limit of the 95% confidence interval was not available because an insufficient number of participants had an event at the time of analysis.	5.7 months Interval 5.6 to 8.1	—

SECONDARY outcome

Timeframe: From randomization until the data cut-off date of 09 February 2015, median duration of treatment was 14.7 months in the enzalutamide arm and 8.4 months in the bicalutamide arm.

Population: Intent-to-treat population: all participants randomly assigned to study treatment.

PSA progression was defined as ≥ 25% increase in PSA with an absolute increase ≥ 2 ng/mL above the nadir and was to be confirmed by a second consecutive assessment at least 3 weeks later. Participants not known to have had PSA progression were censored at the date of last PSA assessment.

Outcome measures

Measure	Enzalutamide n=198 Participants Participants received enzalutamide 160 mg, self-administered as four 40-mg capsules, once per day by mouth and 1 bicalutamide-placebo capsule in DB phase.	Bicalutamide n=198 Participants Participants received bicalutamide 50 mg, self-administered as 1 capsule, once per day by mouth and 4 enzalutamide-placebo capsules in DB phase.	Open Label Phase: Bicalutamide Crossover to Enzalutamide Participants who received bicalutamide 50 mg in DB phase and consented to participate in open label phase, received enzalutamide 160 mg, self-administered as four 40-mg capsules, once per day by mouth in open label phase for up to 36 months.
Time to PSA Progression	NA months Interval 19.4 to The median time to PSA progression and its upper limit of the 95% confidence interval were not available because an insufficient number of participants had an event at the time of analysis.	8.3 months Interval 5.7 to 8.5	—

SECONDARY outcome

Timeframe: From randomization until the data cut-off date of 09 February 2015, median duration of treatment was 14.7 months in the enzalutamide arm and 8.4 months in the bicalutamide arm.

Population: Evaluable intent-to-treat population: all participants randomly assigned to study treatment and had a baseline and at least 1 post baseline PSA measurement.

PSA response was defined as a reduction in PSA of at least 50% from baseline at any post baseline assessment confirmed by a second PSA assessment at least 3 weeks later.

Outcome measures

Measure	Enzalutamide n=192 Participants Participants received enzalutamide 160 mg, self-administered as four 40-mg capsules, once per day by mouth and 1 bicalutamide-placebo capsule in DB phase.	Bicalutamide n=195 Participants Participants received bicalutamide 50 mg, self-administered as 1 capsule, once per day by mouth and 4 enzalutamide-placebo capsules in DB phase.	Open Label Phase: Bicalutamide Crossover to Enzalutamide Participants who received bicalutamide 50 mg in DB phase and consented to participate in open label phase, received enzalutamide 160 mg, self-administered as four 40-mg capsules, once per day by mouth in open label phase for up to 36 months.
Percentage of Participants With a PSA Response ≥ 50%	81.3 percentage of participants Interval 75.0 to 86.5	31.3 percentage of participants Interval 24.8 to 38.3	—

SECONDARY outcome

Timeframe: From randomization until the data cut-off date of 09 February 2015, median duration of treatment was 14.7 months in the enzalutamide arm and 8.4 months in the bicalutamide arm.

Population: All participants with metastatic disease at study entry and randomly assigned to study treatment.

Duration of radiographic PFS was defined as the time from randomization to the earliest objective evidence of radiographic disease progression or death on study and was to be evaluated for participants with metastatic disease at study entry. Radiographic disease progression in bone was based on PCWG2 guidelines defined as at least 2 new lesions on bone scan. Radiographic disease progression in soft tissue on CT/MRI was based on RECIST 1.1. CT/MRI and bone scans were read locally by the same radiologist (or nuclear medicine physician for interpretation of bone scans) whenever possible. Participants not known to have had radiographic progression at the time of analysis data cutoff were censored at the date of last radiographic assessment.

Outcome measures

Measure	Enzalutamide n=128 Participants Participants received enzalutamide 160 mg, self-administered as four 40-mg capsules, once per day by mouth and 1 bicalutamide-placebo capsule in DB phase.	Bicalutamide n=129 Participants Participants received bicalutamide 50 mg, self-administered as 1 capsule, once per day by mouth and 4 enzalutamide-placebo capsules in DB phase.	Open Label Phase: Bicalutamide Crossover to Enzalutamide Participants who received bicalutamide 50 mg in DB phase and consented to participate in open label phase, received enzalutamide 160 mg, self-administered as four 40-mg capsules, once per day by mouth in open label phase for up to 36 months.
Duration of Radiographic PFS	NA months Interval 16.7 to The median duration of radiographic PFS and its upper limit of the 95% confidence interval were not available because an insufficient number of participants had an event at the time of analysis.	8.3 months Interval 8.1 to 11.1	—

SECONDARY outcome

Timeframe: From randomization until the data cut-off date of 09 February 2015, median duration of treatment was 14.7 months in the enzalutamide arm and 8.4 months in the bicalutamide arm.

Population: Intent-to-treat population: all participants randomly assigned to study treatment.

The FACT-P is a multidimensional, self-reported quality of life instrument consisting of 27 core items that assess patient function in 4 domains: physical, social/family, emotional, and functional well-being, and supplemented by 12 site-specific items to assess for prostate-related symptoms. Each item is rated on a 0 to 4 Likert-type scale, and then combined to produce subscale scores for each domain, as well as a global quality of life score (0 to 156) with higher scores representing better quality of life. Time to degradation of FACT-P was defined as the time from randomization to first assessment with at least a 10-point decrease from baseline in the global FACT-P score for each participant. Participants with no score degradation at the time of analysis data cutoff were censored at the date of last assessment showing no degradation.

Outcome measures

Measure	Enzalutamide n=198 Participants Participants received enzalutamide 160 mg, self-administered as four 40-mg capsules, once per day by mouth and 1 bicalutamide-placebo capsule in DB phase.	Bicalutamide n=198 Participants Participants received bicalutamide 50 mg, self-administered as 1 capsule, once per day by mouth and 4 enzalutamide-placebo capsules in DB phase.	Open Label Phase: Bicalutamide Crossover to Enzalutamide Participants who received bicalutamide 50 mg in DB phase and consented to participate in open label phase, received enzalutamide 160 mg, self-administered as four 40-mg capsules, once per day by mouth in open label phase for up to 36 months.
Quality of Life: Time to Degradation of Functional Assessment of Cancer Therapy - Prostate (FACT-P)	8.4 months Interval 6.3 to 11.4	8.3 months Interval 6.1 to 11.1	—

SECONDARY outcome

Timeframe: From randomization until the data cut-off date of 09 February 2015, median duration of treatment was 14.7 months in the enzalutamide arm and 8.4 months in the bicalutamide arm.

Population: All participants who were randomly assigned to study treatment and had metastatic and measurable soft tissue disease at screening.

Best overall soft tissue response is defined as partial response (PR) or complete response (CR) while on study treatment based on investigator assessment of target, nontarget, and new lesions using RECIST 1.1. Only participants in the metastatic population with measurable soft tissue disease (at least 1 target lesion identified per RECIST 1.1) at screening were included in the analysis. All percentages are based on number of participants with metastatic and measurable soft tissue disease at screening in each treatment group.

Outcome measures

Measure	Enzalutamide n=35 Participants Participants received enzalutamide 160 mg, self-administered as four 40-mg capsules, once per day by mouth and 1 bicalutamide-placebo capsule in DB phase.	Bicalutamide n=43 Participants Participants received bicalutamide 50 mg, self-administered as 1 capsule, once per day by mouth and 4 enzalutamide-placebo capsules in DB phase.	Open Label Phase: Bicalutamide Crossover to Enzalutamide Participants who received bicalutamide 50 mg in DB phase and consented to participate in open label phase, received enzalutamide 160 mg, self-administered as four 40-mg capsules, once per day by mouth in open label phase for up to 36 months.
Best Overall Soft Tissue Response	60.0 percentage of participants Interval 42.11 to 76.13	14.0 percentage of participants Interval 5.3 to 27.93	—

SECONDARY outcome

Timeframe: From first dose of study drug until the end of open label phase (up to maximum duration of 65 months)

Population: Safety population included all participants who received at least 1 dose of study drug.

An AE was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. An SAE was an AE resulting in any of following outcomes or deemed significant for any other reason: death, initial or prolonged inpatient hospitalization, life-threatening experience (immediate risk of dying), persistent or significant disability or incapacity, congenital anomaly. A treatment emergent AE defined as an event that emerged during treatment period (From first dose of study drug until end of open label phase [up to maximum duration of 65 months]) that was absent before treatment, or worsened during treatment period relative to pre-treatment state. AE included both serious and non- SAE. Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. An AE was considered related to study drug if event was assessed by investigator as probably or possibly related.

Outcome measures

Measure	Enzalutamide n=197 Participants Participants received enzalutamide 160 mg, self-administered as four 40-mg capsules, once per day by mouth and 1 bicalutamide-placebo capsule in DB phase.	Bicalutamide n=198 Participants Participants received bicalutamide 50 mg, self-administered as 1 capsule, once per day by mouth and 4 enzalutamide-placebo capsules in DB phase.	Open Label Phase: Bicalutamide Crossover to Enzalutamide n=37 Participants Participants who received bicalutamide 50 mg in DB phase and consented to participate in open label phase, received enzalutamide 160 mg, self-administered as four 40-mg capsules, once per day by mouth in open label phase for up to 36 months.
Percentage of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) Any AE	96.4 percentage of participants	90.4 percentage of participants	97.3 percentage of participants
Percentage of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) AE Leading to Study Drug Discontinuation	16.2 percentage of participants	13.1 percentage of participants	24.3 percentage of participants
Percentage of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) AE Leading to Death	4.6 percentage of participants	3.0 percentage of participants	8.1 percentage of participants
Percentage of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) Serious AE	38.6 percentage of participants	30.3 percentage of participants	43.2 percentage of participants
Percentage of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) AE Related to Study Drug	66.5 percentage of participants	53.5 percentage of participants	70.3 percentage of participants
Percentage of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) Serious AE Related to Study Drug	7.6 percentage of participants	3.5 percentage of participants	2.7 percentage of participants

Adverse Events

Enzalutamide

Serious events: 76 serious events

Other events: 187 other events

Deaths: 0 deaths

DB Phase: Bicalutamide

Serious events: 60 serious events

Other events: 179 other events

Deaths: 0 deaths

Open Label Phase: Bicalutamide Crossover to Enzalutamide

Serious events: 16 serious events

Other events: 36 other events

Deaths: 0 deaths

Serious adverse events

Measure	Enzalutamide n=197 participants at risk Participants received enzalutamide 160 mg, self-administered as four 40-mg capsules, once per day by mouth and 1 bicalutamide-placebo capsule for up to 29 months in DB phase. Participants who completed DB phase and consented to participate in open label phase, received same treatment for up to 36 months in open label phase.	DB Phase: Bicalutamide n=198 participants at risk Participants received bicalutamide 50 mg, self-administered as 1 capsule, once per day by mouth and 4 enzalutamide-placebo capsules for up to 29 months in DB phase.	Open Label Phase: Bicalutamide Crossover to Enzalutamide n=37 participants at risk Participants who received bicalutamide 50 mg in DB phase and consented to participate in open label phase, received enzalutamide 160 mg, self-administered as four 40-mg capsules, once per day by mouth in open label phase for up to 36 months.
Injury, poisoning and procedural complications Head injury	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Injury, poisoning and procedural complications Hip fracture	1.0% 2/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Injury, poisoning and procedural complications Injury	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	1.0% 2/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Injury, poisoning and procedural complications Overdose	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Injury, poisoning and procedural complications Pubis fracture	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Injury, poisoning and procedural complications Rib fracture	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Injury, poisoning and procedural complications Spinal compression fracture	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Nervous system disorders Hypoglycaemic encephalopathy	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Investigations Alanine aminotransferase increased	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Investigations Aspartate aminotransferase increased	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Investigations Liver function test abnormal	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Metabolism and nutrition disorders Decreased appetite	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Metabolism and nutrition disorders Dehydration	1.0% 2/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Metabolism and nutrition disorders Diabetic ketoacidosis	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Metabolism and nutrition disorders Gout	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Metabolism and nutrition disorders Hypercalcaemia	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Metabolism and nutrition disorders Hyperglycaemia	1.0% 2/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Metabolism and nutrition disorders Hypovolaemia	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Metabolism and nutrition disorders Malnutrition	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Musculoskeletal and connective tissue disorders Arthralgia	1.0% 2/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Musculoskeletal and connective tissue disorders Back pain	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Musculoskeletal and connective tissue disorders Intervertebral disc displacement	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Musculoskeletal and connective tissue disorders Lumbar spinal stenosis	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Nervous system disorders Metabolic encephalopathy	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Musculoskeletal and connective tissue disorders Muscular weakness	1.0% 2/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Musculoskeletal and connective tissue disorders Musculoskeletal pain	1.0% 2/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Musculoskeletal and connective tissue disorders Osteoarthritis	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Musculoskeletal and connective tissue disorders Pathological fracture	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	1.0% 2/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma of colon	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Nervous system disorders Presyncope	1.0% 2/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder transitional cell carcinoma	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cancer pain	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer metastatic	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Nervous system disorders Syncope	1.5% 3/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	1.0% 2/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Erythroleukaemia	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Nervous system disorders Transient ischaemic attack	2.5% 5/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Intraductal papillary mucinous neoplasm	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to adrenals	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to liver	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to spine	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Psychiatric disorders Delirium	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastatic pain	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Myelofibrosis	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pancreatic carcinoma	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer metastatic	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal cell carcinoma	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Psychiatric disorders Mental status changes	1.0% 2/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of lung	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of skin	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Transitional cell carcinoma	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour necrosis	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Nervous system disorders Amnesia	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Nervous system disorders Carotid artery stenosis	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Nervous system disorders Cerebrovascular accident	1.0% 2/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Nervous system disorders Cervical cord compression	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Nervous system disorders Convulsion	1.0% 2/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Nervous system disorders Dizziness	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Nervous system disorders Encephalopathy	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Nervous system disorders Headache	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Nervous system disorders Hemiparesis	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Blood and lymphatic system disorders Anaemia	2.0% 4/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.0% 4/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	5.4% 2/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Blood and lymphatic system disorders Lymphadenitis	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Cardiac disorders Acute coronary syndrome	1.0% 2/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Cardiac disorders Acute myocardial infarction	1.0% 2/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Cardiac disorders Cardio-respiratory arrest	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Cardiac disorders Angina pectoris	2.5% 5/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Cardiac disorders Aortic valve disease	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Cardiac disorders Atrial fibrillation	1.0% 2/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Cardiac disorders Atrial flutter	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Cardiac disorders Atrioventricular block	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Cardiac disorders Bradycardia	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Cardiac disorders Cardiac failure	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Cardiac disorders Cardiac failure congestive	2.5% 5/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	1.0% 2/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	5.4% 2/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Cardiac disorders Coronary artery disease	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Cardiac disorders Palpitations	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Cardiac disorders Stress cardiomyopathy	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Cardiac disorders Supraventricular tachycardia	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Cardiac disorders Ventricular tachycardia	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Ear and labyrinth disorders Vertigo	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Endocrine disorders Inappropriate antidiuretic hormone secretion	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Gastrointestinal disorders Abdominal pain	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Gastrointestinal disorders Constipation	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Gastrointestinal disorders Diarrhoea	1.0% 2/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Gastrointestinal disorders Diverticulum intestinal haemorrhagic	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Gastrointestinal disorders Duodenal ulcer	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Gastrointestinal disorders Dysphagia	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Gastrointestinal disorders Gastric haemorrhage	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Gastrointestinal disorders Gastric ulcer	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Gastrointestinal disorders Gastrointestinal haemorrhage	1.0% 2/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Gastrointestinal disorders Ileus	1.0% 2/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Gastrointestinal disorders Large intestinal stenosis	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Gastrointestinal disorders Odynophagia	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Gastrointestinal disorders Rectal haemorrhage	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Gastrointestinal disorders Small intestinal obstruction	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Gastrointestinal disorders Upper gastrointestinal haemorrhage	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
General disorders Asthenia	2.5% 5/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
General disorders Chest pain	1.0% 2/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
General disorders Device occlusion	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
General disorders Fatigue	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	1.0% 2/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
General disorders General physical health deterioration	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
General disorders Non-cardiac chest pain	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
General disorders Pyrexia	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Hepatobiliary disorders Cholecystitis acute	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Hepatobiliary disorders Cholecystitis chronic	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Hepatobiliary disorders Hepatic failure	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Infections and infestations Bronchitis	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Infections and infestations Cellulitis	1.5% 3/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Infections and infestations Hepatitis B	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Infections and infestations Lobar pneumonia	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Infections and infestations Peritonitis	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Infections and infestations Pneumonia	3.0% 6/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.0% 4/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Infections and infestations Pulmonary sepsis	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Infections and infestations Pyelonephritis	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	1.0% 2/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Infections and infestations Pyelonephritis acute	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Infections and infestations Sepsis	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	1.5% 3/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Infections and infestations Septic shock	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	1.0% 2/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Infections and infestations Skin infection	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Infections and infestations Subcutaneous abscess	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Infections and infestations Urinary tract infection	1.0% 2/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	3.0% 6/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Infections and infestations Urosepsis	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	1.5% 3/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Injury, poisoning and procedural complications Fall	2.5% 5/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Psychiatric disorders Suicide attempt	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Renal and urinary disorders Bladder obstruction	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Renal and urinary disorders Bladder outlet obstruction	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Renal and urinary disorders Calculus bladder	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Renal and urinary disorders Dysuria	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Renal and urinary disorders Haematuria	2.5% 5/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.0% 4/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Renal and urinary disorders Hydronephrosis	2.0% 4/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Renal and urinary disorders Nephrolithiasis	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Renal and urinary disorders Postrenal failure	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Renal and urinary disorders Renal failure	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Renal and urinary disorders Renal failure acute	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Renal and urinary disorders Urinary retention	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	1.0% 2/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Renal and urinary disorders Urinary tract obstruction	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Renal and urinary disorders Vesical fistula	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Reproductive system and breast disorders Prostatic calcification	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Respiratory, thoracic and mediastinal disorders Asthma	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	1.0% 2/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	1.5% 3/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Skin and subcutaneous tissue disorders Dermatitis psoriasiform	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Skin and subcutaneous tissue disorders Rash maculo-papular	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Vascular disorders Accelerated hypertension	1.0% 2/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Vascular disorders Aortic stenosis	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Vascular disorders Deep vein thrombosis	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	1.5% 3/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Vascular disorders Hypertension	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Vascular disorders Hypotension	1.0% 2/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Vascular disorders Peripheral artery thrombosis	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Cardiac disorders Myocardial infarction	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Cardiac disorders Ventricular fibrillation	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Cardiac disorders Arrhythmia	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Cardiac disorders Atrioventricular block complete	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Gastrointestinal disorders Duodenal perforation	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Gastrointestinal disorders Lower gastrointestinal haemorrhage	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Gastrointestinal disorders Ascites	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Gastrointestinal disorders Duodenal ulcer perforation	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
General disorders Disease progression	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Infections and infestations Appendicitis perforated	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Infections and infestations Cystitis	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Infections and infestations Urinary bladder abscess	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Infections and infestations Appendicitis	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Infections and infestations Wound infection	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Infections and infestations Device related infection	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Infections and infestations Osteomyelitis	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Infections and infestations Postoperative wound infection	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Injury, poisoning and procedural complications Subdural haematoma	1.0% 2/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Injury, poisoning and procedural complications Craniocerebral injury	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Injury, poisoning and procedural complications Femoral neck fracture	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Injury, poisoning and procedural complications Urinary bladder rupture	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Injury, poisoning and procedural complications Alcohol poisoning	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Injury, poisoning and procedural complications Cystitis radiation	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	5.4% 2/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Investigations Troponin increased	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Injury, poisoning and procedural complications Radius fracture	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Injury, poisoning and procedural complications Ulna fracture	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Investigations International normalised ratio increased	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Musculoskeletal and connective tissue disorders Spinal column stenosis	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Musculoskeletal and connective tissue disorders Spondylolisthesis	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder cancer	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cholangiocarcinoma	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Nervous system disorders Dyskinesia	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Small cell lung cancer	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant melanoma	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Nervous system disorders Cognitive disorder	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Nervous system disorders Subarachnoid haemorrhage	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Nervous system disorders Haemorrhage intracranial	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Nervous system disorders Haemorrhagic stroke	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	5.4% 2/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Nervous system disorders Hydrocephalus	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Renal and urinary disorders Cystitis haemorrhagic	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Renal and urinary disorders Obstructive uropathy	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Renal and urinary disorders Urethral stenosis	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Skin and subcutaneous tissue disorders Skin ulcer	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Surgical and medical procedures Umbilical hernia repair	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Vascular disorders Orthostatic hypotension	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Injury, poisoning and procedural complications Femur fracture	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study

Other adverse events

Measure	Enzalutamide n=197 participants at risk Participants received enzalutamide 160 mg, self-administered as four 40-mg capsules, once per day by mouth and 1 bicalutamide-placebo capsule for up to 29 months in DB phase. Participants who completed DB phase and consented to participate in open label phase, received same treatment for up to 36 months in open label phase.	DB Phase: Bicalutamide n=198 participants at risk Participants received bicalutamide 50 mg, self-administered as 1 capsule, once per day by mouth and 4 enzalutamide-placebo capsules for up to 29 months in DB phase.	Open Label Phase: Bicalutamide Crossover to Enzalutamide n=37 participants at risk Participants who received bicalutamide 50 mg in DB phase and consented to participate in open label phase, received enzalutamide 160 mg, self-administered as four 40-mg capsules, once per day by mouth in open label phase for up to 36 months.
Infections and infestations Respiratory tract infection	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Gastrointestinal disorders Abdominal pain	7.6% 15/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	3.0% 6/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Gastrointestinal disorders Constipation	14.7% 29/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	16.7% 33/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	16.2% 6/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Gastrointestinal disorders Diarrhoea	13.2% 26/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	14.6% 29/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	24.3% 9/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Gastrointestinal disorders Nausea	19.3% 38/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	16.2% 32/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	24.3% 9/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Gastrointestinal disorders Vomiting	6.1% 12/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	8.6% 17/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	8.1% 3/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
General disorders Asthenia	8.1% 16/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.5% 5/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	5.4% 2/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
General disorders Fatigue	41.6% 82/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	28.3% 56/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	27.0% 10/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
General disorders Pyrexia	2.5% 5/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	6.1% 12/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Musculoskeletal and connective tissue disorders Arthralgia	22.8% 45/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	14.6% 29/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	13.5% 5/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Musculoskeletal and connective tissue disorders Back pain	20.8% 41/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	17.2% 34/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	8.1% 3/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Musculoskeletal and connective tissue disorders Muscular weakness	6.6% 13/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	3.0% 6/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Musculoskeletal and connective tissue disorders Musculoskeletal pain	8.1% 16/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	5.6% 11/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	5.4% 2/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Musculoskeletal and connective tissue disorders Pain in extremity	11.7% 23/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	5.1% 10/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Nervous system disorders Dizziness	13.2% 26/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	7.6% 15/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	16.2% 6/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Nervous system disorders Headache	7.1% 14/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	7.6% 15/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Psychiatric disorders Anxiety	6.6% 13/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	1.5% 3/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Psychiatric disorders Depression	7.6% 15/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	4.0% 8/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	5.4% 2/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Psychiatric disorders Insomnia	11.2% 22/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	4.5% 9/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	5.4% 2/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Renal and urinary disorders Haematuria	8.1% 16/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	6.6% 13/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	8.1% 3/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Renal and urinary disorders Renal failure acute	3.6% 7/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	6.1% 12/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Respiratory, thoracic and mediastinal disorders Dyspnoea	9.6% 19/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	6.1% 12/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Skin and subcutaneous tissue disorders Rash	6.1% 12/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	4.5% 9/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	8.1% 3/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Vascular disorders Hot flush	17.3% 34/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	10.1% 20/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	5.4% 2/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Vascular disorders Hypertension	12.7% 25/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	5.1% 10/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	13.5% 5/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Blood and lymphatic system disorders Haemorrhagic anaemia	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Blood and lymphatic system disorders Increased tendency to bruise	1.0% 2/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Blood and lymphatic system disorders Iron deficiency anaemia	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Blood and lymphatic system disorders Leukocytosis	1.0% 2/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Blood and lymphatic system disorders Anaemia	11.2% 22/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	10.6% 21/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	8.1% 3/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Blood and lymphatic system disorders Lymphadenitis	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Blood and lymphatic system disorders Lymphadenopathy	1.0% 2/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Blood and lymphatic system disorders Neutropenia	1.5% 3/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Blood and lymphatic system disorders Pancytopenia	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Blood and lymphatic system disorders Thrombocytopenia	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	1.5% 3/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Congenital, familial and genetic disorders Branchial cyst	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Congenital, familial and genetic disorders Phimosis	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Congenital, familial and genetic disorders Type V hyperlipidaemia	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Ear and labyrinth disorders Cerumen impaction	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Ear and labyrinth disorders Deafness	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Ear and labyrinth disorders Deafness bilateral	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Ear and labyrinth disorders Ear discomfort	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Ear and labyrinth disorders Ear haemorrhage	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Ear and labyrinth disorders Ear pain	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Ear and labyrinth disorders Hearing impaired	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Ear and labyrinth disorders Otorrhoea	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Ear and labyrinth disorders Tinnitus	1.0% 2/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Ear and labyrinth disorders Vertigo	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Ear and labyrinth disorders Vertigo positional	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Ear and labyrinth disorders Vestibular disorder	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Endocrine disorders Hyperparathyroidism	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Endocrine disorders Hypothyroidism	2.5% 5/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Endocrine disorders Inappropriate antidiuretic hormone secretion	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Endocrine disorders Thyroid cyst	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Hepatobiliary disorders Cholangitis	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Hepatobiliary disorders Cholelithiasis	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Hepatobiliary disorders Gallbladder disorder	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Hepatobiliary disorders Hepatic cirrhosis	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	1.0% 2/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Hepatobiliary disorders Hyperbilirubinaemia	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Hepatobiliary disorders Liver injury	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Immune system disorders Drug hypersensitivity	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Immune system disorders Seasonal allergy	1.0% 2/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Benign salivary gland neoplasm	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder neoplasm	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cancer pain	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon adenoma	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Gastrointestinal disorders Abdominal adhesions	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Gastrointestinal disorders Abdominal discomfort	2.0% 4/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	1.0% 2/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Gastrointestinal disorders Abdominal distension	2.0% 4/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	1.5% 3/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Gastrointestinal disorders Abdominal hernia	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Gastrointestinal disorders Abdominal pain lower	1.5% 3/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	1.5% 3/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Gastrointestinal disorders Abdominal pain upper	1.5% 3/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	1.0% 2/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Gastrointestinal disorders Abdominal tenderness	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Gastrointestinal disorders Acquired oesophageal web	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Gastrointestinal disorders Anal fissure	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Gastrointestinal disorders Ascites	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Gastrointestinal disorders Bowel movement irregularity	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Gastrointestinal disorders Colitis	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Gastrointestinal disorders Colitis ulcerative	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Gastrointestinal disorders Defaecation urgency	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Gastrointestinal disorders Diverticulum	1.5% 3/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	1.0% 2/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Gastrointestinal disorders Dry mouth	1.5% 3/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	1.0% 2/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Gastrointestinal disorders Duodenal ulcer	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Gastrointestinal disorders Duodenitis	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Gastrointestinal disorders Dyspepsia	3.0% 6/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.5% 5/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Gastrointestinal disorders Dysphagia	2.0% 4/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.0% 4/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Gastrointestinal disorders Erosive oesophagitis	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Gastrointestinal disorders Faecal incontinence	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Gastrointestinal disorders Faeces discoloured	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Gastrointestinal disorders Flatulence	4.6% 9/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.5% 5/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Gastrointestinal disorders Frequent bowel movements	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Gastrointestinal disorders Gastric haemorrhage	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Gastrointestinal disorders Gastric ulcer	2.0% 4/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Gastrointestinal disorders Gastritis	4.1% 8/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	1.0% 2/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Gastrointestinal disorders Gastritis haemorrhagic	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Gastrointestinal disorders Gastrointestinal angiodysplasia	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Gastrointestinal disorders Gastrointestinal disorder	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Gastrointestinal disorders Gastrointestinal haemorrhage	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Gastrointestinal disorders Gastrointestinal pain	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Gastrointestinal disorders Gastrooesophageal reflux disease	5.1% 10/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	1.0% 2/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	16.2% 6/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Gastrointestinal disorders Gingival swelling	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Gastrointestinal disorders Haematochezia	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Gastrointestinal disorders Haemorrhoids	1.0% 2/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	1.0% 2/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Gastrointestinal disorders Hiatus hernia	1.0% 2/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	1.0% 2/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Gastrointestinal disorders Ileus	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Gastrointestinal disorders Impaired gastric emptying	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Gastrointestinal disorders Large intestine polyp	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	1.0% 2/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Gastrointestinal disorders Mesenteric artery stenosis	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Gastrointestinal disorders Mouth haemorrhage	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Gastrointestinal disorders Oesophageal achalasia	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Gastrointestinal disorders Oesophageal dilatation	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Gastrointestinal disorders Oesophageal disorder	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Gastrointestinal disorders Oesophageal stenosis	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	1.0% 2/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Gastrointestinal disorders Oesophagitis	1.5% 3/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Gastrointestinal disorders Pancreatic atrophy	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Gastrointestinal disorders Pancreatic cyst	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Gastrointestinal disorders Rectal discharge	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Gastrointestinal disorders Rectal haemorrhage	1.5% 3/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Gastrointestinal disorders Rectal tenesmus	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Gastrointestinal disorders Retching	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Gastrointestinal disorders Salivary hypersecretion	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Gastrointestinal disorders Stomatitis	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Gastrointestinal disorders Tongue discolouration	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Gastrointestinal disorders Tongue ulceration	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Gastrointestinal disorders Tooth loss	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Gastrointestinal disorders Toothache	1.5% 3/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	1.0% 2/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Gastrointestinal disorders Umbilical hernia	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
General disorders Chest discomfort	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
General disorders Chest pain	3.0% 6/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	1.0% 2/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
General disorders Chills	2.5% 5/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	1.0% 2/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
General disorders Device dislocation	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
General disorders Device occlusion	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
General disorders Discomfort	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
General disorders Early satiety	1.5% 3/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
General disorders Face oedema	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
General disorders Gait disturbance	3.0% 6/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
General disorders Generalised oedema	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	1.5% 3/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
General disorders Inflammation	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
General disorders Influenza like illness	2.5% 5/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.5% 5/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
General disorders Injection site reaction	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
General disorders Local swelling	2.0% 4/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
General disorders Localised oedema	1.0% 2/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
General disorders Malaise	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	1.0% 2/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
General disorders Mucosal inflammation	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
General disorders Oedema	1.0% 2/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
General disorders Oedema peripheral	8.6% 17/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	5.1% 10/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
General disorders Pain	3.6% 7/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.5% 5/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
General disorders Suprapubic pain	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
General disorders Temperature intolerance	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
General disorders Thirst	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Infections and infestations Abscess limb	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Infections and infestations Abscess soft tissue	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Infections and infestations Acute sinusitis	1.0% 2/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Infections and infestations Appendicitis	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Infections and infestations Asymptomatic bacteriuria	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Infections and infestations Axillary candidiasis	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Infections and infestations Bacteraemia	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Infections and infestations Bacterial disease carrier	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Infections and infestations Bacteriuria	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Infections and infestations Bronchitis	3.6% 7/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Infections and infestations Candida infection	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Infections and infestations Cellulitis	2.5% 5/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Infections and infestations Chronic sinusitis	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Infections and infestations Cystitis	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Infections and infestations Diverticulitis	1.5% 3/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Infections and infestations Ear infection	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	1.0% 2/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Infections and infestations Fungal infection	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Infections and infestations Furuncle	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Infections and infestations Gastroenteritis viral	1.0% 2/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Infections and infestations Genital infection fungal	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Infections and infestations Gingival infection	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Infections and infestations Gingivitis	1.0% 2/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Infections and infestations Helicobacter infection	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Infections and infestations Hepatitis B	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
General disorders Non-cardiac chest pain	1.0% 2/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.5% 5/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Infections and infestations Herpes zoster	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Infections and infestations Hordeolum	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Infections and infestations Incision site infection	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Infections and infestations Infected cyst	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Infections and infestations Influenza	2.5% 5/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Infections and infestations Kidney infection	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Infections and infestations Klebsiella bacteraemia	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Infections and infestations Lobar pneumonia	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Infections and infestations Mucosal infection	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Infections and infestations Nasopharyngitis	4.1% 8/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	5.6% 11/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Infections and infestations Onychomycosis	1.0% 2/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Infections and infestations Oral candidiasis	1.0% 2/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Infections and infestations Oral herpes	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Infections and infestations Oropharyngitis fungal	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Infections and infestations Otitis externa	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Infections and infestations Otitis media	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Infections and infestations Peripheral nerve infection	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Infections and infestations Peritonitis	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Infections and infestations Pharyngitis	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Infections and infestations Pneumonia	2.5% 5/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	3.0% 6/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Infections and infestations Postoperative wound infection	1.0% 2/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Infections and infestations Rhinitis	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Infections and infestations Sinusitis	3.0% 6/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.5% 5/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Infections and infestations Skin infection	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Infections and infestations Tinea infection	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Infections and infestations Tinea pedis	2.0% 4/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Infections and infestations Tooth abscess	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Infections and infestations Tooth infection	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	1.0% 2/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Infections and infestations Upper respiratory tract infection	4.1% 8/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	4.0% 8/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Infections and infestations Urinary bladder abscess	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Infections and infestations Urinary tract infection	7.1% 14/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	10.6% 21/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	18.9% 7/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Infections and infestations Viral upper respiratory tract infection	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Infections and infestations Wound infection	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Infections and infestations Wound infection staphylococcal	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Injury, poisoning and procedural complications Alcohol poisoning	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Injury, poisoning and procedural complications Ankle fracture	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Injury, poisoning and procedural complications Clavicle fracture	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Injury, poisoning and procedural complications Compression fracture	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Injury, poisoning and procedural complications Contrast media reaction	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Injury, poisoning and procedural complications Contusion	2.5% 5/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Injury, poisoning and procedural complications Cystitis radiation	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Injury, poisoning and procedural complications Eschar	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Injury, poisoning and procedural complications Excoriation	1.5% 3/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Injury, poisoning and procedural complications Facial bones fracture	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	1.0% 2/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Injury, poisoning and procedural complications Fall	19.8% 39/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	9.6% 19/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	21.6% 8/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Injury, poisoning and procedural complications Femoral neck fracture	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Injury, poisoning and procedural complications Fibula fracture	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Injury, poisoning and procedural complications Foot fracture	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Injury, poisoning and procedural complications Fracture	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Injury, poisoning and procedural complications Fractured coccyx	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Injury, poisoning and procedural complications Hand fracture	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Injury, poisoning and procedural complications Head injury	1.0% 2/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Injury, poisoning and procedural complications Humerus fracture	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Injury, poisoning and procedural complications Incision site pain	1.0% 2/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Injury, poisoning and procedural complications Joint injury	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	1.0% 2/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Injury, poisoning and procedural complications Laceration	5.1% 10/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	1.5% 3/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Injury, poisoning and procedural complications Limb injury	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Injury, poisoning and procedural complications Lumbar vertebral fracture	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Injury, poisoning and procedural complications Meniscus injury	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Injury, poisoning and procedural complications Muscle strain	1.0% 2/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Injury, poisoning and procedural complications Procedural pain	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.0% 4/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	5.4% 2/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Injury, poisoning and procedural complications Radiation injury	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Injury, poisoning and procedural complications Radiation pneumonitis	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Injury, poisoning and procedural complications Radius fracture	2.0% 4/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Injury, poisoning and procedural complications Rib fracture	3.6% 7/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	3.0% 6/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Injury, poisoning and procedural complications Skeletal injury	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Injury, poisoning and procedural complications Spinal column injury	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Injury, poisoning and procedural complications Spinal compression fracture	2.0% 4/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Injury, poisoning and procedural complications Splinter	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Injury, poisoning and procedural complications Stress fracture	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Injury, poisoning and procedural complications Thoracic vertebral fracture	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Injury, poisoning and procedural complications Vth nerve injury	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Injury, poisoning and procedural complications Wound	1.0% 2/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Investigations Alanine aminotransferase increased	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	1.5% 3/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Investigations Aspartate aminotransferase increased	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.5% 5/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Investigations Blood albumin decreased	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Investigations Blood alkaline phosphatase increased	2.5% 5/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	5.6% 11/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Investigations Blood bicarbonate decreased	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Investigations Blood bilirubin increased	1.5% 3/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Investigations Blood calcium increased	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Investigations Blood cholesterol increased	1.0% 2/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	1.0% 2/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Investigations Blood creatine phosphokinase increased	3.0% 6/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	3.5% 7/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Investigations Blood creatinine increased	2.5% 5/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	3.5% 7/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Investigations Blood glucose increased	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	1.5% 3/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Investigations Blood lactate dehydrogenase increased	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.0% 4/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Investigations Blood lactic acid increased	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Investigations Blood parathyroid hormone increased	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Investigations Blood potassium increased	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Investigations Blood pressure increased	1.5% 3/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	5.4% 2/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Investigations Blood sodium decreased	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Investigations Blood urine present	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Investigations Cardiac murmur	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Investigations Face and mouth X-ray abnormal	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Investigations Haemoglobin decreased	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.0% 4/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Investigations Helicobacter test positive	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Investigations International normalised ratio fluctuation	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Investigations International normalised ratio increased	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	1.0% 2/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Investigations Intraocular pressure increased	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Investigations Low density lipoprotein increased	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Investigations Lymphocyte count decreased	1.0% 2/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Investigations Lymphocyte count increased	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Investigations Neutrophil count decreased	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Investigations Neutrophil count increased	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Investigations Occult blood positive	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Investigations Platelet count decreased	2.0% 4/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Investigations Protein total decreased	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Investigations Protein total increased	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Investigations Red blood cell count decreased	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Investigations Residual urine volume increased	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Investigations Urine ketone body present	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Investigations Urine leukocyte esterase positive	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Investigations Vitamin D increased	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Investigations Weight decreased	8.1% 16/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	6.6% 13/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	8.1% 3/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Investigations Weight increased	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Investigations White blood cell count decreased	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Investigations White blood cell count increased	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Metabolism and nutrition disorders Acidosis	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Metabolism and nutrition disorders Decreased appetite	14.2% 28/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	8.6% 17/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	16.2% 6/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Metabolism and nutrition disorders Dehydration	6.6% 13/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	3.0% 6/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Metabolism and nutrition disorders Diabetes mellitus	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Metabolism and nutrition disorders Diabetes mellitus inadequate control	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Metabolism and nutrition disorders Failure to thrive	1.0% 2/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Metabolism and nutrition disorders Gout	1.5% 3/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	1.5% 3/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Metabolism and nutrition disorders Hypercalcaemia	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Metabolism and nutrition disorders Hyperchloraemia	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Metabolism and nutrition disorders Hypercholesterolaemia	2.5% 5/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	8.1% 3/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Metabolism and nutrition disorders Hyperglycaemia	5.6% 11/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	7.1% 14/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	5.4% 2/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Metabolism and nutrition disorders Hyperkalaemia	3.0% 6/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.0% 4/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Metabolism and nutrition disorders Hyperlipidaemia	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Metabolism and nutrition disorders Hypermagnesaemia	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Metabolism and nutrition disorders Hypernatraemia	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Metabolism and nutrition disorders Hypoalbuminaemia	1.5% 3/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.0% 4/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Reproductive system and breast disorders Pelvic pain	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Metabolism and nutrition disorders Hypocalcaemia	1.5% 3/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.0% 4/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Metabolism and nutrition disorders Hypokalaemia	6.6% 13/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	5.6% 11/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	5.4% 2/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Metabolism and nutrition disorders Hypomagnesaemia	2.0% 4/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.0% 4/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Metabolism and nutrition disorders Hyponatraemia	5.1% 10/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.0% 4/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	5.4% 2/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Metabolism and nutrition disorders Hypophosphataemia	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	1.0% 2/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Metabolism and nutrition disorders Increased appetite	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Metabolism and nutrition disorders Insulin resistance	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Metabolism and nutrition disorders Iron deficiency	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Metabolism and nutrition disorders Lactic acidosis	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Metabolism and nutrition disorders Malnutrition	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	1.0% 2/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Metabolism and nutrition disorders Metabolic acidosis	1.0% 2/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Metabolism and nutrition disorders Polydipsia	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Metabolism and nutrition disorders Type 1 diabetes mellitus	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Metabolism and nutrition disorders Type 2 diabetes mellitus	1.0% 2/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Metabolism and nutrition disorders Vitamin B complex deficiency	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Metabolism and nutrition disorders Vitamin B12 deficiency	1.5% 3/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Metabolism and nutrition disorders Vitamin D deficiency	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Musculoskeletal and connective tissue disorders Bone pain	3.0% 6/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	1.0% 2/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	5.4% 2/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Musculoskeletal and connective tissue disorders Bunion	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Musculoskeletal and connective tissue disorders Bursitis	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Musculoskeletal and connective tissue disorders Cervical spinal stenosis	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Musculoskeletal and connective tissue disorders Coccydynia	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Musculoskeletal and connective tissue disorders Costochondritis	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Musculoskeletal and connective tissue disorders Exostosis	1.0% 2/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Musculoskeletal and connective tissue disorders Flank pain	1.5% 3/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.5% 5/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Musculoskeletal and connective tissue disorders Foot deformity	1.0% 2/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Musculoskeletal and connective tissue disorders Groin pain	3.0% 6/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.0% 4/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Musculoskeletal and connective tissue disorders Intervertebral disc compression	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Musculoskeletal and connective tissue disorders Intervertebral disc degeneration	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Musculoskeletal and connective tissue disorders Joint crepitation	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	1.0% 2/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Musculoskeletal and connective tissue disorders Joint instability	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Musculoskeletal and connective tissue disorders Joint stiffness	1.0% 2/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Musculoskeletal and connective tissue disorders Joint swelling	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	1.0% 2/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Musculoskeletal and connective tissue disorders Limb discomfort	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Musculoskeletal and connective tissue disorders Lumbar spinal stenosis	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Musculoskeletal and connective tissue disorders Mobility decreased	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Musculoskeletal and connective tissue disorders Muscle atrophy	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Musculoskeletal and connective tissue disorders Muscle haemorrhage	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Musculoskeletal and connective tissue disorders Muscle spasms	3.6% 7/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	3.0% 6/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Musculoskeletal and connective tissue disorders Muscle tightness	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Musculoskeletal and connective tissue disorders Muscle twitching	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	6.6% 13/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.0% 4/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	5.4% 2/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Musculoskeletal and connective tissue disorders Musculoskeletal discomfort	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Musculoskeletal and connective tissue disorders Musculoskeletal disorder	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Musculoskeletal and connective tissue disorders Musculoskeletal stiffness	1.5% 3/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Musculoskeletal and connective tissue disorders Myalgia	5.1% 10/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.5% 5/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Musculoskeletal and connective tissue disorders Neck pain	2.5% 5/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.0% 4/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	5.4% 2/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Musculoskeletal and connective tissue disorders Osteoarthritis	3.6% 7/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Musculoskeletal and connective tissue disorders Osteolysis	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Musculoskeletal and connective tissue disorders Osteopenia	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Musculoskeletal and connective tissue disorders Osteoporosis	1.5% 3/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Musculoskeletal and connective tissue disorders Pain in jaw	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Musculoskeletal and connective tissue disorders Pathological fracture	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Musculoskeletal and connective tissue disorders Plantar fasciitis	1.5% 3/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Musculoskeletal and connective tissue disorders Psoriatic arthropathy	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Musculoskeletal and connective tissue disorders Rotator cuff syndrome	1.0% 2/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Musculoskeletal and connective tissue disorders Scoliosis	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Musculoskeletal and connective tissue disorders Spinal column stenosis	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Musculoskeletal and connective tissue disorders Spinal disorder	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Musculoskeletal and connective tissue disorders Spinal osteoarthritis	1.0% 2/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Musculoskeletal and connective tissue disorders Spinal pain	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Musculoskeletal and connective tissue disorders Spondylitis	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Musculoskeletal and connective tissue disorders Spondylolisthesis	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Musculoskeletal and connective tissue disorders Tendon disorder	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Musculoskeletal and connective tissue disorders Tendon pain	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Musculoskeletal and connective tissue disorders Tendonitis	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Musculoskeletal and connective tissue disorders Trigger finger	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Musculoskeletal and connective tissue disorders Vertebral foraminal stenosis	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Musculoskeletal and connective tissue disorders Arthritis	1.5% 3/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.0% 4/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Musculoskeletal and connective tissue disorders Inguinal mass	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	2.5% 5/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lipoma	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung adenocarcinoma	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to bone	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Plasma cell myeloma	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal oncocytoma	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Seborrhoeic keratosis	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Skin papilloma	1.0% 2/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Small cell lung cancer	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of skin	1.0% 2/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	1.0% 2/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Thyroid neoplasm	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour pain	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Nervous system disorders Altered state of consciousness	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Nervous system disorders Amnesia	3.6% 7/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	8.1% 3/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Nervous system disorders Aphasia	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Nervous system disorders Ataxia	1.0% 2/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Nervous system disorders Balance disorder	1.5% 3/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	5.4% 2/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Nervous system disorders Carotid artery occlusion	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Nervous system disorders Carpal tunnel syndrome	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Nervous system disorders Cerebellar infarction	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Nervous system disorders Cerebrovascular accident	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Nervous system disorders Cervical radiculopathy	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Nervous system disorders Cognitive disorder	1.0% 2/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Nervous system disorders Dementia	1.0% 2/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Nervous system disorders Depressed level of consciousness	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Nervous system disorders Diabetic neuropathy	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Nervous system disorders Disturbance in attention	1.0% 2/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Nervous system disorders Dysaesthesia	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Nervous system disorders Dysarthria	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Nervous system disorders Dysgeusia	4.1% 8/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	1.5% 3/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Nervous system disorders Encephalopathy	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Nervous system disorders Essential tremor	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Nervous system disorders Hemiparesis	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Nervous system disorders Hypersomnia	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Nervous system disorders Hypoaesthesia	2.0% 4/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	1.5% 3/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Nervous system disorders Hypogeusia	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Nervous system disorders Hyposmia	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Nervous system disorders Lethargy	1.0% 2/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Nervous system disorders Memory impairment	4.1% 8/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	1.5% 3/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Nervous system disorders Migraine	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Nervous system disorders Neuropathy peripheral	3.6% 7/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	5.4% 2/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Nervous system disorders Paraesthesia	4.1% 8/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.0% 4/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Nervous system disorders Parkinson's disease	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Nervous system disorders Parosmia	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Nervous system disorders Peripheral sensory neuropathy	1.0% 2/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Nervous system disorders Peroneal nerve palsy	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Nervous system disorders Presyncope	2.5% 5/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Nervous system disorders Restless legs syndrome	1.0% 2/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Nervous system disorders Sciatica	1.5% 3/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	1.0% 2/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Nervous system disorders Transient ischaemic attack	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Nervous system disorders Tremor	1.5% 3/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Nervous system disorders VIIth nerve paralysis	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Nervous system disorders Visual field defect	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Nervous system disorders Vocal cord paralysis	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Nervous system disorders Muscle spasticity	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Nervous system disorders Periodic limb movement disorder	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Nervous system disorders Post-traumatic headache	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Psychiatric disorders Abnormal dreams	1.0% 2/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Psychiatric disorders Agitation	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Psychiatric disorders Alcoholism	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Psychiatric disorders Apathy	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Psychiatric disorders Confusional state	3.0% 6/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	1.0% 2/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Psychiatric disorders Delirium	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	1.0% 2/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Psychiatric disorders Depressed mood	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	1.0% 2/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Psychiatric disorders Disorientation	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Psychiatric disorders Emotional distress	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Psychiatric disorders Hallucination	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Psychiatric disorders Libido decreased	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Psychiatric disorders Mental status changes	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Psychiatric disorders Mood altered	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Psychiatric disorders Mood swings	1.0% 2/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Psychiatric disorders Nervousness	1.5% 3/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Psychiatric disorders Personality change	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Psychiatric disorders Restlessness	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Psychiatric disorders Sleep disorder	1.5% 3/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Psychiatric disorders Sleep terror	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Psychiatric disorders Suicidal ideation	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Renal and urinary disorders Bladder neck obstruction	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Renal and urinary disorders Bladder outlet obstruction	1.0% 2/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Renal and urinary disorders Bladder spasm	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	1.5% 3/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Renal and urinary disorders Calculus bladder	1.0% 2/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Renal and urinary disorders Chromaturia	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Renal and urinary disorders Cystitis noninfective	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Renal and urinary disorders Dysuria	1.0% 2/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	3.5% 7/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Renal and urinary disorders Enuresis	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Renal and urinary disorders Haemorrhage urinary tract	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Renal and urinary disorders Hydronephrosis	3.0% 6/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	4.0% 8/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Renal and urinary disorders Hypertonic bladder	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Renal and urinary disorders Incontinence	1.0% 2/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Renal and urinary disorders Microalbuminuria	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Renal and urinary disorders Micturition urgency	4.6% 9/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Renal and urinary disorders Nephrolithiasis	1.5% 3/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Renal and urinary disorders Nocturia	1.5% 3/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.0% 4/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	5.4% 2/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Renal and urinary disorders Oliguria	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Renal and urinary disorders Pneumaturia	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Renal and urinary disorders Pollakiuria	5.6% 11/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	3.5% 7/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Renal and urinary disorders Proteinuria	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Renal and urinary disorders Pyuria	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Renal and urinary disorders Renal cyst	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Renal and urinary disorders Renal failure	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	1.5% 3/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Renal and urinary disorders Renal failure chronic	1.5% 3/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Renal and urinary disorders Renal impairment	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	1.0% 2/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Renal and urinary disorders Renal pain	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Renal and urinary disorders Stress urinary incontinence	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Renal and urinary disorders Urethral haemorrhage	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Renal and urinary disorders Urethral stenosis	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	1.0% 2/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Renal and urinary disorders Urethritis noninfective	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Renal and urinary disorders Urge incontinence	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Renal and urinary disorders Urinary hesitation	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Renal and urinary disorders Urinary incontinence	5.1% 10/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	4.0% 8/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Renal and urinary disorders Urinary retention	2.5% 5/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	3.5% 7/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Renal and urinary disorders Urinary tract obstruction	1.5% 3/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	1.5% 3/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Renal and urinary disorders Urine flow decreased	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Reproductive system and breast disorders Balanoposthitis	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Reproductive system and breast disorders Benign prostatic hyperplasia	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Reproductive system and breast disorders Breast pain	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Reproductive system and breast disorders Breast tenderness	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Reproductive system and breast disorders Erectile dysfunction	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Reproductive system and breast disorders Genital discomfort	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Reproductive system and breast disorders Genital lesion	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Reproductive system and breast disorders Genital rash	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Reproductive system and breast disorders Gynaecomastia	1.0% 2/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	1.0% 2/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Reproductive system and breast disorders Nipple pain	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Reproductive system and breast disorders Penile oedema	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Reproductive system and breast disorders Penile swelling	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Reproductive system and breast disorders Priapism	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Reproductive system and breast disorders Prostatic pain	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Reproductive system and breast disorders Prostatitis	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Reproductive system and breast disorders Prostatomegaly	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Reproductive system and breast disorders Scrotal swelling	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Reproductive system and breast disorders Testicular pain	2.0% 4/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	1.0% 2/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Respiratory, thoracic and mediastinal disorders Alveolar lung disease	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Respiratory, thoracic and mediastinal disorders Aspiration	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Respiratory, thoracic and mediastinal disorders Atelectasis	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	1.0% 2/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	1.0% 2/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Respiratory, thoracic and mediastinal disorders Cough	7.1% 14/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	4.5% 9/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Respiratory, thoracic and mediastinal disorders Dysphonia	2.5% 5/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	2.5% 5/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	1.0% 2/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Respiratory, thoracic and mediastinal disorders Dyspnoea paroxysmal nocturnal	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Respiratory, thoracic and mediastinal disorders Emphysema	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Respiratory, thoracic and mediastinal disorders Epistaxis	1.5% 3/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Respiratory, thoracic and mediastinal disorders Hiccups	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	1.0% 2/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Respiratory, thoracic and mediastinal disorders Increased upper airway secretion	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Respiratory, thoracic and mediastinal disorders Nasal congestion	2.0% 4/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	1.5% 3/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Respiratory, thoracic and mediastinal disorders Nasal dryness	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	3.0% 6/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Respiratory, thoracic and mediastinal disorders Pleural effusion	1.0% 2/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	1.0% 2/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	1.0% 2/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Respiratory, thoracic and mediastinal disorders Productive cough	2.5% 5/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	1.0% 2/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Respiratory, thoracic and mediastinal disorders Pulmonary fibrosis	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Respiratory, thoracic and mediastinal disorders Pulmonary hypertension	1.0% 2/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Respiratory, thoracic and mediastinal disorders Pulmonary vascular disorder	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Respiratory, thoracic and mediastinal disorders Rales	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Respiratory, thoracic and mediastinal disorders Respiratory disorder	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	1.0% 2/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Respiratory, thoracic and mediastinal disorders Respiratory tract congestion	1.0% 2/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Respiratory, thoracic and mediastinal disorders Rhinitis allergic	1.0% 2/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	1.5% 3/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Respiratory, thoracic and mediastinal disorders Rhonchi	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Respiratory, thoracic and mediastinal disorders Sinus congestion	1.0% 2/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Respiratory, thoracic and mediastinal disorders Sinus disorder	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Respiratory, thoracic and mediastinal disorders Sleep apnoea syndrome	2.5% 5/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Respiratory, thoracic and mediastinal disorders Throat irritation	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Respiratory, thoracic and mediastinal disorders Upper-airway cough syndrome	2.0% 4/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Respiratory, thoracic and mediastinal disorders Wheezing	1.0% 2/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	1.0% 2/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Skin and subcutaneous tissue disorders Actinic keratosis	1.5% 3/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	1.0% 2/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Skin and subcutaneous tissue disorders Alopecia	2.0% 4/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	1.0% 2/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Skin and subcutaneous tissue disorders Blister	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Skin and subcutaneous tissue disorders Decubitus ulcer	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	1.0% 2/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Skin and subcutaneous tissue disorders Dermatitis allergic	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Skin and subcutaneous tissue disorders Dermatitis contact	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Skin and subcutaneous tissue disorders Diabetic foot	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Skin and subcutaneous tissue disorders Dry skin	2.5% 5/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	1.5% 3/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Skin and subcutaneous tissue disorders Ecchymosis	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Skin and subcutaneous tissue disorders Eczema	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Skin and subcutaneous tissue disorders Erythema	1.5% 3/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Skin and subcutaneous tissue disorders Hair growth abnormal	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Skin and subcutaneous tissue disorders Hyperhidrosis	3.6% 7/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	1.0% 2/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Skin and subcutaneous tissue disorders Hyperkeratosis	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Skin and subcutaneous tissue disorders Ingrowing nail	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Skin and subcutaneous tissue disorders Lentigo	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Skin and subcutaneous tissue disorders Night sweats	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	1.0% 2/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Skin and subcutaneous tissue disorders Pain of skin	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Skin and subcutaneous tissue disorders Photodermatosis	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Skin and subcutaneous tissue disorders Pigmentation disorder	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Skin and subcutaneous tissue disorders Pruritus	2.5% 5/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	1.5% 3/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Skin and subcutaneous tissue disorders Psoriasis	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Skin and subcutaneous tissue disorders Rash generalised	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Skin and subcutaneous tissue disorders Rash macular	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Skin and subcutaneous tissue disorders Rash maculo-papular	1.0% 2/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Skin and subcutaneous tissue disorders Rash pruritic	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Skin and subcutaneous tissue disorders Skin discolouration	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Skin and subcutaneous tissue disorders Skin disorder	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Skin and subcutaneous tissue disorders Skin hypopigmentation	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Skin and subcutaneous tissue disorders Skin lesion	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Skin and subcutaneous tissue disorders Skin ulcer	1.0% 2/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Skin and subcutaneous tissue disorders Swelling face	1.0% 2/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Surgical and medical procedures Cataract operation	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Surgical and medical procedures Skin neoplasm excision	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Vascular disorders Accelerated hypertension	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Vascular disorders Aortic arteriosclerosis	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Vascular disorders Arteriovenous fistula	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Vascular disorders Blood pressure inadequately controlled	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Vascular disorders Deep vein thrombosis	1.5% 3/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Vascular disorders Flushing	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Vascular disorders Haematoma	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Vascular disorders Hypotension	2.0% 4/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.5% 5/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	10.8% 4/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Vascular disorders Intermittent claudication	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Vascular disorders Jugular vein thrombosis	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Vascular disorders Orthostatic hypotension	1.0% 2/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	1.0% 2/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Vascular disorders Peripheral arterial occlusive disease	1.0% 2/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Vascular disorders Peripheral artery stenosis	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Vascular disorders Peripheral coldness	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Vascular disorders Peripheral ischaemia	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Vascular disorders Peripheral vascular disorder	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	1.0% 2/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Vascular disorders Thrombophlebitis superficial	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Vascular disorders Thrombosis	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Vascular disorders Varicose vein	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Vascular disorders Aortic aneurysm	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Injury, poisoning and procedural complications Bone contusion	1.5% 3/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Investigations Haematocrit decreased	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Investigations Blood urea increased	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	1.0% 2/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Investigations Hepatic enzyme increased	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Nervous system disorders Syncope	3.6% 7/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	1.5% 3/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Cardiac disorders Angina pectoris	1.0% 2/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Cardiac disorders Aortic valve disease	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Cardiac disorders Aortic valve stenosis	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Cardiac disorders Arrhythmia	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Cardiac disorders Arteriosclerosis coronary artery	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Cardiac disorders Atrial fibrillation	2.0% 4/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.5% 5/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	8.1% 3/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Cardiac disorders Atrial flutter	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Cardiac disorders Atrial thrombosis	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Cardiac disorders Atrioventricular block second degree	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Cardiac disorders Bradycardia	1.0% 2/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	1.0% 2/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Cardiac disorders Cardiac failure congestive	2.0% 4/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	1.5% 3/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	5.4% 2/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Cardiac disorders Cardiomegaly	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Cardiac disorders Coronary artery disease	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Cardiac disorders Mitral valve incompetence	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Cardiac disorders Myocardial ischaemia	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Cardiac disorders Palpitations	1.0% 2/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Cardiac disorders Sick sinus syndrome	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Cardiac disorders Sinus bradycardia	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Cardiac disorders Sinus tachycardia	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Cardiac disorders Supraventricular tachycardia	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Cardiac disorders Tachycardia	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	1.5% 3/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Cardiac disorders Ventricular extrasystoles	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Cardiac disorders Ventricular tachycardia	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Eye disorders Astigmatism	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Eye disorders Cataract	2.0% 4/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	1.5% 3/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Eye disorders Cataract nuclear	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Eye disorders Conjunctivitis	1.5% 3/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Eye disorders Diabetic retinopathy	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Eye disorders Dry eye	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	2.7% 1/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Eye disorders Eye irritation	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Eye disorders Eye pain	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Eye disorders Eye pruritus	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Eye disorders Lacrimation increased	1.5% 3/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Eye disorders Macular degeneration	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Eye disorders Ocular hyperaemia	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Eye disorders Photophobia	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Eye disorders Posterior capsule opacification	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Eye disorders Retinal tear	0.00% 0/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Eye disorders Vision blurred	2.0% 4/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	1.0% 2/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Eye disorders Visual impairment	2.0% 4/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study
Cardiac disorders Cardiomyopathy	0.51% 1/197 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.51% 1/198 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study	0.00% 0/37 • From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer Inc.

Phone: 1-800-718-1021

Email: ClinicalTrials.gov_Inquiries@pfizer.com

Results disclosure agreements

• Principal investigator is a sponsor employee PI agrees not to independently publish the results before the publication of the multi-center PI paper. Sponsor shall review and comment 30 days prior to submission or disclosure. If publication or disclosure contains Sponsor Confidential Information, other than study data, PI agrees to remove Confidential Information from publication or disclosure. Sponsor may request that PI delay such publication for an additional 60 days to protect the patentability of any invention described.
• Publication restrictions are in place

Restriction type: OTHER