Trial Outcomes & Findings for An Efficacy Study of Teriflunomide in Participants With Relapsing Multiple Sclerosis (NCT NCT00751881)

NCT ID: NCT00751881

Last Updated: 2016-07-07

Results Overview

ARR is obtained from the total number of confirmed relapses that occurred during the treatment period divided by the sum of treatment durations. Each episode of relapse - appearance, or worsening of a clinical symptom that was stable for at least 30 days, that persisted for a minimum of 24 hours in the absence of fever - was to be confirmed by an increase in Expanded Disability Status Scale (EDSS) score or Functional System scores. To account for the different treatment durations among participants, a Poisson regression model with robust error variance was used (total number of confirmed relapses as response variable; log-transformed treatment duration as "offset" variable; treatment group, region of enrollment and baseline EDSS stratum as covariates).

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 1169 participants
• Primary outcome timeframe: Core treatment period between 48 - 152 weeks depending on time of enrollment
• Results posted on: 2016-07-07

Participant Flow

A total of 1493 participants were screened at 193 sites in 26 countries. The common end date for core treatment period was on 17 April 2012 (maximum treatment duration of 173 weeks). The extension study was completed on 18 June 2015 (maximum treatment duration was 174 weeks in addition to core treatment period).

Randomization was stratified by investigational site and Expanded Disability Status Scale (EDSS) score ≤3.5 or >3.5). Assignment to groups was done using an Interactive Voice Response System(IVRS) in 1:1:1 ratio. 1169 participants were randomized at 190 sites. 780 participants completed core treatment period and 751 were treated in extension study.

Participant milestones

Measure	Placebo / Teriflunomide 14 mg Core treatment period: Placebo (for teriflunomide) once daily. Extension treatment period: Teriflunomide 14 mg once daily.	Teriflunomide 7 mg / 14 mg Core treatment period: Teriflunomide 7 mg once daily. Extension treatment period: Teriflunomide 14 mg once daily.	Teriflunomide 14 mg / 14 mg Core treatment period: Teriflunomide 14 mg once daily. Extension treatment period: Teriflunomide 14 mg once daily.
Core Treatment Period STARTED	389	408	372
Core Treatment Period Treated	388	407	370
Core Treatment Period COMPLETED	263	273	244
Core Treatment Period NOT COMPLETED	126	135	128
Extension Study Period STARTED	253	265	233
Extension Study Period COMPLETED	188	194	167
Extension Study Period NOT COMPLETED	65	71	66

Reasons for withdrawal

Measure	Placebo / Teriflunomide 14 mg Core treatment period: Placebo (for teriflunomide) once daily. Extension treatment period: Teriflunomide 14 mg once daily.	Teriflunomide 7 mg / 14 mg Core treatment period: Teriflunomide 7 mg once daily. Extension treatment period: Teriflunomide 14 mg once daily.	Teriflunomide 14 mg / 14 mg Core treatment period: Teriflunomide 14 mg once daily. Extension treatment period: Teriflunomide 14 mg once daily.
Core Treatment Period Not treated	1	1	2
Core Treatment Period Adverse Event	26	54	58
Core Treatment Period Lack of Efficacy	37	30	20
Core Treatment Period Poor compliance to protocol	15	3	4
Core Treatment Period Lost to Follow-up	6	4	3
Core Treatment Period Other: protocol deviation	3	3	7
Core Treatment Period Other: wish to parent	5	7	4
Core Treatment Period Other: personal/family constraints	6	7	10
Core Treatment Period Other: MS treatment change	6	4	4
Core Treatment Period Other: tolerability complaints	2	0	0
Core Treatment Period Other:participant's decision/unspecified	19	22	16
Extension Study Period Adverse Event	18	20	21
Extension Study Period Lack of Efficacy	14	10	20
Extension Study Period Lost to Follow-up	4	9	6
Extension Study Period Poor Compliance to Protocol	3	2	1
Extension Study Period Other than specified above	26	30	18

Baseline Characteristics

An Efficacy Study of Teriflunomide in Participants With Relapsing Multiple Sclerosis

Baseline characteristics by cohort

Measure	Placebo / Teriflunomide 14 mg n=389 Participants Core treatment period: Placebo once daily. Extension treatment period: Teriflunomide 14 mg once daily.	Teriflunomide 7 mg / 14 mg n=408 Participants Core treatment period: Teriflunomide 7 mg once daily. Extension treatment period: Teriflunomide 14 mg once daily.	Teriflunomide 14 mg / 14 mg n=372 Participants Core treatment period: Teriflunomide 14 mg once daily. Extension treatment period: Teriflunomide 14 mg once daily.	Total n=1169 Participants Total of all reporting groups
Age, Continuous	38.1 years STANDARD_DEVIATION 9.1 • n=113 Participants	37.4 years STANDARD_DEVIATION 9.4 • n=163 Participants	38.2 years STANDARD_DEVIATION 9.4 • n=160 Participants	37.9 years STANDARD_DEVIATION 9.3 • n=483 Participants
Sex: Female, Male Female	273 Participants n=113 Participants	300 Participants n=163 Participants	258 Participants n=160 Participants	831 Participants n=483 Participants
Sex: Female, Male Male	116 Participants n=113 Participants	108 Participants n=163 Participants	114 Participants n=160 Participants	338 Participants n=483 Participants
Region of Enrollment Eastern Europe	117 participants n=113 Participants	124 participants n=163 Participants	116 participants n=160 Participants	357 participants n=483 Participants
Region of Enrollment Western Europe and Africa	121 participants n=113 Participants	127 participants n=163 Participants	120 participants n=160 Participants	368 participants n=483 Participants
Region of Enrollment Asia and Australia	67 participants n=113 Participants	65 participants n=163 Participants	55 participants n=160 Participants	187 participants n=483 Participants
Region of Enrollment America	84 participants n=113 Participants	92 participants n=163 Participants	81 participants n=160 Participants	257 participants n=483 Participants
Time since first diagnosis of Multiple Sclerosis (MS)	4.92 years STANDARD_DEVIATION 5.66 • n=113 Participants	5.30 years STANDARD_DEVIATION 5.45 • n=163 Participants	5.27 years STANDARD_DEVIATION 5.90 • n=160 Participants	5.16 years STANDARD_DEVIATION 5.66 • n=483 Participants
Number of MS relapses Within the past year	1 relapses n=113 Participants	1 relapses n=163 Participants	1 relapses n=160 Participants	1 relapses n=483 Participants
Number of MS relapses Within the past 2 years	2 relapses n=113 Participants	2 relapses n=163 Participants	2 relapses n=160 Participants	2 relapses n=483 Participants
Time since most recent MS relapse onset	5.29 months STANDARD_DEVIATION 3.41 • n=113 Participants	5.18 months STANDARD_DEVIATION 3.41 • n=163 Participants	5.33 months STANDARD_DEVIATION 3.32 • n=160 Participants	5.26 months STANDARD_DEVIATION 3.38 • n=483 Participants
MS subtype Relapsing Remitting	379 participants n=113 Participants	393 participants n=163 Participants	366 participants n=160 Participants	1138 participants n=483 Participants
MS subtype Secondary Progressive	4 participants n=113 Participants	3 participants n=163 Participants	2 participants n=160 Participants	9 participants n=483 Participants
MS subtype Progressive Relapsing	6 participants n=113 Participants	12 participants n=163 Participants	2 participants n=160 Participants	20 participants n=483 Participants
MS subtype Information not available	0 participants n=113 Participants	0 participants n=163 Participants	2 participants n=160 Participants	2 participants n=483 Participants
Baseline EDSS score ≤3.5	294 participants n=113 Participants	301 participants n=163 Participants	276 participants n=160 Participants	871 participants n=483 Participants
Baseline EDSS score >3.5	95 participants n=113 Participants	107 participants n=163 Participants	96 participants n=160 Participants	298 participants n=483 Participants

PRIMARY outcome

Timeframe: Core treatment period between 48 - 152 weeks depending on time of enrollment

Population: Intent-to-treat population: all randomized and treated participants. Participants were considered in the treatment group to which they were randomized regardless of the drug they actually received.

ARR is obtained from the total number of confirmed relapses that occurred during the treatment period divided by the sum of treatment durations.

Each episode of relapse - appearance, or worsening of a clinical symptom that was stable for at least 30 days, that persisted for a minimum of 24 hours in the absence of fever - was to be confirmed by an increase in Expanded Disability Status Scale (EDSS) score or Functional System scores.

To account for the different treatment durations among participants, a Poisson regression model with robust error variance was used (total number of confirmed relapses as response variable; log-transformed treatment duration as "offset" variable; treatment group, region of enrollment and baseline EDSS stratum as covariates).

Outcome measures

Measure	Placebo n=388 Participants Placebo once daily	Teriflunomide 7 mg n=407 Participants Teriflunomide 7 mg once daily	Teriflunomide 14 mg n=370 Participants Teriflunomide 14 mg once daily
Core Treatment Period: Annualized Relapse Rate (ARR): Poisson Regression Estimate	0.501 relapses per year Interval 0.432 to 0.581	0.389 relapses per year Interval 0.332 to 0.457	0.319 relapses per year Interval 0.267 to 0.381

SECONDARY outcome

Timeframe: Core treatment period between 48 - 152 weeks depending on time of enrollment

Population: Intent-to-treat population

Probability of disability progression at 24, 48, 108 and 132 weeks was estimated using Kaplan-Meier method on the time to disability progression defined as the time from randomization to first 12-week sustained disability progression [i.e. increase from baseline of at least 1 point in EDSS score (at least 0.5 point for participants with baseline EDSS score >5.5) that persisted for at least 12 weeks].

Participants free of disability progression (no disability progression observed on treatment) were censored at the date of the last on-treatment EDSS evaluation.

Kaplan-Meier method consists in computing probabilities of non occurrence of event at any observed time of event and multiplying successive probabilities for time ≤t by any earlier computed probabilities to estimate the probability of being event-free for the amount of time t. Probability of event at time t is 1 minus the probability of being event-free for the amount of time t.

Outcome measures

Measure	Placebo n=388 Participants Placebo once daily	Teriflunomide 7 mg n=407 Participants Teriflunomide 7 mg once daily	Teriflunomide 14 mg n=370 Participants Teriflunomide 14 mg once daily
Core Treatment Period: Time to Disability Progression Probability of disability progression at 24 weeks	8.0 percent probability Interval 5.2 to 10.7	5.3 percent probability Interval 3.0 to 7.6	2.7 percent probability Interval 0.9 to 4.4
Core Treatment Period: Time to Disability Progression Probability of disability progression at 48 weeks	14.2 percent probability Interval 10.6 to 17.9	12.1 percent probability Interval 8.7 to 15.5	7.8 percent probability Interval 4.9 to 10.8
Core Treatment Period: Time to Disability Progression Probability of disability progression at 108 weeks	19.7 percent probability Interval 15.2 to 24.1	21.1 percent probability Interval 16.1 to 26.1	15.8 percent probability Interval 11.2 to 20.4
Core Treatment Period: Time to Disability Progression Probability of disability progression at 132 weeks	21.0 percent probability Interval 15.9 to 26.0	22.2 percent probability Interval 16.8 to 27.6	15.8 percent probability Interval 11.2 to 20.4

SECONDARY outcome

Timeframe: Core treatment period between 48 - 152 weeks depending on time of enrollment

Population: Intent-to-treat population

Probability of no relapse at 24, 48, 108 and 132 weeks was estimated using Kaplan-Meier method on the time to relapse defined as the time from randomization to first EDSS confirmed relapse.

Participants free of confirmed relapse (no EDSS confirmed relapse observed on treatment) were censored at the date of the last study drug intake.

Outcome measures

Measure	Placebo n=388 Participants Placebo once daily	Teriflunomide 7 mg n=407 Participants Teriflunomide 7 mg once daily	Teriflunomide 14 mg n=370 Participants Teriflunomide 14 mg once daily
Core Treatment Period: Time Without Relapse Probability of no relapse at 24 weeks	76.4 percent probability Interval 72.1 to 80.7	81.5 percent probability Interval 77.6 to 85.4	85.5 percent probability Interval 81.8 to 89.2
Core Treatment Period: Time Without Relapse Probability of no relapse at 48 weeks	60.6 percent probability Interval 55.5 to 65.6	71.9 percent probability Interval 67.3 to 76.5	76.3 percent probability Interval 71.7 to 81.0
Core Treatment Period: Time Without Relapse Probability of no relapse at 108 weeks	46.8 percent probability Interval 41.0 to 52.6	58.2 percent probability Interval 52.6 to 63.8	57.1 percent probability Interval 50.5 to 63.7
Core Treatment Period: Time Without Relapse Probability of no relapse at 132 weeks	37.7 percent probability Interval 30.2 to 45.2	55.4 percent probability Interval 48.8 to 62.0	51.5 percent probability Interval 43.6 to 59.5

SECONDARY outcome

Timeframe: Baseline (before randomization), Week 12, Week 24, Week 36 and Week 48

Population: Intent-to-treat population

EDSS is an ordinal scale in half-point increments that qualifies disability in participants with MS. It consists of 8 ordinal rating scales assessing 7 functional systems (visual, brainstem, pyramidal, cerebellar, sensory, bowel/bladder and cerebral) as well as ambulation.

EDSS total score ranges from 0 (normal neurological examination) to 10 (death due to MS).

Baseline adjusted least-squares means at Week 48 were estimated using a Mixed-effect model with repeated measures (MMRM) on EDSS score data (treatment group, region of enrollment, baseline EDSS stratum, visit, treatment-by-visit interaction, baseline value, and baseline-by-visit interaction as factors). All the timepoints from randomization up to Week 48 were included in the model.

Outcome measures

Measure	Placebo n=388 Participants Placebo once daily	Teriflunomide 7 mg n=407 Participants Teriflunomide 7 mg once daily	Teriflunomide 14 mg n=370 Participants Teriflunomide 14 mg once daily
Core Treatment Period: Change From Baseline to Week 48 in EDSS Total Score	0.089 units on a scale Standard Error 0.050	0.042 units on a scale Standard Error 0.049	-0.050 units on a scale Standard Error 0.052

SECONDARY outcome

Timeframe: Baseline (before randomization), Week 12, Week 24 and Week 48

Population: Intent-to-treat population

FIS is a participants-reported scale that qualifies the impact of fatigue on daily life in participants with MS. It consists of 40 statements that measure fatigue in 3 areas; physical, cognitive, and social.

FIS total score ranges from 0 (no problem) to 160 (extreme problem).

Baseline adjusted least-squares means at week 48 were estimated using a Mixed-effect model with repeated measures (MMRM) on FIS total score data (treatment group, region of enrollment, baseline EDSS stratum, visit, treatment-by-visit interaction, baseline value, and baseline-by-visit interaction as factors). All the timepoints from randomization up to Week 48 were included in the model.

Outcome measures

Measure	Placebo n=388 Participants Placebo once daily	Teriflunomide 7 mg n=407 Participants Teriflunomide 7 mg once daily	Teriflunomide 14 mg n=370 Participants Teriflunomide 14 mg once daily
Core Treatment Period: Change From Baseline to Week 48 in Fatigue Impact Scale (FIS) Total Score	4.669 units on a scale Standard Error 1.576	2.512 units on a scale Standard Error 1.533	1.915 units on a scale Standard Error 1.628

SECONDARY outcome

Timeframe: Baseline (before randomization) and up to Week 152

Population: Intent-to-treat population

Baseline adjusted least-squares means at last visit were estimated using an analysis of covariance (ANCOVA) model on collected data for FIS total score (treatment group, region of enrollment, baseline EDSS stratum, visit number for the last visit and baseline value as factors).

Outcome measures

Measure	Placebo n=388 Participants Placebo once daily	Teriflunomide 7 mg n=407 Participants Teriflunomide 7 mg once daily	Teriflunomide 14 mg n=370 Participants Teriflunomide 14 mg once daily
Core Treatment Period: Change From Baseline to Last Visit in Fatigue Impact Scale (FIS) Total Score	6.311 units on a scale Standard Error 1.671	4.464 units on a scale Standard Error 1.657	2.043 units on a scale Standard Error 1.682

SECONDARY outcome

Timeframe: Baseline (before randomization), Week 12, Week 24 and Week 48

Population: Intent-to-treat population

SF-36 scale is a generic, self-administered, health-related quality-of-life (QOL) instrument. It is constructed such that the 36 questions represent 8 of the most important health concepts: physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health.

Two summary scores are obtained:

• the physical health component summary score,
• the mental health component summary score.

Both scores range from 0 to 100 and a high score indicates a more favorable health state.

Baseline adjusted least-squares means at week 48 were estimated using a Mixed-effect model with repeated measures [MMRM] on each summary score data (treatment group, region of enrollment, baseline EDSS stratum, visit, treatment-by-visit interaction, baseline value, and baseline-by-visit interaction as factors). All the timepoints from randomization up to Week 48 were included in the model.

Outcome measures

Measure	Placebo n=388 Participants Placebo once daily	Teriflunomide 7 mg n=407 Participants Teriflunomide 7 mg once daily	Teriflunomide 14 mg n=370 Participants Teriflunomide 14 mg once daily
Core Treatment Period: Change From Baseline to Week 48 in Short Form Generic Health Survey - 36 Items (SF-36) Summary Scores Physical health component	-1.082 units on a scale Standard Error 0.405	-0.397 units on a scale Standard Error 0.396	-0.105 units on a scale Standard Error 0.418
Core Treatment Period: Change From Baseline to Week 48 in Short Form Generic Health Survey - 36 Items (SF-36) Summary Scores Mental health component	-2.913 units on a scale Standard Error 0.586	-2.031 units on a scale Standard Error 0.571	-1.434 units on a scale Standard Error 0.606

SECONDARY outcome

Timeframe: Baseline (before randomization) and up to Week 152

Population: Intent-to-treat population

Baseline adjusted least-squares means at last visit were estimated using an analysis of covariance (ANCOVA) model on collected data for each summary score (treatment group, region of enrollment, baseline EDSS stratum, visit number for the last visit and baseline value as factors).

Outcome measures

Measure	Placebo n=388 Participants Placebo once daily	Teriflunomide 7 mg n=407 Participants Teriflunomide 7 mg once daily	Teriflunomide 14 mg n=370 Participants Teriflunomide 14 mg once daily
Core Treatment Period: Change From Baseline to Last Visit in Short Form Generic Health Survey - 36 Items (SF-36) Summary Scores Physical Health component	-1.629 units on a scale Standard Error 0.435	-0.909 units on a scale Standard Error 0.441	-0.638 units on a scale Standard Error 0.436
Core Treatment Period: Change From Baseline to Last Visit in Short Form Generic Health Survey - 36 Items (SF-36) Summary Scores Mental Health component	-2.792 units on a scale Standard Error 0.592	-1.704 units on a scale Standard Error 0.597	-1.087 units on a scale Standard Error 0.593

SECONDARY outcome

Timeframe: From first study drug intake up to 112 days after last intake in the core treatment period or up to first intake in the extension treatment period, whichever occurred first

Population: All randomized and treated participants. Participants were considered according to the drug actually received. The 3 participants in the placebo group who received teriflunomide were analyzed according to the teriflunomide dose. The participant in the teriflunomide 14 mg group who received 7 mg was analyzed in the teriflunomide 7 mg group.

Adverse Events (AE) are any unfavorable and unintended sign, symptom, syndrome, or illness observed by the investigator or reported by the participant during the study.

Outcome measures

Measure	Placebo n=385 Participants Placebo once daily	Teriflunomide 7 mg n=409 Participants Teriflunomide 7 mg once daily	Teriflunomide 14 mg n=371 Participants Teriflunomide 14 mg once daily
Core Treatment Period: Overview of Adverse Events Any AE	320 participants	344 participants	320 participants
Core Treatment Period: Overview of Adverse Events - Any serious AE	47 participants	52 participants	44 participants
Core Treatment Period: Overview of Adverse Events - Any AE leading to death	1 participants	1 participants	2 participants
Core Treatment Period: Overview of Adverse Events - Any AE leading to treatment discontinuation	24 participants	53 participants	58 participants

SECONDARY outcome

Timeframe: From first intake of study drug in extension treatment period up to 28 days after the last intake in the extension treatment period

Population: Safety population: all randomized participants who received at least 1 dose of investigational product. Two participants in placebo of core study received teriflunomide and were analyzed according to teriflunomide dose. One participant in teriflunomide 14 mg in core study group who received 7 mg was analyzed in teriflunomide 7 mg group.

AEs were any unfavourable and unintended sign, symptom, syndrome, or illness observed by the investigator or reported by the participant during the study.

Outcome measures

Measure	Placebo n=251 Participants Placebo once daily	Teriflunomide 7 mg n=267 Participants Teriflunomide 7 mg once daily	Teriflunomide 14 mg n=233 Participants Teriflunomide 14 mg once daily
Extension Treatment Period: Overview of Treatment Emergent Adverse Events (TEAE) Any TEAE	203 participants	200 participants	188 participants
Extension Treatment Period: Overview of Treatment Emergent Adverse Events (TEAE) Any serious TEAE	16 participants	33 participants	29 participants
Extension Treatment Period: Overview of Treatment Emergent Adverse Events (TEAE) Any TEAE leading to death	1 participants	3 participants	1 participants
Extension Treatment Period: Overview of Treatment Emergent Adverse Events (TEAE) Any TEAE leading to treatment discontinuation	17 participants	17 participants	20 participants

SECONDARY outcome

Timeframe: Core treatment period (maximum: 173 weeks) and Extension treatment period (maximum: 174 weeks)

Population: ITT population for extension treatment period consists of all participants with a signed informed consent form for the extension and with a date of treatment allocated or recorded in the IVRS/IWRS database, regardless of whether the treatment was actually taken.

Probability of disability progression since the randomization of the core period was estimated using Kaplan-Meier method on the time to disability progression defined as the time from randomization to first 12 week sustained disability progression [i.e. increase from baseline of at least 1 point in EDSS score (at least 0.5 point for participants with baseline EDSS score >5.5) that persisted for at least 12 weeks].

Participants free of disability progression (no disability progression observed on treatment) were censored at the date of the last on-treatment EDSS evaluation.

Kaplan-Meier method consists in computing probabilities of non occurrence of event at any observed time of event and multiplying successive probabilities for time ≤t by any earlier computed probabilities to estimate the probability of being event free for the amount of time t. Probability of event at time t was 1 minus the probability of being event-free for the amount of time t.

Outcome measures

Measure	Placebo n=253 Participants Placebo once daily	Teriflunomide 7 mg n=265 Participants Teriflunomide 7 mg once daily	Teriflunomide 14 mg n=233 Participants Teriflunomide 14 mg once daily
Extension Treatment Period: Time to Disability Progression 1 year	0.130 percent probability Interval 0.089 to 0.172	0.117 percent probability Interval 0.078 to 0.156	0.077 percent probability Interval 0.043 to 0.112
Extension Treatment Period: Time to Disability Progression 2 year	0.190 percent probability Interval 0.142 to 0.238	0.175 percent probability Interval 0.129 to 0.221	0.147 percent probability Interval 0.101 to 0.192
Extension Treatment Period: Time to Disability Progression 3 year	0.245 percent probability Interval 0.191 to 0.299	0.233 percent probability Interval 0.181 to 0.285	0.190 percent probability Interval 0.139 to 0.241
Extension Treatment Period: Time to Disability Progression 4 year	0.307 percent probability Interval 0.246 to 0.368	0.270 percent probability Interval 0.214 to 0.326	0.248 percent probability Interval 0.189 to 0.307
Extension Treatment Period: Time to Disability Progression 5 year	0.328 percent probability Interval 0.262 to 0.395	0.317 percent probability Interval 0.25 to 0.384	0.265 percent probability Interval 0.203 to 0.327

SECONDARY outcome

Timeframe: Extension treatment period (Maximum: 174 weeks)

Population: ITT population for extension treatment period consists of all participants with a signed informed consent form for the extension and with a date of treatment allocated or recorded in the IVRS/IWRS database, regardless of whether the treatment was actually taken.

ARR was obtained from the total number of confirmed relapses that occurred during the treatment period divided by the sum of treatment durations. A relapse is defined as the appearance of a new clinical sign/symptom or clinical worsening of a previous sign/symptom (one that had been stable for at least 30 days) that persists for a minimum of 24 hours in the absence of fever. Relapse was confirmed by an increase in EDSS score or Functional System scores. To account for the different treatment durations among participants, a Poisson regression model with robust error variance was used (total number of confirmed relapses as response variable; log-transformed treatment duration as "offset" variable; treatment group, region of enrolment and baseline EDSS stratum as covariates).

Outcome measures

Measure	Placebo n=253 Participants Placebo once daily	Teriflunomide 7 mg n=265 Participants Teriflunomide 7 mg once daily	Teriflunomide 14 mg n=233 Participants Teriflunomide 14 mg once daily
Extension Treatment Period: ARR: Poisson Regression Estimate	0.199 relapses per year Interval 0.156 to 0.254	0.200 relapses per year Interval 0.155 to 0.257	0.179 relapses per year Interval 0.132 to 0.243

OTHER_PRE_SPECIFIED outcome

Timeframe: From first study drug intake up to 112 days after last intake in the core treatment period or up to first intake in the extension treatment period, whichever occurred first

Population: All randomized and treated participants. Participants were considered according to the drug actually received. The 3 participants in the placebo group who received teriflunomide were analyzed according to the teriflunomide dose. The participant in the teriflunomide 14 mg group who received 7 mg was analyzed in the teriflunomide 7 mg group.

PCSA values are abnormal values considered medically important by the Sponsor according to predefined criteria based on literature review.

Hepatic parameters thresholds were defined as follows:

• Alanine Aminotransferase (ALT) >3, 5, 10 or 20 upper limit of normal(ULN);
• Aspartate aminotransferase (AST) >3, 5, 10 or 20 ULN;
• Alkaline Phosphatase >1.5 ULN;
• Total Bilirubin (TB) >1.5 or 2 ULN;
• ALT >3 ULN and TB >2 ULN.

Outcome measures

Measure	Placebo n=385 Participants Placebo once daily	Teriflunomide 7 mg n=409 Participants Teriflunomide 7 mg once daily	Teriflunomide 14 mg n=371 Participants Teriflunomide 14 mg once daily
Core Treatment Period: Liver Function: Number of Participants With Potentially Clinically Significant Abnormalities (PCSA) ALT >3 ULN	22 participants	31 participants	29 participants
Core Treatment Period: Liver Function: Number of Participants With Potentially Clinically Significant Abnormalities (PCSA) - ALT >5 ULN	14 participants	10 participants	11 participants
Core Treatment Period: Liver Function: Number of Participants With Potentially Clinically Significant Abnormalities (PCSA) - ALT >10 ULN	5 participants	2 participants	3 participants
Core Treatment Period: Liver Function: Number of Participants With Potentially Clinically Significant Abnormalities (PCSA) AST >3 ULN	13 participants	9 participants	9 participants
Core Treatment Period: Liver Function: Number of Participants With Potentially Clinically Significant Abnormalities (PCSA) - AST >5 ULN	9 participants	3 participants	3 participants
Core Treatment Period: Liver Function: Number of Participants With Potentially Clinically Significant Abnormalities (PCSA) Alkaline Phosphatase >1.5 ULN	5 participants	4 participants	2 participants
Core Treatment Period: Liver Function: Number of Participants With Potentially Clinically Significant Abnormalities (PCSA) TB >1.5 ULN	9 participants	6 participants	8 participants
Core Treatment Period: Liver Function: Number of Participants With Potentially Clinically Significant Abnormalities (PCSA) ALT >3 ULN and TB >2 ULN	2 participants	2 participants	0 participants

Adverse Events

Placebo

Serious events: 47 serious events

Other events: 247 other events

Deaths: 0 deaths

Teriflunomide 7 mg

Serious events: 52 serious events

Other events: 270 other events

Deaths: 0 deaths

Teriflunomide 14 mg

Serious events: 44 serious events

Other events: 254 other events

Deaths: 0 deaths

Placebo / 14 mg

Serious events: 16 serious events

Other events: 152 other events

Deaths: 0 deaths

Teriflunomide 7 mg / 14 mg

Serious events: 33 serious events

Other events: 153 other events

Deaths: 0 deaths

Teriflunomide 14 mg / 14 mg

Serious events: 29 serious events

Other events: 138 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=385 participants at risk Placebo once daily	Teriflunomide 7 mg n=409 participants at risk Teriflunomide 7 mg once daily	Teriflunomide 14 mg n=371 participants at risk Teriflunomide 14 mg once daily	Placebo / 14 mg n=251 participants at risk Core treatment period: Placebo once daily. Extension treatment period: Teriflunomide 14 mg once daily	Teriflunomide 7 mg / 14 mg n=267 participants at risk Core treatment period: Teriflunomide 7 mg once daily. Extension treatment period: Teriflunomide 14 mg once daily.	Teriflunomide 14 mg / 14 mg n=233 participants at risk Core treatment period: Teriflunomide 14 mg once daily. Extension treatment period: Teriflunomide 14 mg once daily.
Cardiac disorders Pericardial effusion	0.26% 1/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Infections and infestations Bronchitis	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.43% 1/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Infections and infestations Dengue fever	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.43% 1/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Infections and infestations Furuncle	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.43% 1/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Infections and infestations Gastroenteritis	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.24% 1/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.43% 1/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Infections and infestations Abscess jaw	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.40% 1/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Infections and infestations Abscess soft tissue	0.26% 1/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Infections and infestations Appendiceal abscess	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.27% 1/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Infections and infestations Appendicitis	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.24% 1/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.27% 1/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.40% 1/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Infections and infestations Bacterial sepsis	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.27% 1/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Infections and infestations Cellulitis	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.24% 1/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Infections and infestations Cytomegalovirus infection	0.26% 1/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Infections and infestations Diarrhoea infectious	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.27% 1/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Infections and infestations Endocarditis enterococcal	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.24% 1/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Infections and infestations Escherichia bacteraemia	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.24% 1/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Infections and infestations Hepatitis C	0.26% 1/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Infections and infestations Infected bites	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.24% 1/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Infections and infestations Influenza	0.26% 1/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Infections and infestations Lower respiratory tract infection	0.26% 1/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Infections and infestations Lung abscess	0.26% 1/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Infections and infestations Neuroborreliosis	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.27% 1/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Infections and infestations Osteomyelitis	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.27% 1/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Infections and infestations Paronychia	0.26% 1/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Infections and infestations Pelvic abscess	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.24% 1/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Infections and infestations Perichondritis	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.37% 1/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Infections and infestations Peritonitis	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.27% 1/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.37% 1/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Infections and infestations Pilonidal cyst	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.24% 1/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Infections and infestations Pneumonia	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.24% 1/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.75% 2/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Infections and infestations Pneumonia bacterial	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.27% 1/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Infections and infestations Post procedural infection	0.26% 1/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Infections and infestations Pulmonary tuberculosis	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.40% 1/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Infections and infestations Pyelonephritis	0.26% 1/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.27% 1/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Infections and infestations Pyelonephritis acute	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.24% 1/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Infections and infestations Respiratory tract infection	0.26% 1/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.24% 1/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Infections and infestations Salpingo-oophoritis	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.24% 1/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.37% 1/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Infections and infestations Sepsis	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.40% 1/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.37% 1/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Infections and infestations Septic shock	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.37% 1/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Infections and infestations Staphylococcal bacteraemia	0.26% 1/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Infections and infestations Staphylococcal infection	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.24% 1/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Infections and infestations Tonsillitis	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.27% 1/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Infections and infestations Tuberculosis gastrointestinal	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.27% 1/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Infections and infestations Urinary tract infection	0.52% 2/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.49% 2/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.54% 2/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.75% 2/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Infections and infestations Wound infection	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.24% 1/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.43% 1/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Papillary thyroid cancer	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.37% 1/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.43% 1/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Acoustic neuroma	0.26% 1/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Invasive ductal breast carcinoma	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.37% 1/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Invasive lobular breast carcinoma	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.40% 1/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lipoma	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.37% 1/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine leiomyoma	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.54% 2/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.37% 1/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Blood and lymphatic system disorders Microcytic anaemia	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.43% 1/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Blood and lymphatic system disorders Anaemia	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.24% 1/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.37% 1/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Blood and lymphatic system disorders Autoimmune thrombocytopenia	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.24% 1/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Blood and lymphatic system disorders Disseminated intravascular coagulation	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.27% 1/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Blood and lymphatic system disorders Lymphadenitis	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.24% 1/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Blood and lymphatic system disorders Neutropenia	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.49% 2/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.81% 3/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.27% 1/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.37% 1/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Immune system disorders Anaphylactic reaction	0.26% 1/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Endocrine disorders Adrenal insufficiency	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.37% 1/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Endocrine disorders Goitre	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.24% 1/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Metabolism and nutrition disorders Dehydration	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.27% 1/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.37% 1/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.43% 1/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Metabolism and nutrition disorders Diabetes mellitus	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.37% 1/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Metabolism and nutrition disorders Hyperamylasaemia	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.75% 2/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Metabolism and nutrition disorders Hyperlipasaemia	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.37% 1/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Metabolism and nutrition disorders Obesity	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.27% 1/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Metabolism and nutrition disorders Type 1 diabetes mellitus	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.24% 1/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Psychiatric disorders Completed suicide	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.27% 1/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.37% 1/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.43% 1/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Psychiatric disorders Suicide attempt	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.24% 1/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.81% 3/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.40% 1/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.43% 1/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Psychiatric disorders Anxiety	0.26% 1/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Psychiatric disorders Depression	0.26% 1/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.24% 1/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.27% 1/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.37% 1/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Psychiatric disorders Major depression	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.27% 1/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Psychiatric disorders Mental disorder	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.27% 1/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Psychiatric disorders Schizophrenia	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.24% 1/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Psychiatric disorders Suicidal behaviour	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.40% 1/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Psychiatric disorders Suicidal ideation	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.37% 1/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Nervous system disorders Cervicobrachial syndrome	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.43% 1/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Nervous system disorders Multiple sclerosis relapse	0.52% 2/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.24% 1/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.27% 1/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.40% 1/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.37% 1/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.43% 1/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Nervous system disorders Partial seizures	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.43% 1/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Nervous system disorders Sciatica	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.37% 1/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.43% 1/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Nervous system disorders Status epilepticus	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.43% 1/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Nervous system disorders Carpal tunnel syndrome	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.24% 1/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.27% 1/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Cardiac disorders Sinus bradycardia	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.40% 1/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Nervous system disorders Coma	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.40% 1/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Nervous system disorders Headache	0.78% 3/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.27% 1/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Nervous system disorders Hydrocephalus	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.40% 1/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Nervous system disorders Hypoaesthesia	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.27% 1/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Nervous system disorders Hypoglycaemic coma	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.37% 1/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Nervous system disorders Intracranial aneurysm	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.37% 1/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Nervous system disorders Intraventricular haemorrhage	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.40% 1/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Nervous system disorders Neuropathy peripheral	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.24% 1/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Nervous system disorders Polyneuropathy	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.27% 1/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Nervous system disorders Seizure	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.37% 1/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Nervous system disorders Somnolence	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.40% 1/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Nervous system disorders Subarachnoid haemorrhage	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.40% 1/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Nervous system disorders Syncope	0.26% 1/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.24% 1/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.27% 1/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.40% 1/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.37% 1/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Nervous system disorders Vertebrobasilar insufficiency	0.26% 1/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Ear and labyrinth disorders Tinnitus	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.24% 1/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Ear and labyrinth disorders Vertigo	0.26% 1/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.37% 1/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Cardiac disorders Atrioventricular block complete	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.43% 1/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Cardiac disorders Ventricular tachycardia	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.43% 1/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Cardiac disorders Atrial fibrillation	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.27% 1/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Cardiac disorders Coronary artery disease	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.40% 1/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Cardiac disorders Coronary artery occlusion	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.27% 1/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Cardiac disorders Myocardial infarction	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.24% 1/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Cardiac disorders Supraventricular tachycardia	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.27% 1/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Vascular disorders Blood pressure fluctuation	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.27% 1/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Vascular disorders Hypertension	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.27% 1/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Vascular disorders Shock haemorrhagic	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.27% 1/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Respiratory, thoracic and mediastinal disorders Lung disorder	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.43% 1/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Respiratory, thoracic and mediastinal disorders Asthma	0.52% 2/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.24% 1/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.27% 1/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Respiratory, thoracic and mediastinal disorders Atelectasis	0.26% 1/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.37% 1/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Respiratory, thoracic and mediastinal disorders Lung consolidation	0.26% 1/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.26% 1/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.27% 1/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.37% 1/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Respiratory, thoracic and mediastinal disorders Pulmonary hypertension	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.37% 1/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Gastrointestinal disorders Gastropleural fistula	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.43% 1/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Gastrointestinal disorders Haemorrhoids	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.37% 1/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.43% 1/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Gastrointestinal disorders Intestinal obstruction	0.26% 1/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.43% 1/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Gastrointestinal disorders Abdominal distension	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.37% 1/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Gastrointestinal disorders Abdominal pain	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.27% 1/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Gastrointestinal disorders Abdominal pain lower	0.26% 1/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.40% 1/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.40% 1/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Gastrointestinal disorders Colitis ulcerative	0.26% 1/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Gastrointestinal disorders Diarrhoea	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.27% 1/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Gastrointestinal disorders Dysphagia	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.37% 1/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Gastrointestinal disorders Enterocolitis	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.24% 1/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Gastrointestinal disorders Gastric ulcer	0.26% 1/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Gastrointestinal disorders Gastric ulcer haemorrhage	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.37% 1/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Gastrointestinal disorders Gastritis	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.24% 1/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Gastrointestinal disorders Haematemesis	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.37% 1/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Gastrointestinal disorders Haematochezia	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.24% 1/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Gastrointestinal disorders Inguinal hernia	0.26% 1/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Gastrointestinal disorders Pancreatitis	0.26% 1/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Gastrointestinal disorders Pancreatitis acute	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.37% 1/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.24% 1/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Gastrointestinal disorders Stress ulcer	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.24% 1/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Gastrointestinal disorders Vomiting	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.37% 1/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Hepatobiliary disorders Cholelithiasis	0.26% 1/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.27% 1/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.43% 1/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Hepatobiliary disorders Cholecystitis	0.78% 3/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.27% 1/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Hepatobiliary disorders Cholecystitis acute	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.27% 1/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Hepatobiliary disorders Cholecystitis chronic	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.40% 1/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Hepatobiliary disorders Gallbladder perforation	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.24% 1/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Hepatobiliary disorders Hepatic dysplasia	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.27% 1/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Hepatobiliary disorders Hepatitis toxic	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.27% 1/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Hepatobiliary disorders Jaundice cholestatic	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.24% 1/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Hepatobiliary disorders Liver injury	0.26% 1/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.24% 1/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Hepatobiliary disorders Non-alcoholic steatohepatitis	0.26% 1/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Skin and subcutaneous tissue disorders Angioedema	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.24% 1/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Musculoskeletal and connective tissue disorders Foot deformity	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.43% 1/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Musculoskeletal and connective tissue disorders Fracture nonunion	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.43% 1/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.43% 1/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Musculoskeletal and connective tissue disorders Knee deformity	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.43% 1/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Musculoskeletal and connective tissue disorders Back pain	0.26% 1/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.40% 1/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.37% 1/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Musculoskeletal and connective tissue disorders Muscle spasms	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.24% 1/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.24% 1/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.37% 1/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Renal and urinary disorders Acute kidney injury	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.75% 2/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Renal and urinary disorders Glomerulonephritis chronic	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.27% 1/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Renal and urinary disorders Renal artery stenosis	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.24% 1/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Renal and urinary disorders Renal cyst	0.26% 1/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Pregnancy, puerperium and perinatal conditions Ectopic pregnancy	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.43% 1/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Pregnancy, puerperium and perinatal conditions Pregnancy	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.24% 1/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Reproductive system and breast disorders Menorrhagia	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.24% 1/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.43% 1/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Reproductive system and breast disorders Benign prostatic hyperplasia	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.24% 1/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Reproductive system and breast disorders Cervical dysplasia	0.26% 1/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Reproductive system and breast disorders Menopausal symptoms	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.24% 1/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Reproductive system and breast disorders Ovarian cyst	0.26% 1/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Congenital, familial and genetic disorders Developmental hip dysplasia	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.43% 1/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Congenital, familial and genetic disorders Choledochal cyst	0.26% 1/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Congenital, familial and genetic disorders Congenital flat feet	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.24% 1/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
General disorders Asthenia	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.37% 1/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
General disorders General physical health deterioration	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.37% 1/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
General disorders Pain	0.26% 1/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
General disorders Pyrexia	0.26% 1/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.49% 2/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Investigations Alanine aminotransferase increased	1.6% 6/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	1.5% 6/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.81% 3/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.80% 2/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.37% 1/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.43% 1/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Investigations Amylase increased	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.43% 1/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Investigations Blood creatine phosphokinase increased	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	1.1% 3/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.43% 1/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Investigations Activated partial thromboplastin time prolonged	0.26% 1/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Investigations Aspartate aminotransferase increased	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.24% 1/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.27% 1/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.37% 1/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Investigations Gamma-glutamyltransferase increased	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.27% 1/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Investigations Hepatic enzyme increased	0.52% 2/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.37% 1/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Investigations Liver function test abnormal	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.24% 1/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.27% 1/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Investigations Neutrophil count decreased	0.26% 1/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Investigations Platelet count decreased	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.37% 1/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Investigations Transaminases increased	0.26% 1/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.27% 1/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.40% 1/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Investigations Weight decreased	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.40% 1/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.37% 1/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Injury, poisoning and procedural complications Intentional overdose	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.40% 1/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.43% 1/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Injury, poisoning and procedural complications Abdominal injury	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.27% 1/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Injury, poisoning and procedural complications Ankle fracture	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.27% 1/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Injury, poisoning and procedural complications Carbon monoxide poisoning	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.40% 1/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Injury, poisoning and procedural complications Contusion	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.24% 1/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Injury, poisoning and procedural complications Face injury	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.37% 1/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Injury, poisoning and procedural complications Fall	0.52% 2/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.49% 2/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Injury, poisoning and procedural complications Femoral neck fracture	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.24% 1/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Injury, poisoning and procedural complications Femur fracture	0.26% 1/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Injury, poisoning and procedural complications Foot fracture	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.40% 1/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Injury, poisoning and procedural complications Multiple fractures	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.24% 1/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Injury, poisoning and procedural complications Post procedural bile leak	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.24% 1/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Injury, poisoning and procedural complications Post procedural haemorrhage	0.26% 1/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Injury, poisoning and procedural complications Postoperative fever	0.26% 1/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Injury, poisoning and procedural complications Radius fracture	0.26% 1/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Injury, poisoning and procedural complications Road traffic accident	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.49% 2/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.37% 1/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Injury, poisoning and procedural complications Spinal compression fracture	0.26% 1/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Injury, poisoning and procedural complications Splenic rupture	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.24% 1/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Injury, poisoning and procedural complications Traumatic lung injury	0.00% 0/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.24% 1/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.

Other adverse events

Measure	Placebo n=385 participants at risk Placebo once daily	Teriflunomide 7 mg n=409 participants at risk Teriflunomide 7 mg once daily	Teriflunomide 14 mg n=371 participants at risk Teriflunomide 14 mg once daily	Placebo / 14 mg n=251 participants at risk Core treatment period: Placebo once daily. Extension treatment period: Teriflunomide 14 mg once daily	Teriflunomide 7 mg / 14 mg n=267 participants at risk Core treatment period: Teriflunomide 7 mg once daily. Extension treatment period: Teriflunomide 14 mg once daily.	Teriflunomide 14 mg / 14 mg n=233 participants at risk Core treatment period: Teriflunomide 14 mg once daily. Extension treatment period: Teriflunomide 14 mg once daily.
Infections and infestations Nasopharyngitis	16.9% 65/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	12.5% 51/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	11.9% 44/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	8.8% 22/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	7.9% 21/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	9.4% 22/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Infections and infestations Influenza	4.9% 19/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	5.4% 22/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	5.9% 22/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	3.2% 8/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	5.2% 14/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	6.9% 16/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Infections and infestations Urinary tract infection	9.4% 36/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	9.3% 38/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	7.0% 26/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	3.2% 8/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	4.5% 12/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	4.3% 10/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Infections and infestations Sinusitis	4.2% 16/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	6.1% 25/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	6.5% 24/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	2.0% 5/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	3.7% 10/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	3.9% 9/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Infections and infestations Upper respiratory tract infection	10.9% 42/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	8.6% 35/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	8.9% 33/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	4.4% 11/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	4.5% 12/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	3.0% 7/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Blood and lymphatic system disorders Neutropenia	2.6% 10/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	4.6% 19/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	4.9% 18/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.80% 2/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	4.9% 13/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	8.6% 20/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Psychiatric disorders Depression	6.5% 25/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	6.8% 28/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	4.9% 18/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	3.2% 8/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	5.6% 15/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	4.3% 10/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Nervous system disorders Headache	10.6% 41/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	14.9% 61/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	12.7% 47/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	4.0% 10/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	5.6% 15/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	7.3% 17/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Nervous system disorders Hypoaesthesia	4.2% 16/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	5.4% 22/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	6.2% 23/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	4.8% 12/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	2.2% 6/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	3.4% 8/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Nervous system disorders Dizziness	6.0% 23/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	4.2% 17/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	6.7% 25/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	1.2% 3/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	3.0% 8/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	1.7% 4/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Nervous system disorders Paraesthesia	6.0% 23/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	6.6% 27/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	5.9% 22/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	4.8% 12/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	1.9% 5/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	1.7% 4/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Vascular disorders Hypertension	2.1% 8/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	4.2% 17/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	4.3% 16/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	4.0% 10/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	4.9% 13/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	5.2% 12/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Respiratory, thoracic and mediastinal disorders Cough	3.1% 12/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	5.1% 21/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	3.2% 12/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	2.0% 5/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	2.2% 6/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	1.3% 3/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Gastrointestinal disorders Diarrhoea	10.1% 39/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	11.0% 45/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	9.4% 35/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	5.6% 14/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	6.7% 18/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	8.6% 20/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Gastrointestinal disorders Nausea	7.0% 27/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	9.3% 38/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	9.7% 36/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	5.6% 14/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	3.7% 10/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	3.4% 8/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Skin and subcutaneous tissue disorders Alopecia	4.2% 16/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	10.3% 42/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	13.5% 50/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	14.3% 36/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	2.2% 6/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	2.1% 5/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Musculoskeletal and connective tissue disorders Back pain	7.8% 30/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	6.8% 28/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	8.6% 32/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	4.8% 12/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	4.9% 13/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	5.6% 13/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Musculoskeletal and connective tissue disorders Arthralgia	3.9% 15/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	7.3% 30/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	5.4% 20/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	2.8% 7/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	3.4% 9/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	3.9% 9/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Musculoskeletal and connective tissue disorders Pain in extremity	5.5% 21/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	4.6% 19/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	6.7% 25/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	2.8% 7/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	3.4% 9/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	3.9% 9/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
General disorders Fatigue	10.4% 40/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	8.1% 33/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	10.0% 37/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	3.6% 9/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	4.5% 12/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	2.6% 6/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Investigations Alanine aminotransferase increased	7.0% 27/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	10.5% 43/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	12.9% 48/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	10.8% 27/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	3.0% 8/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	3.9% 9/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Injury, poisoning and procedural complications Fall	3.6% 14/385 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	5.4% 22/409 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	6.2% 23/371 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	1.6% 4/251 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	2.6% 7/267 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	3.0% 7/233 • AEs were collected from signature of the Informed Consent Form up to the last visit (174 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened and death that occurred during first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.

Additional Information

Trial Transparency Team

Sanofi

Email: Contact-US@sanofi.com

Results disclosure agreements

• Principal investigator is a sponsor employee If no publication has occurred within 12 months after trial completion, the Investigator can present or publish results. The investigator provides the sponsor with a copy of the presentation or publication for review and comment at least 30 days in advance of its submission. The sponsor can delay the submission for a period not exceeding 90 days to allow for filing a patent application or such other measures as sponsor deems appropriate to establish and preserve its proprietary rights.
• Publication restrictions are in place

Restriction type: OTHER