Trial Outcomes & Findings for A Study Comparing the Effectiveness and Safety of Teriflunomide and Interferon Beta-1a in Patients With Relapsing Multiple Sclerosis (NCT NCT00883337)

NCT ID: NCT00883337

Last Updated: 2016-06-13

Results Overview

Failure was defined as the first occurence of confirmed relapse or permanent treatment discontinuation (for any cause) which ever came first. If no events occurred, the participant was considered free of failure. 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.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 324 participants
• Primary outcome timeframe: Core treatment period between 48 and 118 weeks depending on when the participant was enrolled
• Results posted on: 2016-06-13

Participant Flow

The recruitment initiated in April 2009 was completed in July 2010. A total of 369 participants were screened at 54 sites in 13 countries. The common end date of core treatment period was 14 September 2011 (maximum treatment duration of 115 weeks). The end date of extension was 13 May 2015 (maximum treatment duration of 197 weeks)

Randomization was stratified by country and baseline disability (Expanded Disability Status Scale [EDSS] score ≤3.5 or >3.5). Assignment to groups was done centrally using an Interactive Voice Response System (IVRS] in a 1:1:1 ratio after confirmation of the selection criteria. 324 participants were randomized at 53 sites.

Participant milestones

Measure	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.	IFN-β-1a / Teriflunomide 14 mg Core treatment period: Interferon β-1a 3 times a week. Extension treatment period: Teriflunomide 14 mg once daily.
Core Treatment Period STARTED	109	111	104
Core Treatment Period Treated	109	111	101
Core Treatment Period COMPLETED	89	89	71
Core Treatment Period NOT COMPLETED	20	22	33
Extension Treatment Period STARTED	89	89	59
Extension Treatment Period COMPLETED	61	66	40
Extension Treatment Period NOT COMPLETED	28	23	19

Reasons for withdrawal

Measure	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.	IFN-β-1a / Teriflunomide 14 mg Core treatment period: Interferon β-1a 3 times a week. Extension treatment period: Teriflunomide 14 mg once daily.
Core Treatment Period Adverse Event	9	12	22
Core Treatment Period Lack of Efficacy	7	4	2
Core Treatment Period Lost to Follow-up	1	1	0
Core Treatment Period Withdrawal by Subject	2	2	6
Core Treatment Period Wish to be pregnant	1	2	1
Core Treatment Period Poor compliance to protocol	0	0	1
Core Treatment Period Other than above	0	1	1
Extension Treatment Period Adverse Event	8	5	5
Extension Treatment Period Lack of Efficacy	8	8	8
Extension Treatment Period Poor compliance to protocol	1	1	1
Extension Treatment Period Lost to Follow-up	1	0	0
Extension Treatment Period Other than above	10	9	5

Baseline Characteristics

A Study Comparing the Effectiveness and Safety of Teriflunomide and Interferon Beta-1a in Patients With Relapsing Multiple Sclerosis

Baseline characteristics by cohort

Measure	Teriflunomide 7 mg / 14 mg n=109 Participants Core treatment period: Teriflunomide 7 mg once daily Extension treatment period: Teriflunomide 14 mg once daily	Teriflunomide 14 mg/14 mg n=111 Participants Core treatment period: Teriflunomide 14 mg once daily. Extension treatment period: Teriflunomide 14 mg once daily.	IFNβ1a / Teriflunomide 14 mg n=104 Participants Core treatment period: Interferon β-1a 3 times a week. Extension treatment period: Teriflunomide 14 mg once daily.	Total n=324 Participants Total of all reporting groups
Age, Continuous	32.5 years STANDARD_DEVIATION 9.2 • n=93 Participants	36.8 years STANDARD_DEVIATION 10.3 • n=4 Participants	37.0 years STANDARD_DEVIATION 10.6 • n=27 Participants	36.3 years STANDARD_DEVIATION 10.0 • n=483 Participants
Sex: Female, Male Female	70 Participants n=93 Participants	78 Participants n=4 Participants	71 Participants n=27 Participants	219 Participants n=483 Participants
Sex: Female, Male Male	39 Participants n=93 Participants	33 Participants n=4 Participants	33 Participants n=27 Participants	105 Participants n=483 Participants
Region of enrollment North America	8 participants n=93 Participants	6 participants n=4 Participants	7 participants n=27 Participants	21 participants n=483 Participants
Region of enrollment Eastern Europe	39 participants n=93 Participants	41 participants n=4 Participants	35 participants n=27 Participants	115 participants n=483 Participants
Region of enrollment Western Europe*	62 participants n=93 Participants	64 participants n=4 Participants	62 participants n=27 Participants	188 participants n=483 Participants
Time since first diagnosis of Multiple Sclerosis [MS]	3.72 years STANDARD_DEVIATION 5.19 • n=93 Participants	3.68 years STANDARD_DEVIATION 6.24 • n=4 Participants	3.82 years STANDARD_DEVIATION 5.69 • n=27 Participants	3.74 years STANDARD_DEVIATION 5.71 • n=483 Participants
Number of MS relapses Within the past year	1 relapses n=93 Participants	1 relapses n=4 Participants	1 relapses n=27 Participants	1 relapses n=483 Participants
Number of MS relapses Within the past 2 years	2 relapses n=93 Participants	2 relapses n=4 Participants	2 relapses n=27 Participants	2 relapses n=483 Participants
Time since most recent MS relapse onset	9.00 months STANDARD_DEVIATION 13.96 • n=93 Participants	7.90 months STANDARD_DEVIATION 10.34 • n=4 Participants	9.79 months STANDARD_DEVIATION 10.72 • n=27 Participants	8.88 months STANDARD_DEVIATION 11.79 • n=483 Participants
MS subtype Relapsing Remitting	109 participants n=93 Participants	108 participants n=4 Participants	104 participants n=27 Participants	321 participants n=483 Participants
MS subtype Secondary Progressive	0 participants n=93 Participants	1 participants n=4 Participants	0 participants n=27 Participants	1 participants n=483 Participants
MS subtype Progressive Relapsing	0 participants n=93 Participants	2 participants n=4 Participants	0 participants n=27 Participants	2 participants n=483 Participants
Baseline EDSS score ≤3.5	96 participants n=93 Participants	95 participants n=4 Participants	93 participants n=27 Participants	284 participants n=483 Participants
Baseline EDSS score >3.5	13 participants n=93 Participants	16 participants n=4 Participants	11 participants n=27 Participants	40 participants n=483 Participants

PRIMARY outcome

Timeframe: Core treatment period between 48 and 118 weeks depending on when the participant was enrolled

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

Failure was defined as the first occurence of confirmed relapse or permanent treatment discontinuation (for any cause) which ever came first. If no events occurred, the participant was considered free of failure.

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.

Outcome measures

Measure	Teriflunomide 7 mg n=109 Participants Teriflunomide 7 mg once daily	Teriflunomide 14 mg n=111 Participants Teriflunomide 14 mg once daily	IFN-β-1a n=104 Participants Interferon β-1a 3 times a week
Core Treatment Period: Overview of Failures Failure	53 participants	42 participants	44 participants
Core Treatment Period: Overview of Failures Free of failure	56 participants	69 participants	60 participants

PRIMARY outcome

Timeframe: Core treatment period between 48 and 118 weeks depending on when the participant was enrolled

Population: ITT population.

Probability of disability progression at 24, 48 and 96 weeks was estimated using Kaplan-Meier method on the time to failure defined as the time from randomization to failure. Participants free of failure were censored at the date of last treatment.

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	Teriflunomide 7 mg n=109 Participants Teriflunomide 7 mg once daily	Teriflunomide 14 mg n=111 Participants Teriflunomide 14 mg once daily	IFN-β-1a n=104 Participants Interferon β-1a 3 times a week
Core Treatment Period: Time to Failure: Kaplan-Meier Estimates of the Rate of Failure at Timepoints Probability of failure at 24 weeks	25.7 percent probability Interval 17.5 to 33.9	24.3 percent probability Interval 16.3 to 32.3	29.8 percent probability Interval 21.0 to 38.6
Core Treatment Period: Time to Failure: Kaplan-Meier Estimates of the Rate of Failure at Timepoints Probability of failure at 48 weeks	35.8 percent probability Interval 26.8 to 44.8	33.3 percent probability Interval 24.6 to 42.1	36.5 percent probability Interval 27.3 to 45.8
Core Treatment Period: Time to Failure: Kaplan-Meier Estimates of the Rate of Failure at Timepoints Probability of failure at 96 weeks	58.8 percent probability Interval 46.1 to 71.4	41.1 percent probability Interval 30.9 to 51.4	44.4 percent probability Interval 34.3 to 54.4

SECONDARY outcome

Timeframe: Core treatment period between 48 and 118 weeks depending on when the participant was enrolled

Population: ITT population.

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

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	Teriflunomide 7 mg n=109 Participants Teriflunomide 7 mg once daily	Teriflunomide 14 mg n=111 Participants Teriflunomide 14 mg once daily	IFN-β-1a n=104 Participants Interferon β-1a 3 times a week
Core Treatment Period: Annualized Relapse Rate [ARR] - Poisson Regression Estimates	0.410 relapses per year Interval 0.265 to 0.636	0.259 relapses per year Interval 0.153 to 0.438	0.216 relapses per year Interval 0.113 to 0.415

SECONDARY outcome

Timeframe: Baseline (before randomization) and 48 weeks

Population: ITT population.

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

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

Least-square means 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).

Outcome measures

Measure	Teriflunomide 7 mg n=109 Participants Teriflunomide 7 mg once daily	Teriflunomide 14 mg n=111 Participants Teriflunomide 14 mg once daily	IFN-β-1a n=104 Participants Interferon β-1a 3 times a week
Core Treatment Period: Change From Baseline in Fatigue Impact Scale (FIS) Total Score	0.97 units on a scale Standard Error 2.96	4.10 units on a scale Standard Error 3.03	9.10 units on a scale Standard Error 3.21

SECONDARY outcome

Timeframe: 48 weeks

Population: ITT population.

TSQM version 1.4 is an instrument to assess patients' satisfaction with medication. It consists of 13 questions that cover three dimensions (effectiveness, side effects and convenience) plus a global satisfaction question. Four scores ranging from 0 to 100 (extremely satisfied) are obtained. Least-square means were estimated using a Mixed-effect model with repeated measures [MMRM] on TSQM score data (treatment group, region of enrollment, baseline EDSS stratum, visit, treatment-by-visit interaction as factors).

Outcome measures

Measure	Teriflunomide 7 mg n=109 Participants Teriflunomide 7 mg once daily	Teriflunomide 14 mg n=111 Participants Teriflunomide 14 mg once daily	IFN-β-1a n=104 Participants Interferon β-1a 3 times a week
Core Treatment Period: Treatment Satisfaction Questionnaire for Medication [TSQM] Scores Effectivness score	67.25 units on a scale Standard Error 2.70	63.13 units on a scale Standard Error 2.75	59.30 units on a scale Standard Error 2.97
Core Treatment Period: Treatment Satisfaction Questionnaire for Medication [TSQM] Scores Side effects score	95.29 units on a scale Standard Error 2.31	93.15 units on a scale Standard Error 2.34	71.38 units on a scale Standard Error 2.50
Core Treatment Period: Treatment Satisfaction Questionnaire for Medication [TSQM] Scores Convenience score	88.30 units on a scale Standard Error 1.97	89.85 units on a scale Standard Error 1.98	61.90 units on a scale Standard Error 2.11
Core Treatment Period: Treatment Satisfaction Questionnaire for Medication [TSQM] Scores Global satisfaction score	68.29 units on a scale Standard Error 2.77	68.82 units on a scale Standard Error 2.78	60.98 units on a scale Standard Error 2.94

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: Safety population: all randomized and treated participants. Participants were considered according to the drug actually received. The participant randomized to Teriflunomide 14 mg group who received Teriflunomide 7 mg was analyzed in the Teriflunomide 7 mg group.

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	Teriflunomide 7 mg n=110 Participants Teriflunomide 7 mg once daily	Teriflunomide 14 mg n=110 Participants Teriflunomide 14 mg once daily	IFN-β-1a n=101 Participants Interferon β-1a 3 times a week
Core Treatment Period: Overview of Adverse Events [AE] - Any AE leading to death	0 participants	0 participants	0 participants
Core Treatment Period: Overview of Adverse Events [AE] - Any AE leading to treatment discontinuation	9 participants	12 participants	22 participants
Core Treatment Period: Overview of Adverse Events [AE] Any AE	103 participants	102 participants	97 participants
Core Treatment Period: Overview of Adverse Events [AE] - Any serious AE	12 participants	6 participants	7 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. Participants were considered in the treatment group to which they were randomized regardless of the drug they actually received.

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	Teriflunomide 7 mg n=90 Participants Teriflunomide 7 mg once daily	Teriflunomide 14 mg n=88 Participants Teriflunomide 14 mg once daily	IFN-β-1a n=59 Participants Interferon β-1a 3 times a week
Extension Treatment Period: Overview of AEs Any AE	83 participants	76 participants	48 participants
Extension Treatment Period: Overview of AEs Any serious AE	9 participants	13 participants	12 participants
Extension Treatment Period: Overview of AEs Any AE leading to death	0 participants	0 participants	0 participants
Extension Treatment Period: Overview of AEs Any AE leading to treatment discontinuation	8 participants	6 participants	5 participants

SECONDARY outcome

Timeframe: Extension treatment period (Maximum: 197 weeks)

Population: ITT population.

ARR was obtained from the total number of confirmed relapses that occurred during the treatment period divided by the sum of the standardized treatment durations.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	Teriflunomide 7 mg n=89 Participants Teriflunomide 7 mg once daily	Teriflunomide 14 mg n=89 Participants Teriflunomide 14 mg once daily	IFN-β-1a n=59 Participants Interferon β-1a 3 times a week
Extension Treatment Period: ARR Poisson Regression Estimates	0.236 relapses per year Interval 0.154 to 0.362	0.193 relapses per year Interval 0.121 to 0.307	0.252 relapses per year Interval 0.145 to 0.438

Adverse Events

Core Treatment Period: Teriflunomide 7 mg

Serious events: 12 serious events

Other events: 85 other events

Deaths: 0 deaths

Core Treatment:Teriflunomide 14 mg

Serious events: 6 serious events

Other events: 92 other events

Deaths: 0 deaths

Core Treatment: IFN-β-1a

Serious events: 7 serious events

Other events: 92 other events

Deaths: 0 deaths

Extended Treatment: Teriflunomide 14 mg (After 7 mg)

Serious events: 9 serious events

Other events: 72 other events

Deaths: 0 deaths

Extended Treatment: Teriflunomide 14 mg (After 14 mg)

Serious events: 13 serious events

Other events: 65 other events

Deaths: 0 deaths

Extended Treatment: Teriflunomide 14 mg (After IFN-β-1a)

Serious events: 12 serious events

Other events: 48 other events

Deaths: 0 deaths

Serious adverse events

Measure	Core Treatment Period: Teriflunomide 7 mg n=110 participants at risk Teriflunomide 7 mg once daily (mean exposure of 456.62 days).	Core Treatment:Teriflunomide 14 mg n=110 participants at risk Teriflunomide 14 mg once daily (mean exposure of 434.43 days).	Core Treatment: IFN-β-1a n=101 participants at risk Interferon β-1a 3 times a week (mean exposure of 405.18 days).	Extended Treatment: Teriflunomide 14 mg (After 7 mg) n=90 participants at risk Teriflunomide 14 mg once daily in extended treatment period after 7 mg in the core treatment period (mean exposure of 996.76 days).	Extended Treatment: Teriflunomide 14 mg (After 14 mg) n=88 participants at risk Teriflunomide 14 mg once daily in extended treatment period after 14 mg in core treatment period (mean exposure of 1015.32 days).	Extended Treatment: Teriflunomide 14 mg (After IFN-β-1a) n=59 participants at risk Teriflunomide 14 mg once daily in extended treatment period after Interferon β-1a 3 times a week in core treatment period (mean exposure of 1000.03 days).
Nervous system disorders Trigeminal neuralgia	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 1/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Eye disorders Eye oedema	0.91% 1/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.
Eye disorders Optic ischaemic neuropathy	0.91% 1/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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 perforated	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 1/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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 pyelonephritis	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 1/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 1/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 1/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.91% 1/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 1/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 1/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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 Anal abscess	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.99% 1/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 1/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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 infection	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 1/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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	0.91% 1/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 1/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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 Cervicitis	0.91% 1/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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 Chronic sinusitis	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.91% 1/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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 Meningitis bacterial	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 1/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 1/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 1/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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 Urosepsis	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 1/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 1/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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 leiomyosarcoma	0.91% 1/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 1/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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 Haemolysis	0.91% 1/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.91% 1/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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 Drug hypersensitivity	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 1/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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 Hyperkalaemia	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 1/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 1/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 1/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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 Hypomania	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 1/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 1/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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 Haemorrhagic stroke	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 1/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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 Optic neuritis	0.91% 1/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 1/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 1/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 1/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.91% 1/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 1/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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 Pericarditis	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 1/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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 tachycardia	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 1/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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	0.91% 1/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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 Varicose vein	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 1/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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 Deep vein thrombosis	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 1/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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 Haematoma	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 1/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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 Venous stenosis	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.99% 1/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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 Nasal septum deviation	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 1/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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 Duodenal perforation	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 1/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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 Crohn's disease	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 1/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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	0.91% 1/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 1/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.99% 1/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 1/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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 Erythema nodosum	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 1/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 1/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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 disorder	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.99% 1/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 1/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.91% 1/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 1/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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 Spinal osteoarthritis	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 1/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 1/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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 Nephrolithiasis	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 1/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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 Abortion spontaneous	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 1/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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 Uterine haemorrhage	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 1/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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 polyp	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.99% 1/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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 Gait disturbance	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 1/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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	2.7% 3/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.91% 1/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.99% 1/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 2/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 1/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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 Forearm fracture	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.99% 1/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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 Tibia fracture	0.91% 1/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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	Core Treatment Period: Teriflunomide 7 mg n=110 participants at risk Teriflunomide 7 mg once daily (mean exposure of 456.62 days).	Core Treatment:Teriflunomide 14 mg n=110 participants at risk Teriflunomide 14 mg once daily (mean exposure of 434.43 days).	Core Treatment: IFN-β-1a n=101 participants at risk Interferon β-1a 3 times a week (mean exposure of 405.18 days).	Extended Treatment: Teriflunomide 14 mg (After 7 mg) n=90 participants at risk Teriflunomide 14 mg once daily in extended treatment period after 7 mg in the core treatment period (mean exposure of 996.76 days).	Extended Treatment: Teriflunomide 14 mg (After 14 mg) n=88 participants at risk Teriflunomide 14 mg once daily in extended treatment period after 14 mg in core treatment period (mean exposure of 1015.32 days).	Extended Treatment: Teriflunomide 14 mg (After IFN-β-1a) n=59 participants at risk Teriflunomide 14 mg once daily in extended treatment period after Interferon β-1a 3 times a week in core treatment period (mean exposure of 1000.03 days).
Infections and infestations Nasopharyngitis	23.6% 26/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	21.8% 24/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	16.8% 17/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	12.2% 11/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	10.2% 9/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 3/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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	7.3% 8/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	2.7% 3/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 6/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 8/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	8.0% 7/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 3/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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	7.3% 8/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 4/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 2/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 4/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	5.7% 5/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 4/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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	7.3% 8/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 11/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 9/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 2/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	5.7% 5/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 3/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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 Oral herpes	8.2% 9/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 2/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 1/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 4/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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 Pharyngitis	7.3% 8/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.91% 1/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 3/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 4/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 4/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	8.5% 5/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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	7.3% 8/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	8.2% 9/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	5.0% 5/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	3.3% 3/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	2.3% 2/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 2/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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 Ear infection	2.7% 3/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	1.8% 2/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 2/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 1/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 3/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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	4.5% 5/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	5.5% 6/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 3/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	7.8% 7/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 1/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 1/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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	0.91% 1/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	1.8% 2/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 4/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 1/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	2.3% 2/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 3/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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 Insomnia	6.4% 7/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.91% 1/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	5.0% 5/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 2/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 1/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 2/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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	5.5% 6/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	2.7% 3/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 2/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	3.3% 3/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 4/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 3/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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	3.6% 4/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.91% 1/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 6/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	3.3% 3/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 3/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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	20.9% 23/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	15.5% 17/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	25.7% 26/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 5/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 3/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	16.9% 10/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 3/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 1/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 3/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 3/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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	12.7% 14/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 11/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 8/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	3.3% 3/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	2.3% 2/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 3/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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	0.91% 1/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.91% 1/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 2/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 5/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 6/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	8.5% 5/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 5/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 4/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	7.8% 7/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	10.2% 9/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 7/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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	6.4% 7/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 4/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.99% 1/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 4/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	2.3% 2/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	8.5% 5/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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	17.3% 19/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	15.5% 17/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 9/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	11.1% 10/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	17.0% 15/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	13.6% 8/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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	4.5% 5/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	6.4% 7/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 2/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 6/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 3/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 2/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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	6.4% 7/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	6.4% 7/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 3/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	3.3% 3/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 3/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 4/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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	9.1% 10/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	9.1% 10/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 4/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	2.3% 2/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 1/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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 Dyspepsia	3.6% 4/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 4/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	3.3% 3/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 1/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 3/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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	5.5% 6/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	8.2% 9/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 4/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 2/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 1/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 1/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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	5.5% 6/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	20.0% 22/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.99% 1/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 4/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 1/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 4/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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	9.1% 10/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 11/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 7/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 5/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 6/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	8.5% 5/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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	10.0% 11/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	6.4% 7/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 4/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 6/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 4/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 4/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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	5.5% 6/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	6.4% 7/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 4/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 6/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 3/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 4/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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	5.5% 6/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 5/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 3/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 1/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	2.3% 2/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 2/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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 Myalgia	1.8% 2/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	2.7% 3/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 7/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 2/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 1/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 1/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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 Micturition urgency	1.8% 2/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	2.7% 3/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.99% 1/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 2/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	2.3% 2/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 3/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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 Dysmenorrhoea	2.7% 3/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	5.5% 6/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.99% 1/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 1/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	2.3% 2/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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	6.4% 7/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	5.5% 6/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	5.0% 5/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 4/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 4/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 2/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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	2.7% 3/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.91% 1/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 9/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	2.3% 2/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 3/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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	9.1% 10/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	1.8% 2/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 3/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 1/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 1/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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 Influenza like illness	3.6% 4/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 4/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	48.5% 49/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 2/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	10.2% 6/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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 Injection site erythema	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	9.9% 10/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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	10.9% 12/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	8.2% 9/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	29.7% 30/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 5/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	9.1% 8/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 2/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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	5.5% 6/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	1.8% 2/110 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 2/101 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	3.3% 3/90 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from first intake of study drug in extension treatment period up to 28 days after the last intake in the extension study treatment period.	0.00% 0/88 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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% 1/59 • AEs were collected from signature of the Informed Consent Form up to the last visit (197 weeks) in the study. The analysis was performed on the safety population as previously defined and included all AE that developed or worsened from 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