Trial Outcomes & Findings for Long-term Safety and Tolerability of 0.5 mg Fingolimod in Patients With Relapsing Forms of Multiple Sclerosis (NCT NCT01201356)

NCT ID: NCT01201356

Last Updated: 2021-04-21

Results Overview

Analysis of absolute and relative frequencies for Adverse Event (AE), Serious Adverse Event (SAE) and Deaths by primary System Organ Class (SOC) to demonstrate that Fingolimod 0.5 mg/day is safe in patients with relapsing forms of Multiple Sclerosis (MS) through the monitoring of relevant clinical and laboratory safety parameters. Only descriptive analysis performed.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

4125 participants

Primary outcome timeframe

Baseline (Part I) to Month 6 Follow-up (Part II), up to 8 years

Results posted on

2021-04-21

Participant Flow

This was an open-label, multi-center, single treatment arm design allowing patients participating in the fingolimod MS clinical development program to enroll in order to collect additional long-term safety, tolerability, efficacy, and health outcomes data.

This study had two parts: Part 1, collecting long-term safety, tolerability, efficacy and health outcomes data until all Part 1 end of study (EOS) visits and last follow-up visit; Part 2, collecting limited safety and tolerability data, in a subset of patients who participated in Part 1, and other eligible patients from ongoing fingolimod trials.

Participant milestones

Participant milestones
Measure	Fingolimod 0.5 mg/Day Open-label fingolimod 0.5 mg, taken orally once daily
Overall Study STARTED	4125
Overall Study Safety Set	4083
Overall Study Fingolimod Full Analysis Set	4046
Overall Study COMPLETED	3481
Overall Study NOT COMPLETED	644

Reasons for withdrawal

Reasons for withdrawal
Measure	Fingolimod 0.5 mg/Day Open-label fingolimod 0.5 mg, taken orally once daily
Overall Study Adverse Event	170
Overall Study Abnormal laboratory value(s)	51
Overall Study Abnormal test procedure result(s)	3
Overall Study Unsatisfactory therapeutic effect	112
Overall Study Condition no longer requires study drug	12
Overall Study Withdrawal by Subject	144
Overall Study Lost to Follow-up	50
Overall Study administrative problems	74
Overall Study Death	16
Overall Study Protocol Violation	12

Baseline Characteristics

Long-term Safety and Tolerability of 0.5 mg Fingolimod in Patients With Relapsing Forms of Multiple Sclerosis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Fingolimod 0.5 mg/Day n=4125 Participants Open-label fingolimod 0.5 mg, taken orally once daily
Age, Continuous	37.8 years STANDARD_DEVIATION 9.05 • n=5 Participants
Age, Customized < 18 years	1 Participants n=5 Participants
Age, Customized 18 - 30 years	951 Participants n=5 Participants
Age, Customized 31 - 40 years	1497 Participants n=5 Participants
Age, Customized 41 - 55 years	1605 Participants n=5 Participants
Age, Customized > 55 years	71 Participants n=5 Participants
Sex: Female, Male Female	2933 Participants n=5 Participants
Sex: Female, Male Male	1192 Participants n=5 Participants
Race/Ethnicity, Customized Caucasian	3927 Participants n=5 Participants
Race/Ethnicity, Customized Black	38 Participants n=5 Participants
Race/Ethnicity, Customized Asian	35 Participants n=5 Participants
Race/Ethnicity, Customized Native American	11 Participants n=5 Participants
Race/Ethnicity, Customized Other	114 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline (Part I) to Month 6 Follow-up (Part II), up to 8 years

Population: Safety Set

Outcome measures

Outcome measures
Measure	Fingolimod 0.5 mg/Day n=4083 Participants Open-label fingolimod 0.5 mg, taken orally once daily
Parts I and II: Number of Participants With Adverse Events, Serious Adverse Event, and Death Adverse Event (AEs)	2125 Participants
Parts I and II: Number of Participants With Adverse Events, Serious Adverse Event, and Death Serious Adverse Events (SAEs)	515 Participants
Parts I and II: Number of Participants With Adverse Events, Serious Adverse Event, and Death Deaths	16 Participants

SECONDARY outcome

Timeframe: Month 0 (Core Baseline) to End of Follow-up Visit (an average of 162 months)

Population: Fingolimod full analysis set. Only participants with an observed value were considered for the analysis.

Annualized relapse rate (ARR) is defined as the number of all relapses (including both confirmed and unconfirmed relapses) experienced during a specific period of time adjusted to a one-year period. ARR is calculated as follows: (total number of all relapses) / (total number of days in the study for all patients for that specific period of time) x 365.25. Month 0 is the first dose of fingolimod study drug among all studies in which patient participated. Only descriptive analysis performed.

Outcome measures

Outcome measures
Measure	Fingolimod 0.5 mg/Day n=4046 Participants Open-label fingolimod 0.5 mg, taken orally once daily
Part I: Aggregate Annualized Relapse Rates (ARR) From First Dose of Fingolimod Month 0 to Month 156	0.169 Annual number of relapses per patient
Part I: Aggregate Annualized Relapse Rates (ARR) From First Dose of Fingolimod Month 0 to Month 6	0.325 Annual number of relapses per patient
Part I: Aggregate Annualized Relapse Rates (ARR) From First Dose of Fingolimod Month 0 to Month 12	0.273 Annual number of relapses per patient
Part I: Aggregate Annualized Relapse Rates (ARR) From First Dose of Fingolimod Month 0 to Month 24	0.237 Annual number of relapses per patient
Part I: Aggregate Annualized Relapse Rates (ARR) From First Dose of Fingolimod Month 0 to Month 36	0.217 Annual number of relapses per patient
Part I: Aggregate Annualized Relapse Rates (ARR) From First Dose of Fingolimod Month 0 to Month 48	0.208 Annual number of relapses per patient
Part I: Aggregate Annualized Relapse Rates (ARR) From First Dose of Fingolimod Month 0 to Month 60	0.197 Annual number of relapses per patient
Part I: Aggregate Annualized Relapse Rates (ARR) From First Dose of Fingolimod Month 0 to Month 72	0.190 Annual number of relapses per patient
Part I: Aggregate Annualized Relapse Rates (ARR) From First Dose of Fingolimod Month 0 to Month 84	0.182 Annual number of relapses per patient
Part I: Aggregate Annualized Relapse Rates (ARR) From First Dose of Fingolimod Month 0 to Month 96	0.177 Annual number of relapses per patient
Part I: Aggregate Annualized Relapse Rates (ARR) From First Dose of Fingolimod Month 0 to Month 108	0.172 Annual number of relapses per patient
Part I: Aggregate Annualized Relapse Rates (ARR) From First Dose of Fingolimod Month 0 to Month 120	0.170 Annual number of relapses per patient
Part I: Aggregate Annualized Relapse Rates (ARR) From First Dose of Fingolimod Month 0 to Month 132	0.170 Annual number of relapses per patient
Part I: Aggregate Annualized Relapse Rates (ARR) From First Dose of Fingolimod Month 0 to Month 144	0.169 Annual number of relapses per patient
Part I: Aggregate Annualized Relapse Rates (ARR) From First Dose of Fingolimod Month 0 to end of Study	0.166 Annual number of relapses per patient
Part I: Aggregate Annualized Relapse Rates (ARR) From First Dose of Fingolimod Month 0 to end of Follow-up	0.169 Annual number of relapses per patient

SECONDARY outcome

Timeframe: Month 0 (Core Baseline) to End of Follow-up Visit (an average of 162 months)

Population: Fingolimod full analysis set. Only participants with an observed value were considered for the analysis.

A relapse is defined as the appearance of a new neurological abnormality or worsening of previously stable or improving pre-existing neurological abnormality, separated by at least 30 days from onset of a preceding clinical demyelinating event. The abnormality must be present for at least 24 hours and occur in the absence of fever (\<37.5°C) or infection. In Study Part One, a relapse must be confirmed by an Expanded Disability Status Scale (EDSS) certified Physician within 7 days of the onset of symptoms. A relapse is confirmed when it is accompanied by an increase of at least half a step (0.5) on the EDSS or an increase of 1 point on two different Functional Systems (FS) of the EDSS or 2 points on one of the FS (excluding Bowel/Bladder or Cerebral FS). Month 0 is the first dose of fingolimod study drug among all studies in which patient participated. Only descriptive analysis performed.

Outcome measures

Outcome measures
Measure	Fingolimod 0.5 mg/Day n=4046 Participants Open-label fingolimod 0.5 mg, taken orally once daily
Part I: Number of Participants With Relapses (Confirmed and Unconfirmed) From First Dose of Fingolimod Month 0 to Month 6	655 Participants
Part I: Number of Participants With Relapses (Confirmed and Unconfirmed) From First Dose of Fingolimod Month 0 to Month 12	992 Participants
Part I: Number of Participants With Relapses (Confirmed and Unconfirmed) From First Dose of Fingolimod Month 0 to Month 24	1461 Participants
Part I: Number of Participants With Relapses (Confirmed and Unconfirmed) From First Dose of Fingolimod Month 0 to Month 36	1794 Participants
Part I: Number of Participants With Relapses (Confirmed and Unconfirmed) From First Dose of Fingolimod Month 0 to Month 48	2127 Participants
Part I: Number of Participants With Relapses (Confirmed and Unconfirmed) From First Dose of Fingolimod Month 0 to Month 60	2383 Participants
Part I: Number of Participants With Relapses (Confirmed and Unconfirmed) From First Dose of Fingolimod Month 0 to Month 72	2616 Participants
Part I: Number of Participants With Relapses (Confirmed and Unconfirmed) From First Dose of Fingolimod Month 0 to Month 84	2793 Participants
Part I: Number of Participants With Relapses (Confirmed and Unconfirmed) From First Dose of Fingolimod Month 0 to Month 96	2944 Participants
Part I: Number of Participants With Relapses (Confirmed and Unconfirmed) From First Dose of Fingolimod Month 0 to Month 108	3036 Participants
Part I: Number of Participants With Relapses (Confirmed and Unconfirmed) From First Dose of Fingolimod Month 0 to Month 120	3063 Participants
Part I: Number of Participants With Relapses (Confirmed and Unconfirmed) From First Dose of Fingolimod Month 0 to Month 132	3072 Participants
Part I: Number of Participants With Relapses (Confirmed and Unconfirmed) From First Dose of Fingolimod Month 0 to Month 144	3075 Participants
Part I: Number of Participants With Relapses (Confirmed and Unconfirmed) From First Dose of Fingolimod Month 0 to Month 156	3079 Participants
Part I: Number of Participants With Relapses (Confirmed and Unconfirmed) From First Dose of Fingolimod Month 0 to end of Study	2970 Participants
Part I: Number of Participants With Relapses (Confirmed and Unconfirmed) From First Dose of Fingolimod Month 0 to end of Follow-up	3079 Participants

SECONDARY outcome

Timeframe: Month 0 (Core Baseline) to End of Study (an average of Month 156)

Population: Fingolimod full analysis set. Only participants with an observed value were considered for the analysis.

Annualized rate of new/newly enlarging T2 lesions (ARneT2) is defined as the number of new or newly enlarging T2 lesions experienced during a specific period of time adjusted to a one-year period. ARneT2 was calculated as follows: (total number of new/newly enlarging T2 lesions) / (total number of days in the study for all patients for that specific period of time) x 365.25.Month 0 is the first dose of fingolimod study drug among all studies in which patient participated. Only descriptive analysis performed.

Outcome measures

Outcome measures
Measure	Fingolimod 0.5 mg/Day n=4046 Participants Open-label fingolimod 0.5 mg, taken orally once daily
Part I: Annualized Rates of New or Newly Enlarging T2 Lesions (ARneT2) Compared With First Dose of Fingolimod Month 0 to Month 3	12.324 Annual number of T2 lesions per patient
Part I: Annualized Rates of New or Newly Enlarging T2 Lesions (ARneT2) Compared With First Dose of Fingolimod Month 0 to Month 6	2.073 Annual number of T2 lesions per patient
Part I: Annualized Rates of New or Newly Enlarging T2 Lesions (ARneT2) Compared With First Dose of Fingolimod Month 0 to Month 12	1.360 Annual number of T2 lesions per patient
Part I: Annualized Rates of New or Newly Enlarging T2 Lesions (ARneT2) Compared With First Dose of Fingolimod Month 0 to Month 24	1.042 Annual number of T2 lesions per patient
Part I: Annualized Rates of New or Newly Enlarging T2 Lesions (ARneT2) Compared With First Dose of Fingolimod Month 0 to Month 36	1.011 Annual number of T2 lesions per patient
Part I: Annualized Rates of New or Newly Enlarging T2 Lesions (ARneT2) Compared With First Dose of Fingolimod Month 0 to Month 48	1.008 Annual number of T2 lesions per patient
Part I: Annualized Rates of New or Newly Enlarging T2 Lesions (ARneT2) Compared With First Dose of Fingolimod Month 0 to Month 60	0.957 Annual number of T2 lesions per patient
Part I: Annualized Rates of New or Newly Enlarging T2 Lesions (ARneT2) Compared With First Dose of Fingolimod Month 0 to Month 72	0.963 Annual number of T2 lesions per patient
Part I: Annualized Rates of New or Newly Enlarging T2 Lesions (ARneT2) Compared With First Dose of Fingolimod Month 0 to Month 84	0.906 Annual number of T2 lesions per patient
Part I: Annualized Rates of New or Newly Enlarging T2 Lesions (ARneT2) Compared With First Dose of Fingolimod Month 0 to Month 96	0.813 Annual number of T2 lesions per patient
Part I: Annualized Rates of New or Newly Enlarging T2 Lesions (ARneT2) Compared With First Dose of Fingolimod Month 0 to Month 108	0.713 Annual number of T2 lesions per patient
Part I: Annualized Rates of New or Newly Enlarging T2 Lesions (ARneT2) Compared With First Dose of Fingolimod Month 0 to Month 120	0.702 Annual number of T2 lesions per patient
Part I: Annualized Rates of New or Newly Enlarging T2 Lesions (ARneT2) Compared With First Dose of Fingolimod Month 0 to Month 132	0.659 Annual number of T2 lesions per patient
Part I: Annualized Rates of New or Newly Enlarging T2 Lesions (ARneT2) Compared With First Dose of Fingolimod Month 0 to Month 144	0.681 Annual number of T2 lesions per patient
Part I: Annualized Rates of New or Newly Enlarging T2 Lesions (ARneT2) Compared With First Dose of Fingolimod Month 0 to Month 156	0.637 Annual number of T2 lesions per patient
Part I: Annualized Rates of New or Newly Enlarging T2 Lesions (ARneT2) Compared With First Dose of Fingolimod Month 0 to end of study	0.751 Annual number of T2 lesions per patient

SECONDARY outcome

Timeframe: Month 3 to End of Study (Study Completion Visit)

Population: Fingolimod full analysis set. Only participants with an observed value were considered for the analysis.

Total volume of T2 lesions was summarized by presenting descriptive statistics for change from first dose of fingolimod baseline values by visit.

Outcome measures

Outcome measures
Measure	Fingolimod 0.5 mg/Day n=4046 Participants Open-label fingolimod 0.5 mg, taken orally once daily
Part I: Change From First Dose of Fingolimod in Total T2 Lesions Volume T2 volume change at Month 3	-749.5 mm^3 Standard Deviation 5269.04
Part I: Change From First Dose of Fingolimod in Total T2 Lesions Volume T2 volume change at Month 6	-207.0 mm^3 Standard Deviation 1385.64
Part I: Change From First Dose of Fingolimod in Total T2 Lesions Volume T2 volume change at Month 12	-55.0 mm^3 Standard Deviation 1700.16
Part I: Change From First Dose of Fingolimod in Total T2 Lesions Volume T2 volume change at Month 24	16.2 mm^3 Standard Deviation 2009.87
Part I: Change From First Dose of Fingolimod in Total T2 Lesions Volume T2 volume change at Month 36	235.8 mm^3 Standard Deviation 2519.39
Part I: Change From First Dose of Fingolimod in Total T2 Lesions Volume T2 volume change at Month 48	875.1 mm^3 Standard Deviation 4145.99
Part I: Change From First Dose of Fingolimod in Total T2 Lesions Volume T2 volume change at Month 60	1546.3 mm^3 Standard Deviation 4556.51
Part I: Change From First Dose of Fingolimod in Total T2 Lesions Volume T2 volume change at Month 72	1719.2 mm^3 Standard Deviation 5184.27
Part I: Change From First Dose of Fingolimod in Total T2 Lesions Volume T2 volume change at Month 84	1635.8 mm^3 Standard Deviation 5075.13
Part I: Change From First Dose of Fingolimod in Total T2 Lesions Volume T2 volume change at Month 96	1303.9 mm^3 Standard Deviation 4712.78
Part I: Change From First Dose of Fingolimod in Total T2 Lesions Volume T2 volume change at Month 108	1562.0 mm^3 Standard Deviation 4654.67
Part I: Change From First Dose of Fingolimod in Total T2 Lesions Volume T2 volume change at Month 120	1393.1 mm^3 Standard Deviation 4908.76
Part I: Change From First Dose of Fingolimod in Total T2 Lesions Volume T2 volume change at Month 132	905.9 mm^3 Standard Deviation 3960.94
Part I: Change From First Dose of Fingolimod in Total T2 Lesions Volume T2 volume change at Month 144	702.7 mm^3 Standard Deviation 3765.80
Part I: Change From First Dose of Fingolimod in Total T2 Lesions Volume T2 volume change at Month 156	274.0 mm^3 Standard Deviation 5784.85
Part I: Change From First Dose of Fingolimod in Total T2 Lesions Volume T2 volume change at End of Study	1588.5 mm^3 Standard Deviation 5157.00

SECONDARY outcome

Timeframe: Month 3 to End of Study (Study Completion Visit)

Population: Fingolimod full analysis set. Only participants with an observed value were considered for the analysis.

T1 hypointense lesion (black hole) volume was summarized by presenting descriptive statistics for change from first dose of fingolimod baseline values by visit.

Outcome measures

Outcome measures
Measure	Fingolimod 0.5 mg/Day n=4046 Participants Open-label fingolimod 0.5 mg, taken orally once daily
Part I: Change From First Dose of Fingolimod in Total T1 Hypointense Lesions Volume T1 volume change at Month 3	-519.8 mm^3 Standard Deviation 1339.62
Part I: Change From First Dose of Fingolimod in Total T1 Hypointense Lesions Volume T1 volume change at Month 12	49.1 mm^3 Standard Deviation 718.77
Part I: Change From First Dose of Fingolimod in Total T1 Hypointense Lesions Volume T1 volume change at Month 24	64.1 mm^3 Standard Deviation 786.02
Part I: Change From First Dose of Fingolimod in Total T1 Hypointense Lesions Volume T1 volume change at Month 36	151.08 mm^3 Standard Deviation 1001.28
Part I: Change From First Dose of Fingolimod in Total T1 Hypointense Lesions Volume T1 volume change at Month 48	524.8 mm^3 Standard Deviation 1706.26
Part I: Change From First Dose of Fingolimod in Total T1 Hypointense Lesions Volume T1 volume change at Month 60	853.6 mm^3 Standard Deviation 1957.74
Part I: Change From First Dose of Fingolimod in Total T1 Hypointense Lesions Volume T1 volume change at Month 72	975.7 mm^3 Standard Deviation 2637.67
Part I: Change From First Dose of Fingolimod in Total T1 Hypointense Lesions Volume T1 volume change at Month 84	930.1 mm^3 Standard Deviation 2471.70
Part I: Change From First Dose of Fingolimod in Total T1 Hypointense Lesions Volume T1 volume change at Month 96	753.4 mm^3 Standard Deviation 1845.63
Part I: Change From First Dose of Fingolimod in Total T1 Hypointense Lesions Volume T1 volume change at Month 108	628.7 mm^3 Standard Deviation 1922.45
Part I: Change From First Dose of Fingolimod in Total T1 Hypointense Lesions Volume T1 volume change at Month 120	817.3 mm^3 Standard Deviation 2198.58
Part I: Change From First Dose of Fingolimod in Total T1 Hypointense Lesions Volume T1 volume change at Month 132	726.7 mm^3 Standard Deviation NA NA: Not estimable due to insufficient number of participants with events
Part I: Change From First Dose of Fingolimod in Total T1 Hypointense Lesions Volume T1 volume change at End of Study	800.6 mm^3 Standard Deviation 2247.27

SECONDARY outcome

Timeframe: Month 3 to Month 156

Population: Fingolimod full analysis set. Only participants with an observed value were considered for the analysis.

Descriptive statistics on percent brain volume change from first dose of fingolimod baseline were presented by visit. A negative change from baseline indicates improvement.

Outcome measures

Outcome measures
Measure	Fingolimod 0.5 mg/Day n=4046 Participants Open-label fingolimod 0.5 mg, taken orally once daily
Part I: Percent Brain Volume Change (PBVC) Relative to First Dose of Fingolimod Percent volume change at Month 3	-0.19 Percent change Standard Deviation 0.660
Part I: Percent Brain Volume Change (PBVC) Relative to First Dose of Fingolimod Percent volume change at Month 6	-0.20 Percent change Standard Deviation 0.801
Part I: Percent Brain Volume Change (PBVC) Relative to First Dose of Fingolimod Percent volume change at Month 12	-0.36 Percent change Standard Deviation 0.901
Part I: Percent Brain Volume Change (PBVC) Relative to First Dose of Fingolimod Percent volume change at Month 24	-0.74 Percent change Standard Deviation 1.209
Part I: Percent Brain Volume Change (PBVC) Relative to First Dose of Fingolimod Percent volume change at Month 36	-1.03 Percent change Standard Deviation 1.541
Part I: Percent Brain Volume Change (PBVC) Relative to First Dose of Fingolimod Percent volume change at Month 48	-1.44 Percent change Standard Deviation 1.851
Part I: Percent Brain Volume Change (PBVC) Relative to First Dose of Fingolimod Percent volume change at Month 60	-1.65 Percent change Standard Deviation 2.196
Part I: Percent Brain Volume Change (PBVC) Relative to First Dose of Fingolimod Percent volume change at Month 72	-2.02 Percent change Standard Deviation 2.514
Part I: Percent Brain Volume Change (PBVC) Relative to First Dose of Fingolimod Percent volume change at Month 84	-2.38 Percent change Standard Deviation 2.638
Part I: Percent Brain Volume Change (PBVC) Relative to First Dose of Fingolimod Percent volume change at Month 96	-2.41 Percent change Standard Deviation 2.607
Part I: Percent Brain Volume Change (PBVC) Relative to First Dose of Fingolimod Percent volume change at Month 108	-2.91 Percent change Standard Deviation 2.863
Part I: Percent Brain Volume Change (PBVC) Relative to First Dose of Fingolimod Percent volume change at Month 120	-3.42 Percent change Standard Deviation 2.911
Part I: Percent Brain Volume Change (PBVC) Relative to First Dose of Fingolimod Percent volume change at Month 132	-4.61 Percent change Standard Deviation 2.511
Part I: Percent Brain Volume Change (PBVC) Relative to First Dose of Fingolimod Percent volume change at Month 144	-4.21 Percent change Standard Deviation 2.778
Part I: Percent Brain Volume Change (PBVC) Relative to First Dose of Fingolimod Percent volume change at Month 156	-4.33 Percent change Standard Deviation 3.146

SECONDARY outcome

Timeframe: Month 3 to Month 156

Population: Fingolimod full analysis set. Only participants with an observed value were considered for the analysis.

The annualized rate of brain volume change is an "averaged annual percentage change" in brain volume. ARBA was calculated as: ARBA = \[(SIENA/100+1) \^ (365.25/#days)-1\]\*100 where SIENA=(Vk/V0-1)\*100 and Vk is the brain volume at time k, V0 is the brain volume at time 0 and k is the total number of days in the study for all patients for that specific period of time) × 365.25. Only descriptive analysis performed.

Outcome measures

Outcome measures
Measure	Fingolimod 0.5 mg/Day n=4046 Participants Open-label fingolimod 0.5 mg, taken orally once daily
Part I: Annualized Rate of Brain Atrophy (ARBA) Relative to First Dose of Fingolimod Month 156	-0.35 Ratio Standard Deviation 0.256
Part I: Annualized Rate of Brain Atrophy (ARBA) Relative to First Dose of Fingolimod Month 3	-0.73 Ratio Standard Deviation 2.834
Part I: Annualized Rate of Brain Atrophy (ARBA) Relative to First Dose of Fingolimod Month 6	-0.39 Ratio Standard Deviation 1.590
Part I: Annualized Rate of Brain Atrophy (ARBA) Relative to First Dose of Fingolimod Month 12	-0.35 Ratio Standard Deviation 0.891
Part I: Annualized Rate of Brain Atrophy (ARBA) Relative to First Dose of Fingolimod Month 24	-0.37 Ratio Standard Deviation 0.615
Part I: Annualized Rate of Brain Atrophy (ARBA) Relative to First Dose of Fingolimod Month 36	-0.35 Ratio Standard Deviation 0.522
Part I: Annualized Rate of Brain Atrophy (ARBA) Relative to First Dose of Fingolimod Month 48	-0.37 Ratio Standard Deviation 0.480
Part I: Annualized Rate of Brain Atrophy (ARBA) Relative to First Dose of Fingolimod Month 60	-0.34 Ratio Standard Deviation 0.451
Part I: Annualized Rate of Brain Atrophy (ARBA) Relative to First Dose of Fingolimod Month 72	-0.35 Ratio Standard Deviation 0.433
Part I: Annualized Rate of Brain Atrophy (ARBA) Relative to First Dose of Fingolimod Month 84	-0.35 Ratio Standard Deviation 0.395
Part I: Annualized Rate of Brain Atrophy (ARBA) Relative to First Dose of Fingolimod Month 96	-0.31 Ratio Standard Deviation 0.340
Part I: Annualized Rate of Brain Atrophy (ARBA) Relative to First Dose of Fingolimod Month 108	-0.33 Ratio Standard Deviation 0.326
Part I: Annualized Rate of Brain Atrophy (ARBA) Relative to First Dose of Fingolimod Month 120	-0.36 Ratio Standard Deviation 0.308
Part I: Annualized Rate of Brain Atrophy (ARBA) Relative to First Dose of Fingolimod Month 132	-0.43 Ratio Standard Deviation 0.240
Part I: Annualized Rate of Brain Atrophy (ARBA) Relative to First Dose of Fingolimod Month 144	-0.36 Ratio Standard Deviation 0.244

SECONDARY outcome

Timeframe: Month 12 to Month 156

Population: Fingolimod full analysis set

Disability progression was defined based on an increase in the EDSS score by 1.5 point for patients with a first dose of fingolimod (FDF) baseline EDSS score of 0, 1 point for patients with FDF baseline EDSS of \>=1 and \<=5.5, and by 0.5 points for patients with an FDF baseline EDSS\>5.5, confirmed after 6 months and all intermediate EDSS assessments. A 6-month confirmed disability progression was defined as a 6-month sustained increase from the reference (potential onset of progression) value in the EDSS scores. i.e., every EDSS score (scheduled or unscheduled) within a 6-month duration after the first progression should meet the progression criteria as specified above. The confirmation could only happen at a scheduled visit and in the absence of a relapse. Only descriptive analysis performed.

Outcome measures

Outcome measures
Measure	Fingolimod 0.5 mg/Day n=4046 Participants Open-label fingolimod 0.5 mg, taken orally once daily
Part I: Number of Participants With Confirmed 6-month Disability Progression After First Dose of Fingolimod Month 144	776 Participants
Part I: Number of Participants With Confirmed 6-month Disability Progression After First Dose of Fingolimod Month 12	212 Participants
Part I: Number of Participants With Confirmed 6-month Disability Progression After First Dose of Fingolimod Month 24	336 Participants
Part I: Number of Participants With Confirmed 6-month Disability Progression After First Dose of Fingolimod Month 36	434 Participants
Part I: Number of Participants With Confirmed 6-month Disability Progression After First Dose of Fingolimod Month 48	519 Participants
Part I: Number of Participants With Confirmed 6-month Disability Progression After First Dose of Fingolimod Month 60	590 Participants
Part I: Number of Participants With Confirmed 6-month Disability Progression After First Dose of Fingolimod Month 72	659 Participants
Part I: Number of Participants With Confirmed 6-month Disability Progression After First Dose of Fingolimod Month 84	714 Participants
Part I: Number of Participants With Confirmed 6-month Disability Progression After First Dose of Fingolimod Month 96	753 Participants
Part I: Number of Participants With Confirmed 6-month Disability Progression After First Dose of Fingolimod Month 108	767 Participants
Part I: Number of Participants With Confirmed 6-month Disability Progression After First Dose of Fingolimod Month 120	772 Participants
Part I: Number of Participants With Confirmed 6-month Disability Progression After First Dose of Fingolimod Month 132	775 Participants
Part I: Number of Participants With Confirmed 6-month Disability Progression After First Dose of Fingolimod Month 156	777 Participants

SECONDARY outcome

Timeframe: Month 3 to Month 6 Follow-up

Population: Fingolimod full analysis set. Only participants with an observed value were considered for the analysis.

The EDSS is a scale for assessing neurological impairment in MS (Kurtzke 1983) including (1) a series of scores in each of eight functional systems, and (2) the EDSS steps (ranging from 0 (normal) to 10 (death due to MS). The functional systems are Visual, Brain Stem, Pyramidal, Cerebellar, Sensory, Bowel and Bladder, Cerebral and Other functions. Based on the assessment of each FS, the participant's overall score is categorized as Improvement, Stable or Deterioration. If baseline EDSS score is \<=5, improvement is indicated by an EDSS score change of \<= -1, stable is indicated by an EDSS score change of \> -1 and \<= 0.5, deterioration is indicated by an EDSS score change of \> 0.5; if baseline EDSS score is \> 5, improvement is indicated by an EDSS score change of \<= -0.5, stable is indicated by an EDSS score change of \> -0.5 and \<= 0, deterioration is indicated by an EDSS score change of \> 0. Only descriptive analysis performed.

Outcome measures

Outcome measures
Measure	Fingolimod 0.5 mg/Day n=4046 Participants Open-label fingolimod 0.5 mg, taken orally once daily
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 3 · Improvement	374 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 3 · Stable	3126 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 3 · Deterioration	269 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 6 · Improvement	508 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 6 · Stable	2900 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 6 · Deterioration	340 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 9 · Improvement	482 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 9 · Stable	2425 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 9 · Deterioration	304 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 12 · Improvement	422 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 12 · Stable	1930 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 12 · Deterioration	322 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 15 · Improvement	405 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 15 · Stable	1764 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 15 · Deterioration	285 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 18 · Improvement	345 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 18 · Stable	1361 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 18 · Deterioration	271 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 21 · Improvement	376 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 21 · Stable	1524 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 21 · Deterioration	287 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 24 · Improvement	320 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 24 · Stable	1299 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 24 · Deterioration	294 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 27 · Improvement	313 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 27 · Stable	1271 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 27 · Deterioration	270 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 30 · Improvement	305 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 30 · Stable	1204 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 30 · Deterioration	287 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 33 · Improvement	326 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 33 · Stable	1172 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 33 · Deterioration	292 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 36 · Improvement	309 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 36 · Stable	1065 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 36 · Deterioration	288 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 39 · Improvement	284 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 39 · Stable	1015 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 39 · Deterioration	276 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 42 · Improvement	282 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 42 · Stable	948 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 42 · Deterioration	287 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 45 · Improvement	244 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 45 · Stable	875 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 45 · Deterioration	263 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 48 · Improvement	250 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 48 · Stable	838 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 48 · Deterioration	264 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 51 · Improvement	244 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 51 · Stable	784 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 51 · Deterioration	247 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 54 · Improvement	256 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 54 · Stable	788 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 54 · Deterioration	251 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 57 · Improvement	201 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 57 · Stable	694 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 57 · Deterioration	245 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 60 · Improvement	175 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 60 · Stable	577 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 60 · Deterioration	234 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 63 · Improvement	182 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 63 · Stable	540 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 63 · Deterioration	191 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 66 · Improvement	165 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 66 · Stable	499 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 66 · Deterioration	216 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 69 · Improvement	156 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 69 · Stable	503 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 69 · Deterioration	193 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 72 · Improvement	143 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 72 · Stable	440 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 72 · Deterioration	206 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 75 · Improvement	156 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 75 · Stable	437 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 75 · Deterioration	201 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 78 · Improvement	136 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 78 · Stable	398 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 78 · Deterioration	226 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 81 · Improvement	150 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 81 · Stable	456 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 81 · Deterioration	217 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 84 · Improvement	132 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 84 · Stable	407 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 84 · Deterioration	207 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 87 · Improvement	147 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 87 · Stable	450 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 87 · Deterioration	227 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 90 · Improvement	120 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 90 · Stable	413 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 90 · Deterioration	204 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 93 · Improvement	143 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 93 · Stable	386 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 93 · Deterioration	187 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 96 · Improvement	117 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 96 · Stable	375 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 96 · Deterioration	186 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 99 · Improvement	110 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 99 · Stable	325 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 99 · Deterioration	159 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 102 · Improvement	94 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 102 · Stable	283 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 102 · Deterioration	154 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 105 · Improvement	103 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 105 · Stable	261 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 105 · Deterioration	131 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 108 · Improvement	87 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 108 · Stable	287 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 108 · Deterioration	138 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 111 · Improvement	74 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 111 · Stable	198 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 111 · Deterioration	101 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 114 · Improvement	45 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 114 · Stable	181 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 114 · Deterioration	79 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 117 · Improvement	31 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 117 · Stable	94 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 117 · Deterioration	52 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 120 · Improvement	19 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 120 · Stable	88 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 120 · Deterioration	42 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 123 · Improvement	9 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 123 · Stable	36 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 123 · Deterioration	21 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 126 · Improvement	14 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 126 · Stable	45 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 126 · Deterioration	26 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 129 · Improvement	6 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 129 · Stable	18 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 129 · Deterioration	12 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 132 · Improvement	11 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 132 · Stable	36 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 132 · Deterioration	21 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 135 · Improvement	5 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 135 · Stable	19 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 135 · Deterioration	12 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 138 · Improvement	10 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 138 · Stable	39 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 138 · Deterioration	18 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 141 · Improvement	6 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 141 · Stable	18 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 141 · Deterioration	12 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 144 · Improvement	7 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 144 · Stable	30 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 144 · Deterioration	19 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 147 · Improvement	6 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 147 · Stable	21 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 147 · Deterioration	15 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 150 · Improvement	7 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 150 · Stable	22 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 150 · Deterioration	15 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 153 · Improvement	8 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 153 · Stable	16 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 153 · Deterioration	8 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 156 · Improvement	3 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 156 · Stable	9 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 156 · Deterioration	5 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 159 · Improvement	1 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 159 · Stable	2 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 159 · Deterioration	6 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 162 · Improvement	0 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 162 · Stable	1 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 162 · Deterioration	1 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score End of study · Improvement	610 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score End of study · Stable	2419 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score End of study · Deterioration	785 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 3 follow-up · Improvement	203 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 3 follow-up · Stable	907 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 3 follow-up · Deterioration	381 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 6 follow-up · Improvement	29 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 6 follow-up · Stable	111 Participants
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score Month 6 follow-up · Deterioration	88 Participants

SECONDARY outcome

Timeframe: Month 0 (Core Baseline) to End of Follow-up Visit (an average of 162 months)

Population: Fingolimod full analysis set. Only participants with an observed value were considered for the analysis.

Outcome measures

Outcome measures
Measure	Fingolimod 0.5 mg/Day n=4046 Participants Open-label fingolimod 0.5 mg, taken orally once daily
Part I: Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Baseline (BL)	2.39 EDDS Overall Score Standard Deviation 1.452
Part I: Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Change from BL at Month 3	-0.06 EDDS Overall Score Standard Deviation 0.638
Part I: Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Change from BL at Month 6	-0.07 EDDS Overall Score Standard Deviation 0.716
Part I: Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Change from BL at Month 9	-0.09 EDDS Overall Score Standard Deviation 0.750
Part I: Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Change from BL at Month 12	-0.07 EDDS Overall Score Standard Deviation 0.815
Part I: Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Change from BL at Month 15	-0.08 EDDS Overall Score Standard Deviation 0.814
Part I: Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Change from BL at Month 18	-0.05 EDDS Overall Score Standard Deviation 0.890
Part I: Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Change from BL at Month 21	-0.08 EDDS Overall Score Standard Deviation 0.876
Part I: Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Change from BL at Month 24	-0.01 EDDS Overall Score Standard Deviation 0.916
Part I: Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Change from BL at Month 27	-0.03 EDDS Overall Score Standard Deviation 0.932
Part I: Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Change from BL at Month 30	-0.00 EDDS Overall Score Standard Deviation 0.935
Part I: Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Change from BL at Month 33	-0.02 EDDS Overall Score Standard Deviation 0.951
Part I: Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Change from BL at Month 36	0.01 EDDS Overall Score Standard Deviation 0.997
Part I: Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Change from BL at Month 39	0.02 EDDS Overall Score Standard Deviation 0.963
Part I: Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Change from BL at Month 42	0.04 EDDS Overall Score Standard Deviation 1.015
Part I: Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Change from BL at Month 45	0.06 EDDS Overall Score Standard Deviation 1.006
Part I: Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Change from BL at Month 48	0.06 EDDS Overall Score Standard Deviation 1.063
Part I: Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Change from BL at Month 51	0.06 EDDS Overall Score Standard Deviation 1.071
Part I: Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Change from BL at Month 54	0.04 EDDS Overall Score Standard Deviation 1.120
Part I: Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Change from BL at Month 57	0.09 EDDS Overall Score Standard Deviation 1.077
Part I: Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Change from BL at Month 60	0.17 EDDS Overall Score Standard Deviation 1.144
Part I: Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Change from BL at Month 63	0.08 EDDS Overall Score Standard Deviation 1.123
Part I: Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Change from BL at Month 66	0.15 EDDS Overall Score Standard Deviation 1.220
Part I: Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Change from BL at Month 69	0.14 EDDS Overall Score Standard Deviation 1.116
Part I: Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Change from BL at Month 72	0.22 EDDS Overall Score Standard Deviation 1.205
Part I: Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Change from BL at Month 75	0.13 EDDS Overall Score Standard Deviation 1.159
Part I: Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Change from BL at Month 78	0.28 EDDS Overall Score Standard Deviation 1.259
Part I: Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Change from BL at Month 81	0.18 EDDS Overall Score Standard Deviation 1.158
Part I: Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Change from BL at Month 84	0.25 EDDS Overall Score Standard Deviation 1.236
Part I: Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Change from BL at Month 87	0.24 EDDS Overall Score Standard Deviation 1.206
Part I: Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Change from BL at Month 90	0.29 EDDS Overall Score Standard Deviation 1.282
Part I: Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Change from BL at Month 93	0.18 EDDS Overall Score Standard Deviation 1.219
Part I: Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Change from BL at Month 96	0.31 EDDS Overall Score Standard Deviation 1.355
Part I: Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Change from BL at Month 99	0.18 EDDS Overall Score Standard Deviation 1.220
Part I: Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Change from BL at Month 102	0.30 EDDS Overall Score Standard Deviation 1.332
Part I: Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Change from BL at Month 105	0.21 EDDS Overall Score Standard Deviation 1.320
Part I: Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Change from BL at Month 108	0.28 EDDS Overall Score Standard Deviation 1.270
Part I: Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Change from BL at Month 111	0.24 EDDS Overall Score Standard Deviation 1.343
Part I: Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Change from BL at Month 114	0.30 EDDS Overall Score Standard Deviation 1.258
Part I: Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Change from BL at Month 117	0.35 EDDS Overall Score Standard Deviation 1.389
Part I: Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Change from BL at Month 120	0.40 EDDS Overall Score Standard Deviation 1.271
Part I: Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Change from BL at Month 123	0.60 EDDS Overall Score Standard Deviation 1.302
Part I: Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Change from BL at Month 126	0.38 EDDS Overall Score Standard Deviation 1.441
Part I: Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Change from BL at Month 129	0.40 EDDS Overall Score Standard Deviation 1.448
Part I: Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Change from BL at Month 132	0.40 EDDS Overall Score Standard Deviation 1.450
Part I: Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Change from BL at Month 135	0.51 EDDS Overall Score Standard Deviation 1.519
Part I: Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Change from BL at Month 138	0.42 EDDS Overall Score Standard Deviation 1.527
Part I: Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Change from BL at Month 141	0.54 EDDS Overall Score Standard Deviation 1.509
Part I: Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Change from BL at Month 144	0.60 EDDS Overall Score Standard Deviation 1.553
Part I: Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Change from BL at Month 147	0.67 EDDS Overall Score Standard Deviation 1.640
Part I: Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Change from BL at Month 150	0.44 EDDS Overall Score Standard Deviation 1.483
Part I: Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Change from BL at Month 153	0.23 EDDS Overall Score Standard Deviation 1.534
Part I: Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Change from BL at Month 156	0.26 EDDS Overall Score Standard Deviation 1.427
Part I: Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Change from BL at Month 159	1.17 EDDS Overall Score Standard Deviation 1.369
Part I: Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Change from BL at Month 162	0.75 EDDS Overall Score Standard Deviation 1.061
Part I: Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Change from BL at End of study	0.14 EDDS Overall Score Standard Deviation 1.108
Part I: Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Change from BL at Month 3 follow-up	0.29 EDDS Overall Score Standard Deviation 1.248
Part I: Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Change from BL at Month 6 follow-up	0.56 EDDS Overall Score Standard Deviation 1.487

Adverse Events

Fingolimod 0.5 mg/Day

Serious events: 515 serious events

Other events: 2125 other events

Deaths: 16 deaths

Serious adverse events

Serious adverse events
Measure	Fingolimod 0.5 mg/Day n=4083 participants at risk Open-label fingolimod 0.5 mg, taken orally once daily
Blood and lymphatic system disorders Anaemia	0.07% 3/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Blood and lymphatic system disorders Immune thrombocytopenic purpura	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Blood and lymphatic system disorders Iron deficiency anaemia	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Blood and lymphatic system disorders Leukopenia	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Blood and lymphatic system disorders Lymphadenopathy	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Blood and lymphatic system disorders Lymphopenia	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Blood and lymphatic system disorders Thrombocytopenia	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Cardiac disorders Angina pectoris	0.07% 3/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Cardiac disorders Atrial fibrillation	0.15% 6/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Cardiac disorders Atrioventricular block first degree	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Cardiac disorders Bradycardia	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Cardiac disorders Cardiac arrest	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Cardiac disorders Cardiac failure	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Cardiac disorders Cardio-respiratory arrest	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Cardiac disorders Cardiopulmonary failure	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Cardiac disorders Cardiovascular insufficiency	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Cardiac disorders Cyanosis	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Cardiac disorders Myocardial infarction	0.10% 4/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Cardiac disorders Pericarditis	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Cardiac disorders Supraventricular tachycardia	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Cardiac disorders Ventricular extrasystoles	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Cardiac disorders Ventricular tachycardia	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Congenital, familial and genetic disorders Atrial septal defect	0.07% 3/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Congenital, familial and genetic disorders Bicuspid aortic valve	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Congenital, familial and genetic disorders Congenital cytomegalovirus infection	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Congenital, familial and genetic disorders Congenital knee dislocation	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Ear and labyrinth disorders Vertigo	0.10% 4/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Endocrine disorders Hyperprolactinaemia	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Endocrine disorders Thyroid mass	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Eye disorders Photophobia	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Eye disorders Retinal detachment	0.05% 2/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Eye disorders Retinal haemorrhage	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Eye disorders Retinal vein thrombosis	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Gastrointestinal disorders Abdominal adhesions	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Gastrointestinal disorders Abdominal hernia	0.05% 2/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Gastrointestinal disorders Abdominal pain	0.10% 4/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Gastrointestinal disorders Abdominal pain lower	0.05% 2/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Gastrointestinal disorders Anal fissure	0.10% 4/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Gastrointestinal disorders Barrett's oesophagus	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Gastrointestinal disorders Colitis	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Gastrointestinal disorders Crohn's disease	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Gastrointestinal disorders Diarrhoea	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Gastrointestinal disorders Duodenal ulcer	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Gastrointestinal disorders Duodenal ulcer perforation	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Gastrointestinal disorders Enterocolitis	0.05% 2/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Gastrointestinal disorders Flatulence	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Gastrointestinal disorders Food poisoning	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Gastrointestinal disorders Gastric disorder	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Gastrointestinal disorders Gastric ulcer	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Gastrointestinal disorders Gastritis	0.05% 2/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Gastrointestinal disorders Haematochezia	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Gastrointestinal disorders Haemorrhoids	0.05% 2/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Gastrointestinal disorders Inguinal hernia	0.07% 3/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Gastrointestinal disorders Irritable bowel syndrome	0.05% 2/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Gastrointestinal disorders Large intestine polyp	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Gastrointestinal disorders Nausea	0.05% 2/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Gastrointestinal disorders Proctalgia	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Gastrointestinal disorders Proctitis	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Gastrointestinal disorders Rectal haemorrhage	0.05% 2/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Gastrointestinal disorders Rectal polyp	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Gastrointestinal disorders Umbilical hernia	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Gastrointestinal disorders Vomiting	0.07% 3/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
General disorders Death	0.05% 2/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
General disorders Death neonatal	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
General disorders Fat tissue increased	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
General disorders Fatigue	0.12% 5/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
General disorders Gait disturbance	0.05% 2/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
General disorders Hernia	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
General disorders Hypothermia	0.05% 2/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
General disorders Influenza like illness	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
General disorders Multiple organ dysfunction syndrome	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
General disorders Non-cardiac chest pain	0.05% 2/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
General disorders Peripheral swelling	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
General disorders Pyrexia	0.12% 5/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
General disorders Vascular stent stenosis	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Hepatobiliary disorders Biliary colic	0.12% 5/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Hepatobiliary disorders Biliary cyst	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Hepatobiliary disorders Biliary dyskinesia	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Hepatobiliary disorders Cholangitis acute	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Hepatobiliary disorders Cholecystitis	0.10% 4/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Hepatobiliary disorders Cholecystitis chronic	0.07% 3/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Hepatobiliary disorders Cholelithiasis	0.24% 10/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Hepatobiliary disorders Drug-induced liver injury	0.05% 2/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Hepatobiliary disorders Hepatitis acute	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Hepatobiliary disorders Liver disorder	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Immune system disorders Haemophagocytic lymphohistiocytosis	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Immune system disorders Immunodeficiency	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Infections and infestations Abdominal abscess	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Infections and infestations Abdominal sepsis	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Infections and infestations Appendicitis	0.24% 10/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Infections and infestations Appendicitis perforated	0.05% 2/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Infections and infestations Bartholin's abscess	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Infections and infestations Bronchitis	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Infections and infestations Cellulitis	0.15% 6/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Infections and infestations Cystitis	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Infections and infestations Dermatitis infected	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Infections and infestations Diverticulitis	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Infections and infestations Epididymitis	0.05% 2/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Infections and infestations Furuncle	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Infections and infestations Gastroenteritis	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Infections and infestations Gastroenteritis viral	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Infections and infestations Gastrointestinal infection	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Infections and infestations Groin abscess	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Infections and infestations Helicobacter infection	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Infections and infestations Hepatitis A	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Infections and infestations Hepatitis C	0.05% 2/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Infections and infestations Hepatitis E	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Infections and infestations Herpes simplex encephalitis	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Infections and infestations Herpes zoster	0.22% 9/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Infections and infestations Herpes zoster infection neurological	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Infections and infestations Histoplasmosis	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Infections and infestations Infected dermal cyst	0.05% 2/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Infections and infestations Infection	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Infections and infestations Influenza	0.05% 2/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Infections and infestations Injection site abscess	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Infections and infestations Intervertebral discitis	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Infections and infestations Lower respiratory tract infection	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Infections and infestations Lung infection	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Infections and infestations Lymphangitis	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Infections and infestations Mastoiditis	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Infections and infestations Meningitis cryptococcal	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Infections and infestations Meningoencephalitis herpetic	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Infections and infestations Orchitis	0.05% 2/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Infections and infestations Pelvic inflammatory disease	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Infections and infestations Peritonsillar abscess	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Infections and infestations Pilonidal cyst	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Infections and infestations Pneumonia	0.34% 14/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Infections and infestations Pneumonia bacterial	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Infections and infestations Pulmonary tuberculosis	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Infections and infestations Pyelitis	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Infections and infestations Pyelonephritis	0.05% 2/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Infections and infestations Renal abscess	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Infections and infestations Respiratory tract infection	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Infections and infestations Salpingitis	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Infections and infestations Salpingo-oophoritis	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Infections and infestations Sepsis	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Infections and infestations Sinusitis	0.05% 2/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Infections and infestations Spermatic cord funiculitis	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Infections and infestations Staphylococcal infection	0.05% 2/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Infections and infestations Subcutaneous abscess	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Infections and infestations Upper respiratory tract infection	0.05% 2/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Infections and infestations Urinary tract infection	0.34% 14/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Infections and infestations Urinary tract infection enterococcal	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Infections and infestations Urosepsis	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Infections and infestations Viraemia	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Infections and infestations Viral diarrhoea	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Infections and infestations Viral infection	0.05% 2/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Infections and infestations Vulval abscess	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Injury, poisoning and procedural complications Alcohol poisoning	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Injury, poisoning and procedural complications Ankle fracture	0.15% 6/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Injury, poisoning and procedural complications Arthropod bite	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Injury, poisoning and procedural complications Chest injury	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Injury, poisoning and procedural complications Clavicle fracture	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Injury, poisoning and procedural complications Concussion	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Injury, poisoning and procedural complications Craniocerebral injury	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Injury, poisoning and procedural complications Facial bones fracture	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Injury, poisoning and procedural complications Fall	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Injury, poisoning and procedural complications Femoral neck fracture	0.05% 2/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Injury, poisoning and procedural complications Femur fracture	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Injury, poisoning and procedural complications Fibula fracture	0.05% 2/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Injury, poisoning and procedural complications Foot fracture	0.05% 2/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Injury, poisoning and procedural complications Head injury	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Injury, poisoning and procedural complications Hip fracture	0.05% 2/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Injury, poisoning and procedural complications Humerus fracture	0.05% 2/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Injury, poisoning and procedural complications Joint injury	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Injury, poisoning and procedural complications Kidney contusion	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Injury, poisoning and procedural complications Ligament rupture	0.05% 2/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Injury, poisoning and procedural complications Lower limb fracture	0.05% 2/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Injury, poisoning and procedural complications Meniscus injury	0.05% 2/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Injury, poisoning and procedural complications Multiple injuries	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Injury, poisoning and procedural complications Muscle injury	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Injury, poisoning and procedural complications Near drowning	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Injury, poisoning and procedural complications Patella fracture	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Injury, poisoning and procedural complications Pelvic fracture	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Injury, poisoning and procedural complications Pubis fracture	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Injury, poisoning and procedural complications Radius fracture	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Injury, poisoning and procedural complications Rib fracture	0.05% 2/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Injury, poisoning and procedural complications Road traffic accident	0.12% 5/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Injury, poisoning and procedural complications Skull fracture	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Injury, poisoning and procedural complications Spinal fracture	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Injury, poisoning and procedural complications Splenic rupture	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Injury, poisoning and procedural complications Tibia fracture	0.10% 4/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Injury, poisoning and procedural complications Traumatic haematoma	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Injury, poisoning and procedural complications Traumatic spinal cord compression	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Injury, poisoning and procedural complications Ulna fracture	0.07% 3/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Injury, poisoning and procedural complications Ulnar nerve injury	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Injury, poisoning and procedural complications Upper limb fracture	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Injury, poisoning and procedural complications Vaginal laceration	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Injury, poisoning and procedural complications Wrist fracture	0.05% 2/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Investigations Hepatic enzyme increased	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Investigations Lymphocyte count decreased	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Investigations Weight decreased	0.05% 2/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Metabolism and nutrition disorders Dehydration	0.05% 2/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Metabolism and nutrition disorders Hyperamylasaemia	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Metabolism and nutrition disorders Obesity	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Musculoskeletal and connective tissue disorders Amyotrophy	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Musculoskeletal and connective tissue disorders Arthralgia	0.05% 2/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Musculoskeletal and connective tissue disorders Back pain	0.17% 7/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Musculoskeletal and connective tissue disorders Bursitis	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Musculoskeletal and connective tissue disorders Chondromalacia	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Musculoskeletal and connective tissue disorders Chondropathy	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Musculoskeletal and connective tissue disorders Compartment syndrome	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Musculoskeletal and connective tissue disorders Foot deformity	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.20% 8/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Musculoskeletal and connective tissue disorders Jaw disorder	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Musculoskeletal and connective tissue disorders Joint instability	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Musculoskeletal and connective tissue disorders Joint swelling	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Musculoskeletal and connective tissue disorders Lateral patellar compression syndrome	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Musculoskeletal and connective tissue disorders Mobility decreased	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Musculoskeletal and connective tissue disorders Muscular weakness	0.07% 3/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.15% 6/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Musculoskeletal and connective tissue disorders Osteonecrosis	0.05% 2/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Musculoskeletal and connective tissue disorders Pain in extremity	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Musculoskeletal and connective tissue disorders Rhabdomyolysis	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Musculoskeletal and connective tissue disorders Rotator cuff syndrome	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Musculoskeletal and connective tissue disorders Spinal column stenosis	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Musculoskeletal and connective tissue disorders Synovial cyst	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Musculoskeletal and connective tissue disorders Torticollis	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma of colon	0.07% 3/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) B-cell lymphoma	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	0.73% 30/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Benign hydatidiform mole	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Benign neoplasm of thyroid gland	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Benign ovarian tumour	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder cancer	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bone giant cell tumour	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bowen's disease	0.07% 3/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Brain neoplasm benign	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.27% 11/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cervix carcinoma	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer metastatic	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Desmoid tumour	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Extranodal marginal zone B-cell lymphoma (MALT type)	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Fibroadenoma of breast	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastrointestinal neoplasm	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Intraductal proliferative breast lesion	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Invasive lobular breast carcinoma	0.05% 2/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Laryngeal squamous cell carcinoma	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Leiomyoma	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung adenocarcinoma	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant melanoma	0.07% 3/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Melanocytic naevus	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Meningioma	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to lymph nodes	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to spine	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasm	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Non-Hodgkin's lymphoma	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Ovarian adenoma	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Ovarian cancer metastatic	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pancreatic carcinoma	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Papilloma	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Phyllodes tumour	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.07% 3/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Rectal cancer	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal cancer	0.07% 3/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal cell carcinoma	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Seminoma	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Small cell lung cancer	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma	0.22% 9/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of lung	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of skin	0.07% 3/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Thyroid adenoma	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine cancer	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine leiomyoma	0.24% 10/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Nervous system disorders Altered state of consciousness	0.05% 2/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Nervous system disorders Brain hypoxia	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Nervous system disorders Carotid artery occlusion	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Nervous system disorders Cauda equina syndrome	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Nervous system disorders Central nervous system lesion	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Nervous system disorders Cerebellar infarction	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Nervous system disorders Cerebral infarction	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Nervous system disorders Cerebral venous thrombosis	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Nervous system disorders Cerebrovascular accident	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Nervous system disorders Coma	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Nervous system disorders Demyelination	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Nervous system disorders Dizziness	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Nervous system disorders Epilepsy	0.20% 8/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Nervous system disorders Facial spasm	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Nervous system disorders Fine motor skill dysfunction	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Nervous system disorders Focal dyscognitive seizures	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Nervous system disorders Generalised tonic-clonic seizure	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Nervous system disorders Headache	0.10% 4/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Nervous system disorders Hemianopia homonymous	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Nervous system disorders Hemiparesis	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Nervous system disorders Hyperaesthesia	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Nervous system disorders Hypoaesthesia	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Nervous system disorders Intracranial aneurysm	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Nervous system disorders Ischaemic stroke	0.07% 3/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Nervous system disorders Lacunar infarction	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Nervous system disorders Loss of consciousness	0.05% 2/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Nervous system disorders Migraine	0.05% 2/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Nervous system disorders Multiple sclerosis	0.07% 3/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Nervous system disorders Multiple sclerosis relapse	0.83% 34/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Nervous system disorders Muscle spasticity	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Nervous system disorders Myelitis transverse	0.05% 2/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Nervous system disorders Neuralgia	0.05% 2/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Nervous system disorders Optic neuritis	0.07% 3/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Nervous system disorders Paraesthesia	0.05% 2/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Nervous system disorders Partial seizures	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Nervous system disorders Presyncope	0.05% 2/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Nervous system disorders Sciatica	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Nervous system disorders Secondary progressive multiple sclerosis	0.05% 2/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Nervous system disorders Seizure	0.07% 3/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Nervous system disorders Spinal cord compression	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Nervous system disorders Status epilepticus	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Nervous system disorders Subarachnoid haemorrhage	0.07% 3/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Nervous system disorders Syncope	0.10% 4/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Nervous system disorders Tension headache	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Nervous system disorders Thrombotic stroke	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Nervous system disorders Transient ischaemic attack	0.07% 3/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Nervous system disorders Trigeminal neuralgia	0.07% 3/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Nervous system disorders Uhthoff's phenomenon	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Nervous system disorders Ulnar nerve palsy	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Nervous system disorders Wernicke's encephalopathy	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Pregnancy, puerperium and perinatal conditions Abortion	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Pregnancy, puerperium and perinatal conditions Abortion spontaneous	0.24% 10/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Pregnancy, puerperium and perinatal conditions Ectopic pregnancy	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Pregnancy, puerperium and perinatal conditions Hyperemesis gravidarum	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Product Issues Device dislocation	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Psychiatric disorders Acute stress disorder	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Psychiatric disorders Adjustment disorder with depressed mood	0.05% 2/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Psychiatric disorders Aggression	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Psychiatric disorders Anxiety	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Psychiatric disorders Bipolar I disorder	0.05% 2/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Psychiatric disorders Completed suicide	0.07% 3/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Psychiatric disorders Confusional state	0.05% 2/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Psychiatric disorders Depression	0.22% 9/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Psychiatric disorders Drug dependence	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Psychiatric disorders Eating disorder	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Psychiatric disorders Major depression	0.05% 2/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Psychiatric disorders Mania	0.07% 3/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Psychiatric disorders Mental disorder	0.05% 2/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Psychiatric disorders Panic attack	0.05% 2/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Psychiatric disorders Persecutory delusion	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Psychiatric disorders Personality change	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Psychiatric disorders Personality change due to a general medical condition	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Psychiatric disorders Psychogenic seizure	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Psychiatric disorders Psychotic disorder	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Psychiatric disorders Somatic symptom disorder	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Psychiatric disorders Stress	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Psychiatric disorders Suicidal ideation	0.12% 5/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Psychiatric disorders Suicide attempt	0.07% 3/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Renal and urinary disorders Acute kidney injury	0.05% 2/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Renal and urinary disorders Calculus urinary	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Renal and urinary disorders Hydronephrosis	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Renal and urinary disorders Nephrolithiasis	0.07% 3/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Renal and urinary disorders Renal haemorrhage	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Renal and urinary disorders Urinary incontinence	0.05% 2/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Renal and urinary disorders Urinary retention	0.05% 2/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Reproductive system and breast disorders Adnexa uteri cyst	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Reproductive system and breast disorders Benign prostatic hyperplasia	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Reproductive system and breast disorders Breast calcifications	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Reproductive system and breast disorders Cervical dysplasia	0.17% 7/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Reproductive system and breast disorders Dysfunctional uterine bleeding	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Reproductive system and breast disorders Endometriosis	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Reproductive system and breast disorders Gynaecomastia	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Reproductive system and breast disorders Metrorrhagia	0.07% 3/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Reproductive system and breast disorders Ovarian cyst	0.10% 4/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Reproductive system and breast disorders Postmenopausal haemorrhage	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Reproductive system and breast disorders Uterine cyst	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Reproductive system and breast disorders Uterine haemorrhage	0.07% 3/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Reproductive system and breast disorders Uterine polyp	0.10% 4/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Respiratory, thoracic and mediastinal disorders Acute respiratory distress syndrome	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Respiratory, thoracic and mediastinal disorders Aspiration	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Respiratory, thoracic and mediastinal disorders Asthma	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Respiratory, thoracic and mediastinal disorders Cough	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Respiratory, thoracic and mediastinal disorders Haemothorax	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Respiratory, thoracic and mediastinal disorders Nasal polyps	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.12% 5/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Skin and subcutaneous tissue disorders Alopecia	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Skin and subcutaneous tissue disorders Dermatitis	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Skin and subcutaneous tissue disorders Dermatitis contact	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Skin and subcutaneous tissue disorders Erythema	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Skin and subcutaneous tissue disorders Erythema annulare	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Skin and subcutaneous tissue disorders Rash	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Skin and subcutaneous tissue disorders Skin erosion	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Surgical and medical procedures Abortion induced	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Vascular disorders Aneurysm	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Vascular disorders Aortic aneurysm	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Vascular disorders Deep vein thrombosis	0.10% 4/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Vascular disorders Hypertension	0.05% 2/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Vascular disorders Hypertensive crisis	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Vascular disorders Hypoperfusion	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Vascular disorders Peripheral artery thrombosis	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Vascular disorders Peripheral venous disease	0.05% 2/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Vascular disorders Phlebitis	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Vascular disorders Shock haemorrhagic	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Vascular disorders Vasculitis	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Vascular disorders Venous stenosis	0.02% 1/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.

Other adverse events

Other adverse events
Measure	Fingolimod 0.5 mg/Day n=4083 participants at risk Open-label fingolimod 0.5 mg, taken orally once daily
Blood and lymphatic system disorders Lymphopenia	5.4% 219/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
General disorders Fatigue	5.7% 232/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Infections and infestations Bronchitis	5.2% 214/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Infections and infestations Influenza	6.7% 275/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Infections and infestations Nasopharyngitis	17.3% 706/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Infections and infestations Upper respiratory tract infection	8.5% 346/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Infections and infestations Urinary tract infection	8.2% 335/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Metabolism and nutrition disorders Hypercholesterolaemia	5.2% 212/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Musculoskeletal and connective tissue disorders Arthralgia	5.1% 208/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Musculoskeletal and connective tissue disorders Back pain	6.8% 279/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Nervous system disorders Headache	8.5% 348/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Psychiatric disorders Depression	5.0% 205/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.
Vascular disorders Hypertension	6.0% 243/4083 • Adverse events were collected from first dose of study treatment in Study Part I until end of study treatment in Study Part II plus 6 weeks post treatment, up to a maximum duration of 8 years.

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.
Publication restrictions are in place

Restriction type: OTHER