Trial Outcomes & Findings for Disease Control and Safety in Patients With Relapsing Remitting Multiple Sclerosis (RRMS) Switching From Natalizumab to Fingolimod (NCT NCT01499667)

Last Updated: 2014-08-08

Results Overview

Active lesions were measured on brain MRI scans, performed at week 8, compared to the prior scan. The primary variable was analyzed by fitting a negative binomial regression model adjusted for washout group.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

142 participants

Primary outcome timeframe

Number of active T2 lesions from last natalizumab dose through 8 weeks of fingolimod treatment

Results posted on

2014-08-08

Participant Flow

Of the 158 patients screened, 142 patients were randomized.

142 Participants were randomized to 3 washout groups in a ratio of 1:1:1

Participant milestones

Participant milestones
Measure	8-week Washout + Fingolimod (FTY720) 8-week washout (8 weeks no treatment) followed by 24 weeks of treatment with fingolimod 0.5mg once a day	12-week Washout + Fingolimod (FTY720) 12-week washout (8 weeks no treatment and 4 weeks placebo) followed by 20 weeks of treatment with fingolimod 0.5mg once a day	16-week Washout + Fingolimod (FTY720) 16-week washout (8 weeks no treatment and 8 weeks placebo) followed by 16 weeks of treatment with fingolimod 0.5mg once a day
Overall Study STARTED	50	42	50
Overall Study Full Analysis Set (FAS)	49	42	50
Overall Study Modified Full Analysis Set	41	29	39
Overall Study COMPLETED	41	31	40
Overall Study NOT COMPLETED	9	11	10

Reasons for withdrawal

Reasons for withdrawal
Measure	8-week Washout + Fingolimod (FTY720) 8-week washout (8 weeks no treatment) followed by 24 weeks of treatment with fingolimod 0.5mg once a day	12-week Washout + Fingolimod (FTY720) 12-week washout (8 weeks no treatment and 4 weeks placebo) followed by 20 weeks of treatment with fingolimod 0.5mg once a day	16-week Washout + Fingolimod (FTY720) 16-week washout (8 weeks no treatment and 8 weeks placebo) followed by 16 weeks of treatment with fingolimod 0.5mg once a day
Overall Study administrative problems	4	5	5
Overall Study Protocol Violation	1	3	2
Overall Study Adverse Event	0	2	2
Overall Study Withdrawal by Subject	2	1	1
Overall Study Lack of Efficacy	2	0	0

Baseline Characteristics

Disease Control and Safety in Patients With Relapsing Remitting Multiple Sclerosis (RRMS) Switching From Natalizumab to Fingolimod

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	8-week Washout + Fingolimod (FTY720) n=50 Participants 8-week washout (8 weeks no treatment) followed by 24 weeks of treatment with fingolimod 0.5mg once a day	12-week Washout + Fingolimod (FTY720) n=42 Participants 12-week washout (8 weeks no treatment and 4 weeks placebo) followed by 20 weeks of treatment with fingolimod 0.5mg once a day	16-week Washout + Fingolimod (FTY720) n=50 Participants 16-week washout (8 weeks no treatment and 8 weeks placebo) followed by 16 weeks of treatment with fingolimod	Total n=142 Participants Total of all reporting groups
Age, Continuous	41.2 Years STANDARD_DEVIATION 10.102 • n=5 Participants	41.9 Years STANDARD_DEVIATION 7.445 • n=7 Participants	41.8 Years STANDARD_DEVIATION 8.552 • n=5 Participants	41.6 Years STANDARD_DEVIATION 8.780 • n=4 Participants
Sex: Female, Male Female	39 Participants n=5 Participants	21 Participants n=7 Participants	32 Participants n=5 Participants	92 Participants n=4 Participants
Sex: Female, Male Male	11 Participants n=5 Participants	21 Participants n=7 Participants	18 Participants n=5 Participants	50 Participants n=4 Participants

PRIMARY outcome

Timeframe: Number of active T2 lesions from last natalizumab dose through 8 weeks of fingolimod treatment

Population: The modified Full Analysis Set (mFAS) included all patients in the Full Analysis Set who completed 8 weeks of fingolimod treatment and provided an MRI scan at this time point. The analysis of primary variable was performed on the mFAS.

Outcome measures

Outcome measures
Measure	8-week Washout + Fingolimod (FTY720) n=41 Participants 8-week washout (8 weeks no treatment) followed by 24 weeks of treatment with fingolimod 0.5mg once a day	12-week Washout + Fingolimod (FTY720) n=29 Participants 12-week washout (8 weeks no treatment and 4 weeks placebo) followed by 20 weeks of treatment with fingolimod 0.5mg once a day	16-week Washout + Fingolimod (FTY720) n=39 Participants 16-week washout (8 weeks no treatment and 8 weeks placebo) followed by 16 weeks of treatment with fingolimod 0.5mg once a day
Number of Active (New or Newly Enlarging) T2 Lesions From the Last Natalizumab Infusion (Baseline) Through 8 Weeks of Fingolimod Treatment	2.1 Count of Active T2 Lesions Standard Deviation 7.24	1.7 Count of Active T2 Lesions Standard Deviation 3.78	8.2 Count of Active T2 Lesions Standard Deviation 16.81

SECONDARY outcome

Timeframe: 8, 12 and 16 weeks (number of active T2 lesions during the washout period only)

Population: The Full Analysis Set (FAS) included all randomized patients who had at least one recorded dose of natalizumab at the Week 0 visit, analyzed according to the washout group assigned at randomization

Lesions were measured by MRIs and the number of active (new or newly enlarging) T2 lesions was calculated from baseline to beginning of treatment.

Outcome measures

Outcome measures
Measure	8-week Washout + Fingolimod (FTY720) n=49 Participants 8-week washout (8 weeks no treatment) followed by 24 weeks of treatment with fingolimod 0.5mg once a day	12-week Washout + Fingolimod (FTY720) n=42 Participants 12-week washout (8 weeks no treatment and 4 weeks placebo) followed by 20 weeks of treatment with fingolimod 0.5mg once a day	16-week Washout + Fingolimod (FTY720) n=50 Participants 16-week washout (8 weeks no treatment and 8 weeks placebo) followed by 16 weeks of treatment with fingolimod 0.5mg once a day
Number of Active (New or Newly Enlarging) T2 Lesions From the Last Natalizumab Infusion (Baseline) up to the Initiation of Fingolimod Treatment	0.4 Count of active T2 lesions Standard Deviation 2.71	2.1 Count of active T2 lesions Standard Deviation 11.15	3.6 Count of active T2 lesions Standard Deviation 7.54

SECONDARY outcome

Timeframe: Number of active T2 lesions during 8 wks of fingolimod treatment

Lesions were measured by MRIs and the number of active (new or newly enlarging) T2 lesions was calculated for first 8 weeks of fingolimod treatment.

Outcome measures

Outcome measures
Measure	8-week Washout + Fingolimod (FTY720) n=49 Participants 8-week washout (8 weeks no treatment) followed by 24 weeks of treatment with fingolimod 0.5mg once a day	12-week Washout + Fingolimod (FTY720) n=42 Participants 12-week washout (8 weeks no treatment and 4 weeks placebo) followed by 20 weeks of treatment with fingolimod 0.5mg once a day	16-week Washout + Fingolimod (FTY720) n=50 Participants 16-week washout (8 weeks no treatment and 8 weeks placebo) followed by 16 weeks of treatment with fingolimod 0.5mg once a day
Number of Active (New or Newly Enlarging) T2 Lesions During the First 8 Weeks of Fingolimod Treatment	1.5 Count of Active T2 Lesions Standard Deviation 4.56	2.1 Count of Active T2 Lesions Standard Deviation 5.50	4.2 Count of Active T2 Lesions Standard Deviation 10.24

SECONDARY outcome

Timeframe: Baseline up to 24 weeks

Lesions will be measured by MRIs and the number of active (new or newly enlarging) T2 lesions will be calculated for 24 weeks from baseline.

Outcome measures

Outcome measures
Measure	8-week Washout + Fingolimod (FTY720) n=49 Participants 8-week washout (8 weeks no treatment) followed by 24 weeks of treatment with fingolimod 0.5mg once a day	12-week Washout + Fingolimod (FTY720) n=42 Participants 12-week washout (8 weeks no treatment and 4 weeks placebo) followed by 20 weeks of treatment with fingolimod 0.5mg once a day	16-week Washout + Fingolimod (FTY720) n=50 Participants 16-week washout (8 weeks no treatment and 8 weeks placebo) followed by 16 weeks of treatment with fingolimod 0.5mg once a day
Number of Active (New or Newly Enlarging) T2 Lesions During the 24 Weeks After the Last Natalizumab Infusion (Baseline)	3.2 Count of Active T2 Lesions Standard Deviation 10.07	4.4 Count of Active T2 Lesions Standard Deviation 16.01	7.7 Count of Active T2 Lesions Standard Deviation 16.28

SECONDARY outcome

Timeframe: Baseline to week 16 and week 32

Kurtzke's Expanded Disability Status Scale (EDSS) measures the changes in neurologic impairment, either chronic (progression over time), or acute (MS relapses). The EDSS steps range from 0 (normal) to 10 (death due to MS). Relapse severity is assessed based on severity of neurologic impairment as evaluated using the EDSS.

Outcome measures

Outcome measures
Measure	8-week Washout + Fingolimod (FTY720) n=49 Participants 8-week washout (8 weeks no treatment) followed by 24 weeks of treatment with fingolimod 0.5mg once a day	12-week Washout + Fingolimod (FTY720) n=42 Participants 12-week washout (8 weeks no treatment and 4 weeks placebo) followed by 20 weeks of treatment with fingolimod 0.5mg once a day	16-week Washout + Fingolimod (FTY720) n=50 Participants 16-week washout (8 weeks no treatment and 8 weeks placebo) followed by 16 weeks of treatment with fingolimod 0.5mg once a day
Change From Baseline in Expanded Disability Status Scale (EDSS) by Washout Group Week 16 (n=40, 33, 39)	0.11 Units on a scale Standard Deviation 0.330	-0.03 Units on a scale Standard Deviation 0.529	0.23 Units on a scale Standard Deviation 0.706
Change From Baseline in Expanded Disability Status Scale (EDSS) by Washout Group Week 32 (n= 40,30,39)	0.11 Units on a scale Standard Deviation 0.625	-0.13 Units on a scale Standard Deviation 0.524	0.08 Units on a scale Standard Deviation 0.748

SECONDARY outcome

Timeframe: 8 weeks and 24 weeks

Gadolinium-enhancing lesions will be measured on post-contrast T1-weighted brain MRI scans

Outcome measures

Outcome measures
Measure	8-week Washout + Fingolimod (FTY720) n=49 Participants 8-week washout (8 weeks no treatment) followed by 24 weeks of treatment with fingolimod 0.5mg once a day	12-week Washout + Fingolimod (FTY720) n=42 Participants 12-week washout (8 weeks no treatment and 4 weeks placebo) followed by 20 weeks of treatment with fingolimod 0.5mg once a day	16-week Washout + Fingolimod (FTY720) n=50 Participants 16-week washout (8 weeks no treatment and 8 weeks placebo) followed by 16 weeks of treatment with fingolimod 0.5mg once a day
Cumulative Number of Gadolinium-enhancing T1 Lesions From the Last Natalizumab Infusion Week 8 (n=1,1,0)	25.0 Number of Gd enhanced T1 Lesions Standard Deviation 0	2.0 Number of Gd enhanced T1 Lesions Standard Deviation 0	NA Number of Gd enhanced T1 Lesions Standard Deviation NA No data collected for this time point
Cumulative Number of Gadolinium-enhancing T1 Lesions From the Last Natalizumab Infusion Week 24 (n=10,12,21)	6.3 Number of Gd enhanced T1 Lesions Standard Deviation 9.45	3.4 Number of Gd enhanced T1 Lesions Standard Deviation 4.54	3.6 Number of Gd enhanced T1 Lesions Standard Deviation 4.49

SECONDARY outcome

Timeframe: Baseline to maximum of 16 weeks

Population: The Safety Set included all randomized patients, analyzed according to the washout group most closely corresponding to the day on which they first received fingolimod

Adverse events were summarized by the number of patients having any adverse event overall.

Outcome measures

Outcome measures
Measure	8-week Washout + Fingolimod (FTY720) n=50 Participants 8-week washout (8 weeks no treatment) followed by 24 weeks of treatment with fingolimod 0.5mg once a day	12-week Washout + Fingolimod (FTY720) n=42 Participants 12-week washout (8 weeks no treatment and 4 weeks placebo) followed by 20 weeks of treatment with fingolimod 0.5mg once a day	16-week Washout + Fingolimod (FTY720) n=50 Participants 16-week washout (8 weeks no treatment and 8 weeks placebo) followed by 16 weeks of treatment with fingolimod 0.5mg once a day
Number of Participants With Adverse Events (AE), Serious Adverse Events (SAE) and Death During Washout Period Any Adverse Events	13 participants	12 participants	25 participants
Number of Participants With Adverse Events (AE), Serious Adverse Events (SAE) and Death During Washout Period Serious Adverse Events	0 participants	0 participants	1 participants
Number of Participants With Adverse Events (AE), Serious Adverse Events (SAE) and Death During Washout Period Death	0 participants	0 participants	0 participants

SECONDARY outcome

Timeframe: Baseline to maximum of 16 weeks

Population: The Safety Set included all randomized patients, analyzed according to the washout group most closely corresponding to the day on which they first received fingolimod

Adverse events were summarized by the number of patients having any adverse event overall.

Outcome measures

Outcome measures
Measure	8-week Washout + Fingolimod (FTY720) n=50 Participants 8-week washout (8 weeks no treatment) followed by 24 weeks of treatment with fingolimod 0.5mg once a day	12-week Washout + Fingolimod (FTY720) n=42 Participants 12-week washout (8 weeks no treatment and 4 weeks placebo) followed by 20 weeks of treatment with fingolimod 0.5mg once a day	16-week Washout + Fingolimod (FTY720) n=50 Participants 16-week washout (8 weeks no treatment and 8 weeks placebo) followed by 16 weeks of treatment with fingolimod 0.5mg once a day
Number of Participants With Adverse Events (AE), Serious Adverse Events (SAE) and Death During Fingolimod Treatment Any Adverse Events	35 participants	20 participants	28 participants
Number of Participants With Adverse Events (AE), Serious Adverse Events (SAE) and Death During Fingolimod Treatment Serious Adverse Events	2 participants	5 participants	3 participants
Number of Participants With Adverse Events (AE), Serious Adverse Events (SAE) and Death During Fingolimod Treatment Death	0 participants	0 participants	0 participants

Adverse Events

8-week Washout + Fingolimod (FTY720)

Serious events: 2 serious events

Other events: 17 other events

Deaths: 0 deaths

12-week Washout + Fingolimod (FTY720)

Serious events: 5 serious events

Other events: 7 other events

Deaths: 0 deaths

16-week Washout + Fingolimod (FTY720)

Serious events: 4 serious events

Other events: 14 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	8-week Washout + Fingolimod (FTY720) n=50 participants at risk 8-week washout (8 weeks no treatment) followed by 24 weeks of treatment with fingolimod 0.5mg once a day	12-week Washout + Fingolimod (FTY720) n=42 participants at risk 12-week washout (8 weeks no treatment and 4 weeks placebo) followed by 20 weeks of treatment with fingolimod 0.5mg once a day	16-week Washout + Fingolimod (FTY720) n=50 participants at risk 16-week washout (8 weeks no treatment and 8 weeks placebo) followed by 16 weeks of treatment with fingolimod 0.5mg once a day
Infections and infestations Nasopharyngitis	14.0% 7/50 Safety Set (SS): The Safety Set included all randomized patients, analyzed according to the washout group most closely corresponding to the day on which they first received fingolimod. Safety and tolerability analysis were performed on the SS unless otherwise specified.	2.4% 1/42 Safety Set (SS): The Safety Set included all randomized patients, analyzed according to the washout group most closely corresponding to the day on which they first received fingolimod. Safety and tolerability analysis were performed on the SS unless otherwise specified.	4.0% 2/50 Safety Set (SS): The Safety Set included all randomized patients, analyzed according to the washout group most closely corresponding to the day on which they first received fingolimod. Safety and tolerability analysis were performed on the SS unless otherwise specified.
Infections and infestations Oral herpes	2.0% 1/50 Safety Set (SS): The Safety Set included all randomized patients, analyzed according to the washout group most closely corresponding to the day on which they first received fingolimod. Safety and tolerability analysis were performed on the SS unless otherwise specified.	7.1% 3/42 Safety Set (SS): The Safety Set included all randomized patients, analyzed according to the washout group most closely corresponding to the day on which they first received fingolimod. Safety and tolerability analysis were performed on the SS unless otherwise specified.	2.0% 1/50 Safety Set (SS): The Safety Set included all randomized patients, analyzed according to the washout group most closely corresponding to the day on which they first received fingolimod. Safety and tolerability analysis were performed on the SS unless otherwise specified.
Infections and infestations Sinusitis	4.0% 2/50 Safety Set (SS): The Safety Set included all randomized patients, analyzed according to the washout group most closely corresponding to the day on which they first received fingolimod. Safety and tolerability analysis were performed on the SS unless otherwise specified.	2.4% 1/42 Safety Set (SS): The Safety Set included all randomized patients, analyzed according to the washout group most closely corresponding to the day on which they first received fingolimod. Safety and tolerability analysis were performed on the SS unless otherwise specified.	6.0% 3/50 Safety Set (SS): The Safety Set included all randomized patients, analyzed according to the washout group most closely corresponding to the day on which they first received fingolimod. Safety and tolerability analysis were performed on the SS unless otherwise specified.
Infections and infestations Urinary tract infection	6.0% 3/50 Safety Set (SS): The Safety Set included all randomized patients, analyzed according to the washout group most closely corresponding to the day on which they first received fingolimod. Safety and tolerability analysis were performed on the SS unless otherwise specified.	2.4% 1/42 Safety Set (SS): The Safety Set included all randomized patients, analyzed according to the washout group most closely corresponding to the day on which they first received fingolimod. Safety and tolerability analysis were performed on the SS unless otherwise specified.	0.00% 0/50 Safety Set (SS): The Safety Set included all randomized patients, analyzed according to the washout group most closely corresponding to the day on which they first received fingolimod. Safety and tolerability analysis were performed on the SS unless otherwise specified.
Musculoskeletal and connective tissue disorders Myalgia	6.0% 3/50 Safety Set (SS): The Safety Set included all randomized patients, analyzed according to the washout group most closely corresponding to the day on which they first received fingolimod. Safety and tolerability analysis were performed on the SS unless otherwise specified.	0.00% 0/42 Safety Set (SS): The Safety Set included all randomized patients, analyzed according to the washout group most closely corresponding to the day on which they first received fingolimod. Safety and tolerability analysis were performed on the SS unless otherwise specified.	0.00% 0/50 Safety Set (SS): The Safety Set included all randomized patients, analyzed according to the washout group most closely corresponding to the day on which they first received fingolimod. Safety and tolerability analysis were performed on the SS unless otherwise specified.
Nervous system disorders Dizziness	6.0% 3/50 Safety Set (SS): The Safety Set included all randomized patients, analyzed according to the washout group most closely corresponding to the day on which they first received fingolimod. Safety and tolerability analysis were performed on the SS unless otherwise specified.	2.4% 1/42 Safety Set (SS): The Safety Set included all randomized patients, analyzed according to the washout group most closely corresponding to the day on which they first received fingolimod. Safety and tolerability analysis were performed on the SS unless otherwise specified.	6.0% 3/50 Safety Set (SS): The Safety Set included all randomized patients, analyzed according to the washout group most closely corresponding to the day on which they first received fingolimod. Safety and tolerability analysis were performed on the SS unless otherwise specified.
Nervous system disorders Headache	10.0% 5/50 Safety Set (SS): The Safety Set included all randomized patients, analyzed according to the washout group most closely corresponding to the day on which they first received fingolimod. Safety and tolerability analysis were performed on the SS unless otherwise specified.	7.1% 3/42 Safety Set (SS): The Safety Set included all randomized patients, analyzed according to the washout group most closely corresponding to the day on which they first received fingolimod. Safety and tolerability analysis were performed on the SS unless otherwise specified.	20.0% 10/50 Safety Set (SS): The Safety Set included all randomized patients, analyzed according to the washout group most closely corresponding to the day on which they first received fingolimod. Safety and tolerability analysis were performed on the SS unless otherwise specified.
Psychiatric disorders Depression	2.0% 1/50 Safety Set (SS): The Safety Set included all randomized patients, analyzed according to the washout group most closely corresponding to the day on which they first received fingolimod. Safety and tolerability analysis were performed on the SS unless otherwise specified.	2.4% 1/42 Safety Set (SS): The Safety Set included all randomized patients, analyzed according to the washout group most closely corresponding to the day on which they first received fingolimod. Safety and tolerability analysis were performed on the SS unless otherwise specified.	6.0% 3/50 Safety Set (SS): The Safety Set included all randomized patients, analyzed according to the washout group most closely corresponding to the day on which they first received fingolimod. Safety and tolerability analysis were performed on the SS unless otherwise specified.
Respiratory, thoracic and mediastinal disorders Cough	6.0% 3/50 Safety Set (SS): The Safety Set included all randomized patients, analyzed according to the washout group most closely corresponding to the day on which they first received fingolimod. Safety and tolerability analysis were performed on the SS unless otherwise specified.	0.00% 0/42 Safety Set (SS): The Safety Set included all randomized patients, analyzed according to the washout group most closely corresponding to the day on which they first received fingolimod. Safety and tolerability analysis were performed on the SS unless otherwise specified.	2.0% 1/50 Safety Set (SS): The Safety Set included all randomized patients, analyzed according to the washout group most closely corresponding to the day on which they first received fingolimod. Safety and tolerability analysis were performed on the SS unless otherwise specified.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	8.0% 4/50 Safety Set (SS): The Safety Set included all randomized patients, analyzed according to the washout group most closely corresponding to the day on which they first received fingolimod. Safety and tolerability analysis were performed on the SS unless otherwise specified.	0.00% 0/42 Safety Set (SS): The Safety Set included all randomized patients, analyzed according to the washout group most closely corresponding to the day on which they first received fingolimod. Safety and tolerability analysis were performed on the SS unless otherwise specified.	0.00% 0/50 Safety Set (SS): The Safety Set included all randomized patients, analyzed according to the washout group most closely corresponding to the day on which they first received fingolimod. Safety and tolerability analysis were performed on the SS unless otherwise specified.

Additional Information

Study Director

Novartis Pharnaceuticals

Phone: 862-778-8300

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 pooled data (i.e.,data from all sites) in clinical trial or disclosure of trial results in their entirety.
Publication restrictions are in place

Restriction type: OTHER

Measure	8-week Washout + Fingolimod (FTY720) n=50 participants at risk 8-week washout (8 weeks no treatment) followed by 24 weeks of treatment with fingolimod 0.5mg once a day	12-week Washout + Fingolimod (FTY720) n=42 participants at risk 12-week washout (8 weeks no treatment and 4 weeks placebo) followed by 20 weeks of treatment with fingolimod 0.5mg once a day	16-week Washout + Fingolimod (FTY720) n=50 participants at risk 16-week washout (8 weeks no treatment and 8 weeks placebo) followed by 16 weeks of treatment with fingolimod 0.5mg once a day
Cardiac disorders Bradycardia	0.00% 0/50 Safety Set (SS): The Safety Set included all randomized patients, analyzed according to the washout group most closely corresponding to the day on which they first received fingolimod. Safety and tolerability analysis were performed on the SS unless otherwise specified.	0.00% 0/42 Safety Set (SS): The Safety Set included all randomized patients, analyzed according to the washout group most closely corresponding to the day on which they first received fingolimod. Safety and tolerability analysis were performed on the SS unless otherwise specified.	2.0% 1/50 Safety Set (SS): The Safety Set included all randomized patients, analyzed according to the washout group most closely corresponding to the day on which they first received fingolimod. Safety and tolerability analysis were performed on the SS unless otherwise specified.
Hepatobiliary disorders Cholecystitis acute	0.00% 0/50 Safety Set (SS): The Safety Set included all randomized patients, analyzed according to the washout group most closely corresponding to the day on which they first received fingolimod. Safety and tolerability analysis were performed on the SS unless otherwise specified.	2.4% 1/42 Safety Set (SS): The Safety Set included all randomized patients, analyzed according to the washout group most closely corresponding to the day on which they first received fingolimod. Safety and tolerability analysis were performed on the SS unless otherwise specified.	0.00% 0/50 Safety Set (SS): The Safety Set included all randomized patients, analyzed according to the washout group most closely corresponding to the day on which they first received fingolimod. Safety and tolerability analysis were performed on the SS unless otherwise specified.
Hepatobiliary disorders Cholelithiasis	0.00% 0/50 Safety Set (SS): The Safety Set included all randomized patients, analyzed according to the washout group most closely corresponding to the day on which they first received fingolimod. Safety and tolerability analysis were performed on the SS unless otherwise specified.	2.4% 1/42 Safety Set (SS): The Safety Set included all randomized patients, analyzed according to the washout group most closely corresponding to the day on which they first received fingolimod. Safety and tolerability analysis were performed on the SS unless otherwise specified.	0.00% 0/50 Safety Set (SS): The Safety Set included all randomized patients, analyzed according to the washout group most closely corresponding to the day on which they first received fingolimod. Safety and tolerability analysis were performed on the SS unless otherwise specified.
Infections and infestations Pharyngitis	0.00% 0/50 Safety Set (SS): The Safety Set included all randomized patients, analyzed according to the washout group most closely corresponding to the day on which they first received fingolimod. Safety and tolerability analysis were performed on the SS unless otherwise specified.	2.4% 1/42 Safety Set (SS): The Safety Set included all randomized patients, analyzed according to the washout group most closely corresponding to the day on which they first received fingolimod. Safety and tolerability analysis were performed on the SS unless otherwise specified.	0.00% 0/50 Safety Set (SS): The Safety Set included all randomized patients, analyzed according to the washout group most closely corresponding to the day on which they first received fingolimod. Safety and tolerability analysis were performed on the SS unless otherwise specified.
Infections and infestations Pneumonia	2.0% 1/50 Safety Set (SS): The Safety Set included all randomized patients, analyzed according to the washout group most closely corresponding to the day on which they first received fingolimod. Safety and tolerability analysis were performed on the SS unless otherwise specified.	0.00% 0/42 Safety Set (SS): The Safety Set included all randomized patients, analyzed according to the washout group most closely corresponding to the day on which they first received fingolimod. Safety and tolerability analysis were performed on the SS unless otherwise specified.	0.00% 0/50 Safety Set (SS): The Safety Set included all randomized patients, analyzed according to the washout group most closely corresponding to the day on which they first received fingolimod. Safety and tolerability analysis were performed on the SS unless otherwise specified.
Injury, poisoning and procedural complications Femur fracture	2.0% 1/50 Safety Set (SS): The Safety Set included all randomized patients, analyzed according to the washout group most closely corresponding to the day on which they first received fingolimod. Safety and tolerability analysis were performed on the SS unless otherwise specified.	0.00% 0/42 Safety Set (SS): The Safety Set included all randomized patients, analyzed according to the washout group most closely corresponding to the day on which they first received fingolimod. Safety and tolerability analysis were performed on the SS unless otherwise specified.	0.00% 0/50 Safety Set (SS): The Safety Set included all randomized patients, analyzed according to the washout group most closely corresponding to the day on which they first received fingolimod. Safety and tolerability analysis were performed on the SS unless otherwise specified.
Investigations Electrocardiogram T wave inversion	0.00% 0/50 Safety Set (SS): The Safety Set included all randomized patients, analyzed according to the washout group most closely corresponding to the day on which they first received fingolimod. Safety and tolerability analysis were performed on the SS unless otherwise specified.	0.00% 0/42 Safety Set (SS): The Safety Set included all randomized patients, analyzed according to the washout group most closely corresponding to the day on which they first received fingolimod. Safety and tolerability analysis were performed on the SS unless otherwise specified.	2.0% 1/50 Safety Set (SS): The Safety Set included all randomized patients, analyzed according to the washout group most closely corresponding to the day on which they first received fingolimod. Safety and tolerability analysis were performed on the SS unless otherwise specified.
Investigations Heart rate decreased	0.00% 0/50 Safety Set (SS): The Safety Set included all randomized patients, analyzed according to the washout group most closely corresponding to the day on which they first received fingolimod. Safety and tolerability analysis were performed on the SS unless otherwise specified.	2.4% 1/42 Safety Set (SS): The Safety Set included all randomized patients, analyzed according to the washout group most closely corresponding to the day on which they first received fingolimod. Safety and tolerability analysis were performed on the SS unless otherwise specified.	0.00% 0/50 Safety Set (SS): The Safety Set included all randomized patients, analyzed according to the washout group most closely corresponding to the day on which they first received fingolimod. Safety and tolerability analysis were performed on the SS unless otherwise specified.
Nervous system disorders Epilepsy	0.00% 0/50 Safety Set (SS): The Safety Set included all randomized patients, analyzed according to the washout group most closely corresponding to the day on which they first received fingolimod. Safety and tolerability analysis were performed on the SS unless otherwise specified.	2.4% 1/42 Safety Set (SS): The Safety Set included all randomized patients, analyzed according to the washout group most closely corresponding to the day on which they first received fingolimod. Safety and tolerability analysis were performed on the SS unless otherwise specified.	0.00% 0/50 Safety Set (SS): The Safety Set included all randomized patients, analyzed according to the washout group most closely corresponding to the day on which they first received fingolimod. Safety and tolerability analysis were performed on the SS unless otherwise specified.
Nervous system disorders Multiple sclerosis relapse	0.00% 0/50 Safety Set (SS): The Safety Set included all randomized patients, analyzed according to the washout group most closely corresponding to the day on which they first received fingolimod. Safety and tolerability analysis were performed on the SS unless otherwise specified.	0.00% 0/42 Safety Set (SS): The Safety Set included all randomized patients, analyzed according to the washout group most closely corresponding to the day on which they first received fingolimod. Safety and tolerability analysis were performed on the SS unless otherwise specified.	4.0% 2/50 Safety Set (SS): The Safety Set included all randomized patients, analyzed according to the washout group most closely corresponding to the day on which they first received fingolimod. Safety and tolerability analysis were performed on the SS unless otherwise specified.
Nervous system disorders Syncope	0.00% 0/50 Safety Set (SS): The Safety Set included all randomized patients, analyzed according to the washout group most closely corresponding to the day on which they first received fingolimod. Safety and tolerability analysis were performed on the SS unless otherwise specified.	2.4% 1/42 Safety Set (SS): The Safety Set included all randomized patients, analyzed according to the washout group most closely corresponding to the day on which they first received fingolimod. Safety and tolerability analysis were performed on the SS unless otherwise specified.	0.00% 0/50 Safety Set (SS): The Safety Set included all randomized patients, analyzed according to the washout group most closely corresponding to the day on which they first received fingolimod. Safety and tolerability analysis were performed on the SS unless otherwise specified.
Psychiatric disorders Depression suicidal	0.00% 0/50 Safety Set (SS): The Safety Set included all randomized patients, analyzed according to the washout group most closely corresponding to the day on which they first received fingolimod. Safety and tolerability analysis were performed on the SS unless otherwise specified.	2.4% 1/42 Safety Set (SS): The Safety Set included all randomized patients, analyzed according to the washout group most closely corresponding to the day on which they first received fingolimod. Safety and tolerability analysis were performed on the SS unless otherwise specified.	0.00% 0/50 Safety Set (SS): The Safety Set included all randomized patients, analyzed according to the washout group most closely corresponding to the day on which they first received fingolimod. Safety and tolerability analysis were performed on the SS unless otherwise specified.
Psychiatric disorders Major depression	0.00% 0/50 Safety Set (SS): The Safety Set included all randomized patients, analyzed according to the washout group most closely corresponding to the day on which they first received fingolimod. Safety and tolerability analysis were performed on the SS unless otherwise specified.	0.00% 0/42 Safety Set (SS): The Safety Set included all randomized patients, analyzed according to the washout group most closely corresponding to the day on which they first received fingolimod. Safety and tolerability analysis were performed on the SS unless otherwise specified.	2.0% 1/50 Safety Set (SS): The Safety Set included all randomized patients, analyzed according to the washout group most closely corresponding to the day on which they first received fingolimod. Safety and tolerability analysis were performed on the SS unless otherwise specified.
Psychiatric disorders Mental disorder due to a general medical condition	0.00% 0/50 Safety Set (SS): The Safety Set included all randomized patients, analyzed according to the washout group most closely corresponding to the day on which they first received fingolimod. Safety and tolerability analysis were performed on the SS unless otherwise specified.	0.00% 0/42 Safety Set (SS): The Safety Set included all randomized patients, analyzed according to the washout group most closely corresponding to the day on which they first received fingolimod. Safety and tolerability analysis were performed on the SS unless otherwise specified.	2.0% 1/50 Safety Set (SS): The Safety Set included all randomized patients, analyzed according to the washout group most closely corresponding to the day on which they first received fingolimod. Safety and tolerability analysis were performed on the SS unless otherwise specified.
Psychiatric disorders Personality change	0.00% 0/50 Safety Set (SS): The Safety Set included all randomized patients, analyzed according to the washout group most closely corresponding to the day on which they first received fingolimod. Safety and tolerability analysis were performed on the SS unless otherwise specified.	0.00% 0/42 Safety Set (SS): The Safety Set included all randomized patients, analyzed according to the washout group most closely corresponding to the day on which they first received fingolimod. Safety and tolerability analysis were performed on the SS unless otherwise specified.	2.0% 1/50 Safety Set (SS): The Safety Set included all randomized patients, analyzed according to the washout group most closely corresponding to the day on which they first received fingolimod. Safety and tolerability analysis were performed on the SS unless otherwise specified.