An Extension Study of the Efficacy and Safety of Fingolimod (FTY720) in Patients With Relapsing Multiple Sclerosis

• Sponsor: Novartis (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00670449
• Collaborator: Mitsubishi Tanabe Pharma Corporation (Industry)
• Enrollment: 143
• Locations: 20
• Arms: 3
• Duration (Months): 48
• Patients Per Site: 7.2
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This study was an extension study of NCT00537082. This study was designed to evaluate the efficacy and safety of long-term administration of 0.5 mg or 1.25 mg of fingolimod (FTY720) to relapsing multiple sclerosis.

Condition or Disease	Intervention/Treatment	Phase
Multiple Sclerosis	Drug: Fingolimod	Phase 2

Detailed Description

A decision was made to switch all patients on fingolimod 1.25 mg/day to fingolimod 0.5 mg/day in an amendment to the study protocol. The study became open-label with all patients receiving fingolimod 0.5 mg/day on 22 Feb 2010.

The efficacy data for Months 0-6 in this study report is from the core study NCT00537082.

Study Design

• Study Type: Interventional
• Actual Enrollment: 143 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: An Extension of the 6-month, Double-blind, Randomized, Placebo-controlled, Parallel-group, Multicenter Study Comparing Efficacy and Safety of FTY720 0.5 mg and 1.25 mg Administered Orally Once Daily in Patients With Relapsing Multiple Sclerosis
• Study Start Date: Apr 1, 2008
• Actual Primary Completion Date: Apr 1, 2012
• Actual Study Completion Date: Apr 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Fingolimod 0.5 mg Patients who received fingolimod 0.5 orally once daily in the core study continued on the same dose in this extension study.	Drug: Fingolimod; Fingolimod was supplied in capsules.; Other Names: Gilenya Imsera
Experimental: Fingolimod 1.25 mg Patients who received fingolimod 1.25 mg orally once daily in the core study continued on the same dose in this extension study.	Drug: Fingolimod; Fingolimod was supplied in capsules.; Other Names: Gilenya Imsera
Experimental: Placebo-fingolimod Patients who were randomized to placebo in the core study were re-randomized to either fingolimod 0.5 or 1.25 mg (1:1) orally once daily in this extension study.	Drug: Fingolimod; Fingolimod was supplied in capsules.; Other Names: Gilenya Imsera

Outcome Measures

Primary Outcome Measures

1. Percentage of Patients Free of Gd-enhanced T1 Weighted Magnetic Resonance Imaging (MRI) Lesions [Months 6, 9, 12, 18, 24, 36, and 48]

   To ensure consistency, MRI scans were evaluated centrally at the Institute of Neurotherapeutics in Kyoto, Japan. After checking the scans for completeness and quality, all scans were analyzed by blinded readers (experienced neurologists). The number of Gd-enhanced T1 weighted MRI lesions were counted and recorded. Lesions expanding through several slices were counted as only 1 lesion.

Secondary Outcome Measures

1. Percentage of Patients Free of New or Newly Enlarged T2 Weighted MRI Lesions [Months 0-3, 3-6, 6-9, 9-12, 12-18, 18-24, 24-36,36-48, and 48 to the end of the study (up to 4 years)]

   To ensure consistency, MRI scans were evaluated centrally at the Institute of Neurotherapeutics in Kyoto, Japan. After checking the scans for completeness and quality, all scans were analyzed by blinded readers (experienced neurologists). The number of new or newly enlarged T2 weighted MRI lesions were counted and recorded. New lesions were identified by comparing each lesion with previous scans. Lesions expanding through several slices were counted as only 1 lesion.

2. Aggregate Annualized Relapse Rate (ARR) Based on Confirmed Relapses [Months 0-6, 6-12, 12-24, 24-36, 36-48, and 48 to the end of the study (up to 4 years)]

   The ARR was defined as the total number of relapses for all patients in the treatment arm / total number of days in the study for all patients in the treatment arm for the specific period of time × 365.25. General definition of relapse: Appearance of a new neurological abnormality or worsening of previously stable or improving pre-existing neurological abnormality, separated by at least 30 days from the 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. A relapse was to be confirmed by a neurologist trained on the Expanded Disability Status Scale (EDSS). A relapse must be accompanied by an increase of at least half a step (0.5) on the EDSS or an increase of 1 point on 2 different Functional Systems (FS) of the EDSS or 2 points on 1 of the FS (excluding Bowel/Bladder or Cerebral FS).

3. Percentage of Patients Relapse-free at the End of the Study [Baseline to the end of the study (up to 4 years)]

   Patients who did not experience any relapses confirmed by a neurologist during the study were regarded as relapse-free patients.

4. Percentage of Patients Free From 3-month and 6-month Confirmed Disability Progression at Their Last Expanded Disability Status Scale (EDSS) Assessment [Baseline to the end of the study (up to 4 years)]

   Disability progression was measured by the EDSS score. A trained neurologist grades the multiple sclerosis (MS) disability of the patient on a scale of 0-5 (no to severe disability) in 8 Functional Systems (FS): Pyramidal, cerebellar, brainstem, sensory, bowel and bladder, visual, cerebral (or mental), and other. The EDSS score ranges from 0-10 (normal to dead) with higher scores indicating greater disability. A 3-month confirmed disability progression was defined as a 3-month sustained increase from baseline in the EDSS score, that is, every EDSS score obtained (scheduled or unscheduled) within 3-months after the first progression met the following progression criteria: One point (1) increase from baseline in patients with baseline EDSS score from 0 to 5.0; or half a point (0.5) increase in patients with baseline EDSS score of 5.5 or above. A 6-month confirmed disability progression was defined exactly the same except that the sustained progression had to last 6 months.

5. Change From Core Study Baseline in the Expanded Disability Status Scale (EDSS) Score [Baseline to Months 12, 24, 36, 48, and end of study (up to 4 years)]

   Disability progression was measured by the EDSS score. A trained neurologist grades the multiple sclerosis (MS) disability of the patient on a scale of 0-5 (no to severe disability) in 8 Functional Systems (FS): Pyramidal, cerebellar, brainstem, sensory, bowel and bladder, visual, cerebral (or mental), and other. The EDSS score ranges from 0-10 (normal to dead) with higher scores indicating greater disability. A 3-month confirmed disability progression was defined as a 3-month sustained increase from baseline in the EDSS score, that is, every EDSS score obtained (scheduled or unscheduled) within 3-months after the first progression met the following progression criteria: One point (1) increase from baseline in patients with baseline EDSS score from 0 to 5.0; or half a point (0.5) increase in patients with baseline EDSS score of 5.5 or above. A 6-month confirmed disability progression was defined exactly the same except that the sustained progression had to last 6 months.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients who completed 6 months of treatment with the study drug and the Month 6 visit in the core study NCT00537082.

• Females of childbearing potential who have a negative pregnancy test in the core study NCT00537082.

Exclusion Criteria:

• Patients who permanently discontinued study drug treatment prior to the Month 6 visit in the core study NCT00537082.

Other protocol-defined inclusion/exclusion criteria applied to the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Chiba		Japan	276-8524
2	Novartis Investigative Site	Ehime		Japan	791-0295
3	Novartis Investigative Site	Fukuoka		Japan	807-8555
4	Novartis Investigative Site	Gunma		Japan	371-8511
5	Novartis Investigative Site	Hyogo		Japan	650-0017
6	Novartis Investigative Site	Ibaraki		Japan	305-8576
7	Novartis Investigative Site	Kanagawa		Japan	259-1193
8	Novartis Investigative Site	Kyoto		Japan	604-8453
9	Novartis Investigative Site	Kyoto		Japan	616-8255
10	Novartis Investigative Site	Morioka		Japan	020-8505
11	Novartis Investigative Site	Niigata		Japan	951-8520
12	Novartis Investigative Site	Osaka		Japan	556-0016
13	Novartis Investigative Site	Osaka		Japan	589-8511
14	Novartis Investigative Site	Osaka		Japan
15	Novartis Investigative Site	Sapporo		Japan	060-8648
16	Novartis Investigative Site	Tochigi		Japan	329-0498
17	Novartis Investigative Site	Tokyo		Japan	113-8519
18	Novartis Investigative Site	Tokyo		Japan	145-0065
19	Novartis Investigative Site	Tokyo		Japan	162-8666
20	Novartis Investigative Site	Wakayama		Japan	641-8510

Sponsors and Collaborators

• Novartis
• Mitsubishi Tanabe Pharma Corporation

Investigators

• Principal Investigator: Novartis Pharmaceuticals, Japan, 81-3-3797-8748

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Novartis
• ClinicalTrials.gov Identifier: NCT00670449
• Other Study ID Numbers: CFTY720D1201E1
• First Posted: May 1, 2008
• Last Update Posted: Sep 4, 2013
• Last Verified: Jun 1, 2013

• Keywords provided by Novartis: FTY720; multiple sclerosis; MS
• Additional relevant MeSH terms: Multiple Sclerosis; Sclerosis; Fingolimod Hydrochloride

Study Results

Participant Flow

Arm/Group Title	Fingolimod 0.5 mg	Fingolimod 1.25 mg	Placebo-fingolimod 0.5 mg	Placebo-fingolimod 1.25 mg
Arm/Group Description	Patients who received fingolimod 0.5 orally once daily in the core study continued on the same dose in this extension study.	Patients who received fingolimod 1.25 mg orally once daily in the core study continued on the same dose in this extension study.	Patients who were randomized to placebo in the core study were re-randomized to either fingolimod 0.5 or 1.25 mg (1:1) orally once daily in this extension study.	Patients who were randomized to placebo in the core study were re-randomized to either fingolimod 0.5 or 1.25 mg (1:1) orally once daily in this extension study.
Period Title: Overall Study
STARTED	47	46	27	23
Switched to 0.5mg (Open Label)	45	41	23	17
COMPLETED	38	36	18	15
NOT COMPLETED	9	10	9	8

Baseline Characteristics

Arm/Group Title	Fingolimod 0.5 mg	Fingolimod 1.25 mg	Placebo-fingolimod 0.5 mg	Placebo-fingolimod 1.25 mg	Total
Arm/Group Description	Patients who received fingolimod 0.5 orally once daily in the core study continued on the same dose in this extension study.	Patients who received fingolimod 1.25 mg orally once daily in the core study continued on the same dose in this extension study.	Patients who were randomized to placebo in the core study were re-randomized to either fingolimod 0.5 or 1.25 mg (1:1) orally once daily in this extension study.	Patients who were randomized to placebo in the core study were re-randomized to either fingolimod 0.5 or 1.25 mg (1:1) orally once daily in this extension study.	Total of all reporting groups
Overall Participants	47	46	27	23	143
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	34.9 (8.95)	35.7 (8.81)	34.2 (9.08)	35.5 (8.44)	35.1 (8.78)
Sex: Female, Male (Count of Participants)
Female	33 70.2%	31 67.4%	19 70.4%	14 60.9%	97 67.8%
Male	14 29.8%	15 32.6%	8 29.6%	9 39.1%	46 32.2%

Outcome Measures

1. Primary Outcome

Title	Percentage of Patients Free of Gd-enhanced T1 Weighted Magnetic Resonance Imaging (MRI) Lesions
Description	To ensure consistency, MRI scans were evaluated centrally at the Institute of Neurotherapeutics in Kyoto, Japan. After checking the scans for completeness and quality, all scans were analyzed by blinded readers (experienced neurologists). The number of Gd-enhanced T1 weighted MRI lesions were counted and recorded. Lesions expanding through several slices were counted as only 1 lesion.
Time Frame	Months 6, 9, 12, 18, 24, 36, and 48

Outcome Measure Data

Analysis Population Description

Core full analysis set (FAS): All patients who were randomized in the core study and received at least 1 dose of core study drug. The study became open-label with all patients receiving FTY720 0.5 mg/day (by 22-Feb- 2010). (approximately 22 months before study completion)

Arm/Group Title	Fingolimod 0.5 mg	Fingolimod 1.25 mg	Placebo-fingolimod
Arm/Group Description	Patients who received fingolimod 0.5 orally once daily in the core study continued on the same dose in this extension study.	Patients who received fingolimod 1.25 mg orally once daily in the core study continued on the same dose in this extension study.	Patients randomized to placebo in the Core study. These patients were either subsequently re-randomized to FTY720 (either 1.25 mg or 0.5 mg) in the Extension study, or did not enter the Extension study.
Measure Participants	57	54	57
Month 6 (N=44, 48, 50)	88.6	97.9	58.0
Month 9 (N=44, 39, 41)	90.9	94.9	92.7
Month 12 (N=44, 42, 36)	97.7	97.6	88.9
Month 18 (N=42, 40, 37)	92.9	92.5	94.6
Month 24 (N=38, 39, 33)	94.7	94.9	90.9
Month 36 (N=25, 21, 22)	92.0	85.7	90.9
Month 48 (N=3, 4, 1)	100.0	75.0	100.0

2. Secondary Outcome

Title	Percentage of Patients Free of New or Newly Enlarged T2 Weighted MRI Lesions
Description	To ensure consistency, MRI scans were evaluated centrally at the Institute of Neurotherapeutics in Kyoto, Japan. After checking the scans for completeness and quality, all scans were analyzed by blinded readers (experienced neurologists). The number of new or newly enlarged T2 weighted MRI lesions were counted and recorded. New lesions were identified by comparing each lesion with previous scans. Lesions expanding through several slices were counted as only 1 lesion.
Time Frame	Months 0-3, 3-6, 6-9, 9-12, 12-18, 18-24, 24-36,36-48, and 48 to the end of the study (up to 4 years)

Outcome Measure Data

Analysis Population Description

Core full analysis set(FAS): All patients who were randomized in the core study and received at least 1 dose of core study drug. Study became open-label with all patients receiving FTY720 0.5 mg/day. The study became open-label with all patients receiving FTY720 0.5 mg/day (by 22-Feb-2010). (approximately 22 months before study completion)

Arm/Group Title	Fingolimod 0.5 mg	Fingolimod 1.25 mg	Placebo-fingolimod
Arm/Group Description	Patients who received fingolimod 0.5 orally once daily in the core study continued on the same dose in this extension study.	Patients who received fingolimod 1.25 mg orally once daily in the core study continued on the same dose in this extension study.	Patients randomized to placebo in the Core study. These patients were either subsequently re-randomized to FTY720 (either 1.25 mg or 0.5 mg) in the Extension study, or did not enter the Extension study.
Measure Participants	57	54	57
Month 0 to 3 (N=49, 50, 51)	69.4	60.0	45.1
Month 3 to 6 (N=43, 47, 48)	86.0	91.5	43.8
Month 6 to 9 (N=44, 39, 40)	88.6	92.3	70.0
Month 9 to 12 (N=44, 42, 35)	93.2	95.2	85.7
Month 12 to 18 (N=43, 40, 37)	88.4	90.0	91.9
Month 18 to 24 (N=39, 39, 33)	94.9	92.3	87.9
Month 24 to 36 (N=25, 21, 22)	92.0	90.5	90.9
Month 36 to 48 (N=3, 4, 1)	100.0	100.0	100.0
Month 48 to end of study (N=3, 3, 1)	100.0	100.0	100.0

3. Secondary Outcome

Title	Aggregate Annualized Relapse Rate (ARR) Based on Confirmed Relapses
Description	The ARR was defined as the total number of relapses for all patients in the treatment arm / total number of days in the study for all patients in the treatment arm for the specific period of time × 365.25. General definition of relapse: Appearance of a new neurological abnormality or worsening of previously stable or improving pre-existing neurological abnormality, separated by at least 30 days from the 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. A relapse was to be confirmed by a neurologist trained on the Expanded Disability Status Scale (EDSS). A relapse must be accompanied by an increase of at least half a step (0.5) on the EDSS or an increase of 1 point on 2 different Functional Systems (FS) of the EDSS or 2 points on 1 of the FS (excluding Bowel/Bladder or Cerebral FS).
Time Frame	Months 0-6, 6-12, 12-24, 24-36, 36-48, and 48 to the end of the study (up to 4 years)

Outcome Measure Data

Analysis Population Description

Core full analysis set (FAS): All patients who were randomized in the core study and received at least 1 dose of core study drug. The study became open-label with all patients receiving FTY720 0.5 mg/day (by 22-Feb- 2010). (approximately 22 months before study completion)

Arm/Group Title	Fingolimod 0.5 mg	Fingolimod 1.25 mg	Placebo-fingolimod
Arm/Group Description	Patients who received fingolimod 0.5 orally once daily in the core study continued on the same dose in this extension study.	Patients who received fingolimod 1.25 mg orally once daily in the core study continued on the same dose in this extension study.	Patients randomized to placebo in the Core study. These patients were either subsequently re-randomized to FTY720 (either 1.25 mg or 0.5 mg) in the Extension study, or did not enter the Extension study.
Measure Participants	57	54	57
Month 0 to 6 (N=57, 54, 57)	0.539	0.404	1.131
Month 6 to 12 (N=47, 46, 50)	0.227	0.284	0.232
Month 12 to 24 (N=44, 43, 39)	0.166	0.223	0.222
Month 24 to 36 (N=41, 40, 34)	0.191	0.058	0.162
Month 36 to 48 (N=28, 23, 23)	0.164	0.075	0.309
Month 48 to end of study (N=8, 6, 3)	0.000	0.000	0.000

4. Secondary Outcome

Title	Percentage of Patients Relapse-free at the End of the Study
Description	Patients who did not experience any relapses confirmed by a neurologist during the study were regarded as relapse-free patients.
Time Frame	Baseline to the end of the study (up to 4 years)

Outcome Measure Data

Analysis Population Description

Core full analysis set (FAS): All patients who were randomized in the core study and received at least 1 dose of core study drug. The study became open-label with all patients receiving FTY720 0.5 mg/day (by 22-Feb- 2010).(approximately 22 months before study completion)

Arm/Group Title	Fingolimod 0.5 mg	Fingolimod 1.25 mg	Placebo-fingolimod
Arm/Group Description	Patients who received fingolimod 0.5 orally once daily in the core study continued on the same dose in this extension study.	Patients who received fingolimod 1.25 mg orally once daily in the core study continued on the same dose in this extension study.	Patients randomized to placebo in the Core study. These patients were either subsequently re-randomized to FTY720 (either 1.25 mg or 0.5 mg) in the Extension study, or did not enter the Extension study.
Measure Participants	57	54	57
Number (95% Confidence Interval) [Percentage of patients]	45.2	62.1	48.3

5. Secondary Outcome

Title	Percentage of Patients Free From 3-month and 6-month Confirmed Disability Progression at Their Last Expanded Disability Status Scale (EDSS) Assessment
Description	Disability progression was measured by the EDSS score. A trained neurologist grades the multiple sclerosis (MS) disability of the patient on a scale of 0-5 (no to severe disability) in 8 Functional Systems (FS): Pyramidal, cerebellar, brainstem, sensory, bowel and bladder, visual, cerebral (or mental), and other. The EDSS score ranges from 0-10 (normal to dead) with higher scores indicating greater disability. A 3-month confirmed disability progression was defined as a 3-month sustained increase from baseline in the EDSS score, that is, every EDSS score obtained (scheduled or unscheduled) within 3-months after the first progression met the following progression criteria: One point (1) increase from baseline in patients with baseline EDSS score from 0 to 5.0; or half a point (0.5) increase in patients with baseline EDSS score of 5.5 or above. A 6-month confirmed disability progression was defined exactly the same except that the sustained progression had to last 6 months.
Time Frame	Baseline to the end of the study (up to 4 years)

Outcome Measure Data

Analysis Population Description

Core full analysis set (FAS): All patients who were randomized in the core study and received at least 1 dose of core study drug. The study became open-label with all patients receiving FTY720 0.5 mg/day (by 22-Feb- 2010). (approximately 22 months before study completion)

Arm/Group Title	Fingolimod 0.5 mg	Fingolimod 1.25 mg	Placebo-fingolimod
Arm/Group Description	Patients who received fingolimod 0.5 orally once daily in the core study continued on the same dose in this extension study.	Patients who received fingolimod 1.25 mg orally once daily in the core study continued on the same dose in this extension study.	Patients randomized to placebo in the Core study. These patients were either subsequently re-randomized to FTY720 (either 1.25 mg or 0.5 mg) in the Extension study, or did not enter the Extension study.
Measure Participants	57	54	57
Free from 3-month confirmed disability progression	74.3	82.4	90.6
Free from 6-month confirmed disability progression	87.1	90.7	92.3

6. Secondary Outcome

Title	Change From Core Study Baseline in the Expanded Disability Status Scale (EDSS) Score
Description	Disability progression was measured by the EDSS score. A trained neurologist grades the multiple sclerosis (MS) disability of the patient on a scale of 0-5 (no to severe disability) in 8 Functional Systems (FS): Pyramidal, cerebellar, brainstem, sensory, bowel and bladder, visual, cerebral (or mental), and other. The EDSS score ranges from 0-10 (normal to dead) with higher scores indicating greater disability. A 3-month confirmed disability progression was defined as a 3-month sustained increase from baseline in the EDSS score, that is, every EDSS score obtained (scheduled or unscheduled) within 3-months after the first progression met the following progression criteria: One point (1) increase from baseline in patients with baseline EDSS score from 0 to 5.0; or half a point (0.5) increase in patients with baseline EDSS score of 5.5 or above. A 6-month confirmed disability progression was defined exactly the same except that the sustained progression had to last 6 months.
Time Frame	Baseline to Months 12, 24, 36, 48, and end of study (up to 4 years)

Outcome Measure Data

Analysis Population Description

Core full analysis set (FAS): All patients who were randomized in the core study and received at least 1 dose of core study drug. • The study became open-label with all patients receiving FTY720 0.5 mg/day (by 22-Feb- 2010). (approximately 22 months before study completion)

Arm/Group Title	Fingolimod 0.5 mg	Fingolimod 1.25 mg	Placebo-fingolimod
Arm/Group Description	Patients who received fingolimod 0.5 orally once daily in the core study continued on the same dose in this extension study.	Patients who received fingolimod 1.25 mg orally once daily in the core study continued on the same dose in this extension study.	Patients randomized to placebo in the Core study. These patients were either subsequently re-randomized to FTY720 (either 1.25 mg or 0.5 mg) in the Extension study, or did not enter the Extension study.
Measure Participants	57	54	57
Month 12 (N=45, 43, 40)	-0.02 (0.464)	-0.02 (0.831)	-0.23 (0.800)
Month 24 (N=42, 40, 35)	-0.12 (0.723)	-0.06 (1.033)	-0.21 (0.789)
Month 36 (N=25, 21, 23)	0.16 (1.441)	-0.07 (0.912)	-0.37 (0.678)
Month 48 (N=3, 4, 1)	1.17 (0.764)	-0.63 (0.946)	0.00 (0.000)
End of study (N=37, 36, 32)	0.00 (1.225)	-0.17 (0.902)	-0.31 (0.830)

Adverse Events

Adverse Event Reporting Description	Extension safety population: All patients who received at least 1 dose of study drug in the extension study.
Arm/Group Title	Fingolimod 1.25 mg		Fingolimod 0.5 mg		Placebo-fingolimod 1.25 mg		Placebo-fingolimod 0.5 mg
Arm/Group Description	Patients who received fingolimod 1.25 mg orally once daily in the core study continued on the same dose in this extension study.		Patients who received fingolimod 0.5 orally once daily in the core study continued on the same dose in this extension study.		Patients who were randomized to placebo in the core study were re-randomized to either fingolimod 0.5 or 1.25 mg (1:1) orally once daily in this extension study.		Patients who were randomized to placebo in the core study were re-randomized to either fingolimod 0.5 or 1.25 mg (1:1) orally once daily in this extension study.
All Cause Mortality
	Fingolimod 1.25 mg		Fingolimod 0.5 mg		Placebo-fingolimod 1.25 mg		Placebo-fingolimod 0.5 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Fingolimod 1.25 mg		Fingolimod 0.5 mg		Placebo-fingolimod 1.25 mg		Placebo-fingolimod 0.5 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/46 (10.9%)		8/47 (17%)		5/23 (21.7%)		1/27 (3.7%)
Cardiac disorders
Bradycardia	0/46 (0%)		0/47 (0%)		2/23 (8.7%)		0/27 (0%)
Eye disorders
Cataract	1/46 (2.2%)		0/47 (0%)		0/23 (0%)		0/27 (0%)
Gastrointestinal disorders
Tooth impacted	1/46 (2.2%)		0/47 (0%)		0/23 (0%)		0/27 (0%)
Immune system disorders
Food allergy	0/46 (0%)		1/47 (2.1%)		0/23 (0%)		0/27 (0%)
Infections and infestations
Appendicitis	1/46 (2.2%)		0/47 (0%)		0/23 (0%)		0/27 (0%)
Urinary tract infection	1/46 (2.2%)		0/47 (0%)		0/23 (0%)		0/27 (0%)
Injury, poisoning and procedural complications
Eyeball rupture	1/46 (2.2%)		0/47 (0%)		0/23 (0%)		0/27 (0%)
Hip fracture	0/46 (0%)		1/47 (2.1%)		0/23 (0%)		0/27 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer	0/46 (0%)		1/47 (2.1%)		0/23 (0%)		0/27 (0%)
Central nervous system lymphoma	0/46 (0%)		1/47 (2.1%)		0/23 (0%)		0/27 (0%)
Nervous system disorders
Convulsion	0/46 (0%)		1/47 (2.1%)		0/23 (0%)		0/27 (0%)
Leukoencephalopathy	0/46 (0%)		0/47 (0%)		1/23 (4.3%)		0/27 (0%)
Multiple sclerosis relapse	0/46 (0%)		1/47 (2.1%)		0/23 (0%)		0/27 (0%)
Myoclonus	0/46 (0%)		1/47 (2.1%)		0/23 (0%)		0/27 (0%)
Neuromyelitis optica	0/46 (0%)		0/47 (0%)		0/23 (0%)		1/27 (3.7%)
Radiculitis	0/46 (0%)		0/47 (0%)		1/23 (4.3%)		0/27 (0%)
Status epilepticus	1/46 (2.2%)		0/47 (0%)		0/23 (0%)		0/27 (0%)
Respiratory, thoracic and mediastinal disorders
Haemothorax	0/46 (0%)		1/47 (2.1%)		0/23 (0%)		0/27 (0%)
Pneumonia aspiration	1/46 (2.2%)		0/47 (0%)		0/23 (0%)		0/27 (0%)
Surgical and medical procedures
Abortion induced	1/46 (2.2%)		0/47 (0%)		1/23 (4.3%)		0/27 (0%)
Other (Not Including Serious) Adverse Events
	Fingolimod 1.25 mg		Fingolimod 0.5 mg		Placebo-fingolimod 1.25 mg		Placebo-fingolimod 0.5 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	43/46 (93.5%)		42/47 (89.4%)		21/23 (91.3%)		25/27 (92.6%)
Blood and lymphatic system disorders
Leukopenia	5/46 (10.9%)		2/47 (4.3%)		1/23 (4.3%)		4/27 (14.8%)
Lymphopenia	8/46 (17.4%)		6/47 (12.8%)		3/23 (13%)		2/27 (7.4%)
Cardiac disorders
Atrioventricular block second degree	0/46 (0%)		0/47 (0%)		3/23 (13%)		0/27 (0%)
Eye disorders
Cataract	2/46 (4.3%)		3/47 (6.4%)		1/23 (4.3%)		2/27 (7.4%)
Dry eye	0/46 (0%)		3/47 (6.4%)		0/23 (0%)		1/27 (3.7%)
Gastrointestinal disorders
Abdominal pain upper	2/46 (4.3%)		3/47 (6.4%)		0/23 (0%)		2/27 (7.4%)
Constipation	2/46 (4.3%)		5/47 (10.6%)		0/23 (0%)		1/27 (3.7%)
Dental caries	4/46 (8.7%)		3/47 (6.4%)		2/23 (8.7%)		2/27 (7.4%)
Diarrhoea	6/46 (13%)		3/47 (6.4%)		2/23 (8.7%)		1/27 (3.7%)
Gastric ulcer	1/46 (2.2%)		1/47 (2.1%)		0/23 (0%)		2/27 (7.4%)
Gastritis	2/46 (4.3%)		3/47 (6.4%)		0/23 (0%)		1/27 (3.7%)
Gingivitis	3/46 (6.5%)		0/47 (0%)		0/23 (0%)		1/27 (3.7%)
Haemorrhoids	3/46 (6.5%)		0/47 (0%)		0/23 (0%)		1/27 (3.7%)
Nausea	3/46 (6.5%)		3/47 (6.4%)		0/23 (0%)		0/27 (0%)
Stomatitis	6/46 (13%)		4/47 (8.5%)		1/23 (4.3%)		4/27 (14.8%)
Immune system disorders
Seasonal allergy	1/46 (2.2%)		1/47 (2.1%)		2/23 (8.7%)		0/27 (0%)
Infections and infestations
Cystitis	7/46 (15.2%)		3/47 (6.4%)		1/23 (4.3%)		2/27 (7.4%)
Folliculitis	2/46 (4.3%)		0/47 (0%)		0/23 (0%)		2/27 (7.4%)
Herpes zoster	1/46 (2.2%)		1/47 (2.1%)		2/23 (8.7%)		1/27 (3.7%)
Influenza	6/46 (13%)		3/47 (6.4%)		3/23 (13%)		2/27 (7.4%)
Nasopharyngitis	28/46 (60.9%)		29/47 (61.7%)		12/23 (52.2%)		15/27 (55.6%)
Onychomycosis	1/46 (2.2%)		1/47 (2.1%)		0/23 (0%)		2/27 (7.4%)
Oral herpes	0/46 (0%)		0/47 (0%)		2/23 (8.7%)		0/27 (0%)
Pharyngitis	4/46 (8.7%)		5/47 (10.6%)		2/23 (8.7%)		1/27 (3.7%)
Sinusitis	3/46 (6.5%)		0/47 (0%)		0/23 (0%)		1/27 (3.7%)
Tinea pedis	1/46 (2.2%)		3/47 (6.4%)		1/23 (4.3%)		2/27 (7.4%)
Injury, poisoning and procedural complications
Contusion	2/46 (4.3%)		2/47 (4.3%)		0/23 (0%)		2/27 (7.4%)
Investigations
Alanine aminotransferase increased	1/46 (2.2%)		0/47 (0%)		0/23 (0%)		2/27 (7.4%)
Blood triglycerides increased	0/46 (0%)		1/47 (2.1%)		0/23 (0%)		2/27 (7.4%)
Gamma-glutamyltransferase increased	0/46 (0%)		1/47 (2.1%)		2/23 (8.7%)		1/27 (3.7%)
Liver function test abnormal	8/46 (17.4%)		6/47 (12.8%)		9/23 (39.1%)		7/27 (25.9%)
Lymphocyte count decreased	2/46 (4.3%)		3/47 (6.4%)		2/23 (8.7%)		3/27 (11.1%)
White blood cell count decreased	3/46 (6.5%)		2/47 (4.3%)		2/23 (8.7%)		1/27 (3.7%)
Metabolism and nutrition disorders
Hyperlipidaemia	5/46 (10.9%)		2/47 (4.3%)		0/23 (0%)		2/27 (7.4%)
Musculoskeletal and connective tissue disorders
Arthralgia	4/46 (8.7%)		0/47 (0%)		0/23 (0%)		0/27 (0%)
Back pain	2/46 (4.3%)		3/47 (6.4%)		0/23 (0%)		0/27 (0%)
Myalgia	1/46 (2.2%)		3/47 (6.4%)		0/23 (0%)		0/27 (0%)
Neck pain	1/46 (2.2%)		3/47 (6.4%)		0/23 (0%)		0/27 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Skin papilloma	0/46 (0%)		6/47 (12.8%)		0/23 (0%)		0/27 (0%)
Nervous system disorders
Dizziness	1/46 (2.2%)		4/47 (8.5%)		0/23 (0%)		0/27 (0%)
Headache	3/46 (6.5%)		8/47 (17%)		3/23 (13%)		1/27 (3.7%)
Psychiatric disorders
Insomnia	2/46 (4.3%)		4/47 (8.5%)		1/23 (4.3%)		2/27 (7.4%)
Reproductive system and breast disorders
Dysmenorrhoea	2/46 (4.3%)		3/47 (6.4%)		0/23 (0%)		0/27 (0%)
Respiratory, thoracic and mediastinal disorders
Rhinitis allergic	3/46 (6.5%)		3/47 (6.4%)		1/23 (4.3%)		0/27 (0%)
Skin and subcutaneous tissue disorders
Dry skin	0/46 (0%)		3/47 (6.4%)		0/23 (0%)		1/27 (3.7%)
Eczema	4/46 (8.7%)		3/47 (6.4%)		2/23 (8.7%)		1/27 (3.7%)
Erythema	3/46 (6.5%)		0/47 (0%)		0/23 (0%)		0/27 (0%)
Hyperkeratosis	0/46 (0%)		0/47 (0%)		0/23 (0%)		2/27 (7.4%)
Rash	0/46 (0%)		1/47 (2.1%)		4/23 (17.4%)		3/27 (11.1%)
Urticaria	0/46 (0%)		4/47 (8.5%)		1/23 (4.3%)		0/27 (0%)
Xeroderma	0/46 (0%)		1/47 (2.1%)		1/23 (4.3%)		2/27 (7.4%)
Vascular disorders
Hypertension	1/46 (2.2%)		3/47 (6.4%)		1/23 (4.3%)		0/27 (0%)

Limitations/Caveats

[Not Specified]

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Principal Investigators are NOT employed by the organization sponsoring the study.

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.