ASSESS: MS Study Evaluating Safety and Efficacy of Two Doses of Fingolimod Versus Copaxone

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01633112
• Collaborator: (none)
• Enrollment: 1,064
• Locations: 130
• Arms: 3
• Actual Duration (Months): 68.7
• Patients Per Site: 8.2
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study was to demonstrate that at least one dose (0.5 mg followed by 0.25 mg) of fingolimod is superior to glatiramer acetate 20 mg SC in reducing the ARR up to 12 months in patients with relapsing-remitting MS

Condition or Disease	Intervention/Treatment	Phase
Relapsing-remitting Multiple Sclerosis (RRMS)	Drug: fingolimod; Drug: glatiramer acetate	Phase 3

Detailed Description

This was a multicenter, randomized, rater- and dose-blinded, study to compare the efficacy and safety of 0.25 mg and 0.5 mg of fingolimod with glatimer acetate 20 mg s.c. in patients with RRMS.

This study consisted of 3 periods:

• Screening Period: up to 45 days for all patients

• Treatment Period: 12 months of glatiramer acetate 20 mg, fingolimod 0.25 mg, or fingolimod 0.5 mg

• Follow-up occurred 3 months (12 weeks) after the last dose of study drug for all patients The informed consent form was signed prior to any study related activities at the screening visit. Randomization to either treatment group was preformed at visit 1 after a diligent check of applicable in- and exclusion criteria in a 1:1:1 ratio (changed to 5:3:2 after implementation of Amendment 2 in 2015).

Treatment groups:

• fingolimod 0.5 mg/day orally for up to 12 months

• fingolimod 0.25 mg/day orally for up to 12 months

• glatiramer acetate 20 mg/day subcutaneously for up to 12 months

Study Design

• Study Type: Interventional
• Actual Enrollment: 1064 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Outcomes Assessor)
• Masking Description: Fingolimod patients were dose blind.
• Primary Purpose: Treatment
• Official Title: A 12-month, Randomized, Rater- and Dose-blinded Study to Compare the Efficacy and Safety of Fingolimod 0.25 mg and 0.5 mg Administered Orally Once Daily With Glatiramer Acetate 20 mg Administered Subcutaneously Once Daily in Patients With Relapsing-remitting Multiple Sclerosis
• Actual Study Start Date: Aug 9, 2012
• Actual Primary Completion Date: Apr 30, 2018
• Actual Study Completion Date: Apr 30, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: fingolimod 0.5 mg orally once daily	Drug: fingolimod; capsule; Other Names: FTY720, fingolimod hydrochloride, Gilenya
Experimental: fingolimod 0.25mg orally once daily	Drug: fingolimod; capsule; Other Names: FTY720, fingolimod hydrochloride, Gilenya
Active Comparator: glatiramer acetate 20 mg subcutaneous once daily	Drug: glatiramer acetate; subcutaneous injection; Other Names: Copaxone, Glatopa

Outcome Measures

Primary Outcome Measures

1. Confirmed Annualized Relapse Rate [up to 12 months]

   Annualized relapse rate (ARR) was defined as the average number of confirmed relapses per year (i.e., the total number of confirmed relapses divided by the total days in the study multiplied by 365.25). The number of relapses included all the confirmed relapses experienced during the study from first dose to end of study.

Secondary Outcome Measures

1. New or Newly Enlarging T2 Lesions [At 12 months/end of study]

   Inflammatory activity based on MRI measurement of new/newly enlarged T2 lesion count.

2. Number of Participants Free of New/Newly Enlarged T2 Lesions [At 12 months/end of study]

   Inflammatory activity based on MRI measurement of new/newly enlarged T2 lesion count.

3. Change From Baseline in T2 Lesion Volume [Baseline, 12 months/end of study]

   Inflammatory activity based on MRI measurement of new/newly enlarged T2 lesion volume

4. Gd Enhancing T1 Lesion Count [At 12 months/end of study]

   Inflammatory activity based on MRI measurement of Gd enhancing T1 lesion count

5. Gd Enhancing T1 Lesion Volume [Baseline, 12 months/end of study]

   Inflammatory activity based on MRI measurement of Gd enhancing T1 lesion count

6. Percentage of Patients Free of New T1 Hypointense Lesions [12 months]

   Based on MRI measures of new T1 hypointense lesions

7. Change From Baseline in TSQM Scales [6 months, 12 months/end of study]

   Treatment Satisfaction Questionnaire for Medication (TSQM) was developed and validated as a general measure for treatment satisfaction. Each scale score was calculated by summing individual items and then transformed to a 0-100 scale. Higher summary scores indicate better satisfaction with study drug.

8. Percent Brain Volume Change From Baseline [Baseline, 12 months, end of study]

   Using a Central MRI vendor to ensure calibrated MRI scanning equipment across all sites, MRI scans were performed on subjects following the established parameters and transferred to the central vendor for review of quality and assessment/evaluation.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion criteria:

• Written informed consent must be obtained before any assessment is performed

• Male and female patients 18 to 65 years of age, inclusive.

• Patients with RRMS, as defined by 2010 revised McDonald criteria.

• Patients must be neurologically stable with no onset of relapse within 30 days of randomization

• Patients with at least 1 documented relapse during the previous year or 2 documented relapses during the previous 2 years before randomization.

• Patients with an EDSS score of 0 to 6, inclusive, at Screening. A score of 6.0 indicates unilateral assistance (cane or crutch) required to walk at least 100 meters with or without resting.

Exclusion criteria:

• Patients with a history of malignancy of any organ system (other than cutaneous basal cell carcinoma) in the last 5 years that do not have confirmation of absence of a malignancy prior to randomization

• Patients with an active chronic disease (or stable but treated with immune therapy) of the immune system other than MS (e.g., rheumatoid arthritis, scleroderma, Sjogren's syndrome, Crohn's disease, ulcerative colitis) or with a known immunodeficiency syndrome (HIV-antibody positive, AIDS, hereditary immune deficiency, drug-induced immune deficiency).

• Patients who have been treated with:

• High-dose intravenous (IV) immunoglobulin (Ig) within 4 weeks before randomization

• Immunosuppressive/chemotherapeutic medications (e.g., azathioprine, cyclophosphamide, methotrexate) within 6 months before randomization

• Natalizumab within 2 months before randomization

• Previous treatment with lymphocyte-depleting therapies (e.g., rituximab, alemtuzumab, ofatumumab, ocrelizumab, or cladribine) within 1 year before randomization Previous treatment with mitoxantrone within 6 months before randomization

• Use of teriflunomide within 3.5 months prior to randomization, except if active washout (with either cholestyramine or activated charcoal) was done. In that case, plasma levels are required to be measured and be below 0.02 mg/L before randomization.

No washout period is necessary for patients treated with dimethyl fumarate, interferon (IFN) beta, or glatiramer acetate.

Patients being treated with dimethyl fumarate, glatiramer acetate, or IFN beta at the Screening visit can continue drug intake up to the day before Day 1 of this study (i.e., there is no need for a washout period).

• Patients who have been treated with systemic corticosteroids or adrenocorticotropic hormones in the past 30 days prior to the screening magnetic resonance imaging (MRI) procedure.

• Patients with uncontrolled diabetes mellitus (glycosylated hemoglobin >9%) or with diabetic neuropathy.

• Patients with a diagnosis of macular edema during Screening (patients with a history of macular edema will be allowed to enter the study provided that they do not have macular edema at Screening).

• Patients with severe active bacterial, viral, or fungal infections.

• Patients without acceptable evidence of immunity to varicella zoster virus (VZV) at randomization.

• Patients who have received any live or live-attenuated vaccines (including VZV, herpes simplex, or measles) within 1 month before randomization.

• Patients who have received total lymphoid irradiation or bone marrow transplantation.

• Patients with any unstable medical/psychiatric condition, as assessed by the primary treating physician at each site.

• Patients who in the last 6 months experienced any of the following cardiovascular conditions or findings in the screening electrocardiogram (ECG): myocardial infarction, unstable angina, stroke, transient ischemic attack or decompensated heart failure requiring hospitalization or Class III/IV heart failure.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Cullman	Alabama	United States	35058
2	Novartis Investigative Site	Phoenix	Arizona	United States	85004
3	Novartis Investigative Site	Phoenix	Arizona	United States	85013
4	Novartis Investigative Site	Phoenix	Arizona	United States	85018
5	Novartis Investigative Site	Tucson	Arizona	United States	85741
6	Novartis Investigative Site	Los Angeles	California	United States	90089
7	Novartis Investigative Site	Sacramento	California	United States	95817
8	Novartis Investigative Site	Aurora	Colorado	United States	80045
9	Novartis Investigative Site	Boulder	Colorado	United States	80304
10	Novartis Investigative Site	Denver	Colorado	United States	80220
11	Novartis Investigative Site	Fort Collins	Colorado	United States	80528
12	Novartis Investigative Site	Loveland	Colorado	United States	80538
13	Novartis Investigative Site	Fairfield	Connecticut	United States	06824
14	Novartis Investigative Site	Newark	Delaware	United States	19713
15	Novartis Investigative Site	Washington	District of Columbia	United States	20007
16	Novartis Investigative Site	Jacksonville	Florida	United States	32209
17	Novartis Investigative Site	Maitland	Florida	United States	32751
18	Novartis Investigative Site	Naples	Florida	United States	34119
19	Novartis Investigative Site	New Port Richey	Florida	United States	34653
20	Novartis Investigative Site	Orlando	Florida	United States	32806
21	Novartis Investigative Site	Ormond Beach	Florida	United States	32174
22	Novartis Investigative Site	Pompano Beach	Florida	United States	33060
23	Novartis Investigative Site	Ponte Vedra Beach	Florida	United States	32082-4627
24	Novartis Investigative Site	Port Charlotte	Florida	United States	33952
25	Novartis Investigative Site	Sarasota	Florida	United States	34243
26	Novartis Investigative Site	Tallahassee	Florida	United States	32308
27	Novartis Investigative Site	Tampa	Florida	United States	33609
28	Novartis Investigative Site	Vero Beach	Florida	United States	32960
29	Novartis Investigative Site	West Palm Beach	Florida	United States	33407
30	Novartis Investigative Site	Atlanta	Georgia	United States	30327
31	Novartis Investigative Site	Elk Grove Village	Illinois	United States	60007
32	Novartis Investigative Site	Evanston	Illinois	United States	60201
33	Novartis Investigative Site	Flossmoor	Illinois	United States	60422
34	Novartis Investigative Site	Northbrook	Illinois	United States	60062
35	Novartis Investigative Site	Indianapolis	Indiana	United States	46202
36	Novartis Investigative Site	Indianapolis	Indiana	United States	46256
37	Novartis Investigative Site	West Des Moines	Iowa	United States	50314
38	Novartis Investigative Site	Kansas City	Kansas	United States	66160
39	Novartis Investigative Site	Lenexa	Kansas	United States	66212
40	Novartis Investigative Site	Louisville	Kentucky	United States	40207
41	Novartis Investigative Site	Hammond	Louisiana	United States	70403
42	Novartis Investigative Site	New Orleans	Louisiana	United States	70121
43	Novartis Investigative Site	Baltimore	Maryland	United States	21201
44	Novartis Investigative Site	Boston	Massachusetts	United States	02215
45	Novartis Investigative Site	Springfield	Massachusetts	United States	01104
46	Novartis Investigative Site	Detroit	Michigan	United States	48201
47	Novartis Investigative Site	Detroit	Michigan	United States	48202
48	Novartis Investigative Site	Farmington Hills	Michigan	United States	48334
49	Novartis Investigative Site	Grand Rapids	Michigan	United States	49503
50	Novartis Investigative Site	Traverse City	Michigan	United States	49684-2340
51	Novartis Investigative Site	Kansas City	Missouri	United States	64111
52	Novartis Investigative Site	Saint Louis	Missouri	United States	63104
53	Novartis Investigative Site	Saint Louis	Missouri	United States	63131
54	Novartis Investigative Site	Saint Louis	Missouri	United States	63141
55	Novartis Investigative Site	Great Falls	Montana	United States	59405
56	Novartis Investigative Site	Las Vegas	Nevada	United States	89106
57	Novartis Investigative Site	Freehold	New Jersey	United States	07728
58	Novartis Investigative Site	Newark	New Jersey	United States	07103
59	Novartis Investigative Site	Teaneck	New Jersey	United States	07666
60	Novartis Investigative Site	Albuquerque	New Mexico	United States	87131
61	Novartis Investigative Site	Albany	New York	United States	12208
62	Novartis Investigative Site	Amherst	New York	United States	14226
63	Novartis Investigative Site	Buffalo	New York	United States	14203
64	Novartis Investigative Site	Patchogue	New York	United States	11772
65	Novartis Investigative Site	Rochester	New York	United States	14642
66	Novartis Investigative Site	Stony Brook	New York	United States	11794
67	Novartis Investigative Site	Syracuse	New York	United States	13210
68	Novartis Investigative Site	Chapel Hill	North Carolina	United States	27599-9500
69	Novartis Investigative Site	Charlotte	North Carolina	United States	28204
70	Novartis Investigative Site	Winston-Salem	North Carolina	United States	27157
71	Novartis Investigative Site	Akron	Ohio	United States	44320
72	Novartis Investigative Site	Bellevue	Ohio	United States	44811
73	Novartis Investigative Site	Columbus	Ohio	United States	43210
74	Novartis Investigative Site	Columbus	Ohio	United States	43221
75	Novartis Investigative Site	Dayton	Ohio	United States	45408
76	Novartis Investigative Site	Toledo	Ohio	United States	43614
77	Novartis Investigative Site	Oklahoma City	Oklahoma	United States	73104
78	Novartis Investigative Site	Oklahoma City	Oklahoma	United States	73112
79	Novartis Investigative Site	Tulsa	Oklahoma	United States	74137
80	Novartis Investigative Site	Portland	Oregon	United States	97225
81	Novartis Investigative Site	Philadelphia	Pennsylvania	United States	19141
82	Novartis Investigative Site	Spartanburg	South Carolina	United States	29302
83	Novartis Investigative Site	Cordova	Tennessee	United States	38018
84	Novartis Investigative Site	Knoxville	Tennessee	United States	37934
85	Novartis Investigative Site	Nashville	Tennessee	United States	37204
86	Novartis Investigative Site	Nashville	Tennessee	United States	37205
87	Novartis Investigative Site	Dallas	Texas	United States	75214
88	Novartis Investigative Site	Houston	Texas	United States	77030
89	Novartis Investigative Site	Round Rock	Texas	United States	78681
90	Novartis Investigative Site	San Antonio	Texas	United States	78258
91	Novartis Investigative Site	Sherman	Texas	United States	75092
92	Novartis Investigative Site	Salt Lake City	Utah	United States	84103
93	Novartis Investigative Site	Alexandria	Virginia	United States	22310
94	Novartis Investigative Site	Charlottesville	Virginia	United States	22903
95	Novartis Investigative Site	Norfolk	Virginia	United States	23507
96	Novartis Investigative Site	Richmond	Virginia	United States	23226
97	Novartis Investigative Site	Roanoke	Virginia	United States	24018
98	Novartis Investigative Site	Issaquah	Washington	United States	98029
99	Novartis Investigative Site	Seattle	Washington	United States	98101
100	Novartis Investigative Site	Seattle	Washington	United States	98122-4379
101	Novartis Investigative Site	Milwaukee	Wisconsin	United States	53215
102	Novartis Investigative Site	Caba	Buenos Aires	Argentina	C1437JCP
103	Novartis Investigative Site	Buenos aires		Argentina	C1015ABR
104	Novartis Investigative Site	Belo Horizonte	Minas Gerais	Brazil	30150 221
105	Novartis Investigative Site	Porto Alegre	Rio Grande Do Sul	Brazil	90610-000
106	Novartis Investigative Site	Joinville	Santa Catarina	Brazil	89202-165
107	Novartis Investigative Site	São Paulo	SP	Brazil	08270-070
108	Novartis Investigative Site	Campina Grande do Sul		Brazil	83430 000
109	Novartis Investigative Site	Goiania		Brazil	74605 020
110	Novartis Investigative Site	Passo Fundo		Brazil	99010-080
111	Novartis Investigative Site	Rio de Janeiro		Brazil	22610-350
112	Novartis Investigative Site	Sao Paulo		Brazil	05651-901
113	Novartis Investigative Site	Edmonton	Alberta	Canada	T6R 2B7
114	Novartis Investigative Site	Burnaby	British Columbia	Canada	V5G 2X6
115	Novartis Investigative Site	Halifax	Nova Scotia	Canada	B3H 4K4
116	Novartis Investigative Site	Ottawa	Ontario	Canada	K1H 8L6
117	Novartis Investigative Site	Chicoutimi	Quebec	Canada	G7H 5H6
118	Novartis Investigative Site	Montreal	Quebec	Canada	H1T 2M4
119	Novartis Investigative Site	Montreal	Quebec	Canada	H3A 2B4
120	Novartis Investigative Site	Santiago		Chile	8380815
121	Novartis Investigative Site	Santiago		Chile	PISO 1
122	Novartis Investigative Site	Mexico	Distrito Federal	Mexico	03310
123	Novartis Investigative Site	Tlalnepantla	Edo De Mexico	Mexico	54055
124	Novartis Investigative Site	Monterrey	Nuevo León	Mexico	64000
125	Novartis Investigative Site	San Luis Potosi	San Luis Potosí	Mexico	78240
126	Novartis Investigative Site	Aguascalientes		Mexico	20127
127	Novartis Investigative Site	Chihuahua		Mexico	31000
128	Novartis Investigative Site	Chihuahua		Mexico	31203
129	Novartis Investigative Site	Monterrey		Mexico	64460
130	Novartis Investigative Site	Guaynabo		Puerto Rico	00968

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

• Study Protocol - Jul 20, 2015
• Statistical Analysis Plan - Nov 2, 2018

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01633112
• Other Study ID Numbers: CFTY720D2312
• First Posted: Jul 4, 2012
• Last Update Posted: May 28, 2019
• Last Verified: Apr 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Additional relevant MeSH terms: Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Sclerosis; Glatiramer Acetate; Fingolimod Hydrochloride; (T,G)-A-L

Study Results

Participant Flow

Pre-assignment Detail	A total of 1461 subjects were screened for participation in this study; of those, 1064 subjects were randomly assigned to study treatment

Arm/Group Title	FTY720 0.5 mg	FTY720 0.25 mg	GA 20 mg
Arm/Group Description	Fingolimod (FTY720) 0.5 mg orally once a day for up to 12 months	Fingolimod (FTY720) 0.25 mg orally once a day for up to 12 months	Glatiramer acetate (GA) 20 mg s.c. once a day for up to 12 months
Period Title: Overall Study
STARTED	352	370	342
COMPLETED	299	310	250
NOT COMPLETED	53	60	92

Baseline Characteristics

Arm/Group Title	FTY720 0.5 mg	FTY720 0.25 mg	GA 20 mg	Total
Arm/Group Description	Fingolimod (FTY720) 0.5 mg orally once a day for up to 12 months	Fingolimod (FTY720) 0.25 mg orally once a day for up to 12 months	Glatiramer acetate (GA) 20 mg s.c. once a day for up to 12 months	Total of all reporting groups
Overall Participants	352	370	342	1064
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	40.3 (11.12)	38.9 (11.01)	39.6 (10.80)	39.6 (10.98)
Sex: Female, Male (Count of Participants)
Female	264 75%	276 74.6%	252 73.7%	792 74.4%
Male	88 25%	94 25.4%	90 26.3%	272 25.6%
Race/Ethnicity, Customized (Count of Participants)
Caucasian	268 76.1%	279 75.4%	243 71.1%	790 74.2%
Black	34 9.7%	43 11.6%	41 12%	118 11.1%
Asian	0 0%	1 0.3%	0 0%	1 0.1%
Native American	8 2.3%	7 1.9%	9 2.6%	24 2.3%
Pacific Islander	0 0%	1 0.3%	0 0%	1 0.1%
Other	42 11.9%	39 10.5%	49 14.3%	130 12.2%

Outcome Measures

1. Primary Outcome

Title	Confirmed Annualized Relapse Rate
Description	Annualized relapse rate (ARR) was defined as the average number of confirmed relapses per year (i.e., the total number of confirmed relapses divided by the total days in the study multiplied by 365.25). The number of relapses included all the confirmed relapses experienced during the study from first dose to end of study.
Time Frame	up to 12 months

Outcome Measure Data

Analysis Population Description

Full-analysis set: All subjects who were randomly assigned and took at least 1 dose of study drug. Following the intent-to-treat principle, subjects were grouped according to the assigned treatment at randomization. Efficacy analyses were performed using the full analysis set unless otherwise notified.

Arm/Group Title	FTY720 0.5 mg	FTY720 0.25 mg	GA 20 mg
Arm/Group Description	Fingolimod (FTY720) 0.5 mg orally once a day for up to 12 months	Fingolimod (FTY720) 0.25 mg orally once a day for up to 12 months	Glatiramer acetate (GA) 20 mg s.c. once a day for up to 12 months
Measure Participants	345	366	324
Number (95% Confidence Interval) [relapses/year]	0.153	0.221	0.258

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	FTY720 0.5 mg, GA 20 mg
	Comments	H01: µ FTY 0.5 mg = µ GA versus HA1: µ FTY 0.5 mg ≠µ GA H02: µ FTY 0.25 mg = µ GA versus HA2: µ FTY 0.25 mg ≠µ GA
	Type of Statistical Test	Superiority
	Comments	For each of the 2 FTY720 doses, the null hypothesis was that there was no difference in the ARRs between subjects treated with FTY720 and those treated with GA versus the alternative hypothesis that there was a difference between the 2 treatment arms. In order to preserve the Type I experiment-wise error rate, the null hypothesis was rejected if the observed p-value for the between-treatment comparison was less than the significance level as specified in the multiplicity adjustment procedure.
Statistical Test of Hypothesis	p-Value	0.0138
	Comments
	Method	negative binomial regression model
	Comments	adjusted for treatment, geographical region, number of relapses in the previous year, baseline EDSS, and baseline Gd-enhancing T1 lesion count.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	FTY720 0.25 mg, GA 20 mg
	Comments	H01: µ FTY 0.5 mg = µ GA versus HA1: µ FTY 0.5 mg ≠µ GA H02: µ FTY 0.25 mg = µ GA versus HA2: µ FTY 0.25 mg ≠µ GA
	Type of Statistical Test	Superiority
	Comments	For each of the 2 FTY720 doses, the null hypothesis was that there was no difference in the ARRs between subjects treated with FTY720 and those treated with GA versus the alternative hypothesis that there was a difference between the 2 treatment arms. In order to preserve the Type I experiment-wise error rate, the null hypothesis was rejected if the observed p-value for the between-treatment comparison was less than the significance level as specified in the multiplicity adjustment procedure.
Statistical Test of Hypothesis	p-Value	0.4153
	Comments
	Method	negative binomial regression model
	Comments	adjusted for treatment, geographical region, number of relapses in the previous year, baseline EDSS, and baseline Gd-enhancing T1 lesion count.

2. Secondary Outcome

Title	New or Newly Enlarging T2 Lesions
Description	Inflammatory activity based on MRI measurement of new/newly enlarged T2 lesion count.
Time Frame	At 12 months/end of study

Outcome Measure Data

Analysis Population Description

Full-analysis set: All subjects who were randomly assigned and took at least 1 dose of study drug. Following the intent-to-treat principle, subjects were grouped according to the assigned treatment at randomization. Efficacy analyses were performed using the full analysis set unless otherwise notified.

Arm/Group Title	FTY720 0.5 mg	FTY720 0.25 mg	GA 20 mg
Arm/Group Description	Fingolimod (FTY720) 0.5 mg orally once a day for up to 12 months	Fingolimod (FTY720) 0.25 mg orally once a day for up to 12 months	Glatiramer acetate (GA) 20 mg s.c. once a day for up to 12 months
Measure Participants	345	366	324
Mean (Standard Deviation) [Lesions]	2.6 (5.42)	3.3 (6.94)	5.7 (10.71)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	FTY720 0.5 mg, GA 20 mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	negative binomial regression model
	Comments	Adjusted for treatment, geog. region, age, baseline T2 lesion count, baseline Gd-enhancing T1 lesion count, and the number of previous year relapses.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	FTY720 0.25 mg, GA 20 mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	negative binomial regression model
	Comments	Adjusted for treatment, geog. region, age, baseline T2 lesion count, baseline Gd-enhancing T1 lesion count, and the number of previous year relapses.

3. Secondary Outcome

Title	Number of Participants Free of New/Newly Enlarged T2 Lesions
Description	Inflammatory activity based on MRI measurement of new/newly enlarged T2 lesion count.
Time Frame	At 12 months/end of study

Outcome Measure Data

Analysis Population Description

Full-analysis set: All subjects who were randomly assigned and took at least 1 dose of study drug. Following the intent-to-treat principle, subjects were grouped according to the assigned treatment at randomization. Efficacy analyses were performed using the full analysis set unless otherwise notified.

Arm/Group Title	FTY720 0.5 mg	FTY720 0.25 mg	GA 20 mg
Arm/Group Description	Fingolimod (FTY720) 0.5 mg orally once a day for up to 12 months	Fingolimod (FTY720) 0.25 mg orally once a day for up to 12 months	Glatiramer acetate (GA) 20 mg s.c. once a day for up to 12 months
Measure Participants	345	366	324
Number [Participants]	156 44.3%	155 41.9%	96 28.1%

4. Secondary Outcome

Title	Change From Baseline in T2 Lesion Volume
Description	Inflammatory activity based on MRI measurement of new/newly enlarged T2 lesion volume
Time Frame	Baseline, 12 months/end of study

Outcome Measure Data

Analysis Population Description

Full-analysis set: All subjects who were randomly assigned and took at least 1 dose of study drug. Following the intent-to-treat principle, subjects were grouped according to the assigned treatment at randomization. Efficacy analyses were performed using the full analysis set unless otherwise notified.

Arm/Group Title	FTY720 0.5 mg	FTY720 0.25 mg	GA 20 mg
Arm/Group Description	Fingolimod (FTY720) 0.5 mg orally once a day for up to 12 months	Fingolimod (FTY720) 0.25 mg orally once a day for up to 12 months	Glatiramer acetate (GA) 20 mg s.c. once a day for up to 12 months
Measure Participants	345	366	324
Mean (Standard Deviation) [cubic centimeters (cc)]	-0.14 (1.583)	-0.05 (2.340)	0.42 (2.305)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	FTY720 0.5 mg, GA 20 mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	rank ANCOVA with covariates: adjusted for treatment, age, region, number of relapses experienced in the previous year, and baseline T2 lesion volume.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	FTY720 0.25 mg, GA 20 mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0060
	Comments
	Method	ANCOVA
	Comments	rank ANCOVA with covariates: adjusted for treatment, age, region, number of relapses experienced in the previous year, and baseline T2 lesion volume.

5. Secondary Outcome

Title	Gd Enhancing T1 Lesion Count
Description	Inflammatory activity based on MRI measurement of Gd enhancing T1 lesion count
Time Frame	At 12 months/end of study

Outcome Measure Data

Analysis Population Description

Full-analysis set: All subjects who were randomly assigned and took at least 1 dose of study drug. Following the intent-to-treat principle, subjects were grouped according to the assigned treatment at randomization. Efficacy analyses were performed using the full analysis set unless otherwise notified.

Arm/Group Title	FTY720 0.5 mg	FTY720 0.25 mg	GA 20 mg
Arm/Group Description	Fingolimod (FTY720) 0.5 mg orally once a day for up to 12 months	Fingolimod (FTY720) 0.25 mg orally once a day for up to 12 months	Glatiramer acetate (GA) 20 mg s.c. once a day for up to 12 months
Measure Participants	345	366	324
Mean (Standard Deviation) [lesions]	0.4 (1.57)	0.4 (1.56)	0.9 (3.67)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	FTY720 0.5 mg, GA 20 mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0167
	Comments
	Method	negative binomial regression model
	Comments	adjusted for treatment, age, geog. region, baseline T2 lesion count, baseline Gd-enhancing T1 lesion count, and the number of previous year relapses .

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	FTY720 0.25 mg, GA 20 mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0011
	Comments
	Method	negative binomial regression model
	Comments	adjusted for treatment, age, geog. region, baseline T2 lesion count, baseline Gd-enhancing T1 lesion count, and the number of previous year relapses.

6. Secondary Outcome

Title	Gd Enhancing T1 Lesion Volume
Description	Inflammatory activity based on MRI measurement of Gd enhancing T1 lesion count
Time Frame	Baseline, 12 months/end of study

Outcome Measure Data

Analysis Population Description

Full-analysis set: All subjects who were randomly assigned and took at least 1 dose of study drug. Following the intent-to-treat principle, subjects were grouped according to the assigned treatment at randomization. Efficacy analyses were performed using the full analysis set unless otherwise notified.

Arm/Group Title	FTY720 0.5 mg	FTY720 0.25 mg	GA 20 mg
Arm/Group Description	Fingolimod (FTY720) 0.5 mg orally once a day for up to 12 months	Fingolimod (FTY720) 0.25 mg orally once a day for up to 12 months	Glatiramer acetate (GA) 20 mg s.c. once a day for up to 12 months
Measure Participants	345	366	324
Baseline	0.31 (1.067)	0.32 (1.421)	0.22 (0.841)
Month 12/end of study	0.06 (0.215)	0.05 (0.181)	0.12 (0.450)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	FTY720 0.5 mg, GA 20 mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0052
	Comments
	Method	ANCOVA
	Comments	ranked ANCOVA with covariates: treatment, region, age, baseline Gd-enhancing T1 lesion volume, and number ofrelapses experienced in the previous year.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	FTY720 0.25 mg, GA 20 mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0636
	Comments
	Method	ANCOVA
	Comments	ranked ANCOVA with covariates: treatment, region, age, baseline Gd-enhancing T1 lesion volume, and number ofrelapses experienced in the previous year.

7. Secondary Outcome

Title	Percentage of Patients Free of New T1 Hypointense Lesions
Description	Based on MRI measures of new T1 hypointense lesions
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

Full-analysis set: All subjects who were randomly assigned and took at least 1 dose of study drug. Following the intent-to-treat principle, subjects were grouped according to the assigned treatment at randomization. Efficacy analyses were performed using the full analysis set unless otherwise notified.

Arm/Group Title	FTY720 0.5 mg	FTY720 0.25 mg	GA 20 mg
Arm/Group Description	Fingolimod (FTY720) 0.5 mg orally once a day for up to 12 months	Fingolimod (FTY720) 0.25 mg orally once a day for up to 12 months	Glatiramer acetate (GA) 20 mg s.c. once a day for up to 12 months
Measure Participants	345	366	324
Number [Percentage]	55.3	52.1	44.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	FTY720 0.5 mg, GA 20 mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0011
	Comments	adjusted for treatment, region, age, proper baseline T1 lesion variable, baseline Gd-enhancing T1 lesion count and number of previous year relapses.
	Method	Regression, Logistic
	Comments	pair-wise comparisons between treatment groups using a logistic regression model.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	FTY720 0.25 mg, GA 20 mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0146
	Comments	adjusted for treatment, region, age, proper baseline T1 lesion variable, baseline Gd-enhancing T1 lesion count and number of previous year relapses.
	Method	Regression, Logistic
	Comments	pair-wise comparisons between treatment groups using a logistic regression model.

8. Secondary Outcome

Title	Change From Baseline in TSQM Scales
Description	Treatment Satisfaction Questionnaire for Medication (TSQM) was developed and validated as a general measure for treatment satisfaction. Each scale score was calculated by summing individual items and then transformed to a 0-100 scale. Higher summary scores indicate better satisfaction with study drug.
Time Frame	6 months, 12 months/end of study

Outcome Measure Data

Analysis Population Description

Full-analysis set: All subjects who were randomly assigned and took at least 1 dose of study drug. Following the intent-to-treat principle, subjects were grouped according to the assigned treatment at randomization. Efficacy analyses were performed using the full analysis set unless otherwise notified.

Arm/Group Title	FTY720 0.5 mg	FTY720 0.25 mg	GA 20 mg
Arm/Group Description	Fingolimod (FTY720) 0.5 mg orally once a day for up to 12 months	Fingolimod (FTY720) 0.25 mg orally once a day for up to 12 months	Glatiramer acetate (GA) 20 mg s.c. once a day for up to 12 months
Measure Participants	345	366	324
Global Satisfaction (Month 6)	20.8 (28.15)	23.4 (27.04)	14.4 (25.42)
Global Satisfaction (Month 12)	19.2 (31.87)	20.5 (32.21)	9.4 (30.43)
Effectiveness (Month 6)	15.2 (25.96)	18.2 (25.05)	12.9 (23.43)
Effectiveness (Month 12)	16.8 (26.85)	17.9 (28.29)	8.0 (27.38)
Side Effects (Month 6)	16.9 (31.58)	18.8 (30.63)	9.3 (31.94)
Side Effects (Month 12)	16.2 (31.52)	17.2 (32.52)	7.6 (32.76)
Convenience (Month 6)	30.7 (25.76)	26.5 (25.93)	4.4 (20.73)
Convenience (Month 12)	29.5 (24.42)	26.5 (26.36)	0.8 (25.72)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	FTY720 0.5 mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Wilcoxon signed-rank test
	Comments	Global Satisfaction (Month 6): p-values for within treatment comparison from baseline

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	FTY720 0.25 mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Wilcoxon signed-rank test
	Comments	Global Satisfaction (Month 6): p-values for within treatment comparison from baseline

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	GA 20 mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Wilcoxon signed-rank test
	Comments	Global Satisfaction (Month 6): p-values for within treatment comparison from baseline

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	FTY720 0.5 mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Wilcoxon signed-rank test
	Comments	Global Satisfaction (Month 12): p-values for within treatment comparison from baseline

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	FTY720 0.25 mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Wilcoxon signed-rank test
	Comments	Global Satisfaction (Month 12): p-values for within treatment comparison from baseline

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	GA 20 mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Wilcoxon signed-rank test
	Comments	Global Satisfaction (Month 12): p-values for within treatment comparison from baseline

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	FTY720 0.5 mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Wilcoxon signed-rank test
	Comments	Effectiveness (Month 6): p-values for within treatment comparison from baseline

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	FTY720 0.25 mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Wilcoxon signed-rank test
	Comments	Effectiveness (Month 6): p-values for within treatment comparison from baseline

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	GA 20 mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Wilcoxon signed-rank test
	Comments	Effectiveness (Month 6): p-values for within treatment comparison from baseline

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	FTY720 0.5 mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Wilcoxon signed-rank test
	Comments	Effectiveness (Month 12): p-values for within treatment comparison from baseline

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	FTY720 0.25 mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Wilcoxon signed-rank test
	Comments	Effectiveness (Month 12): p-values for within treatment comparison from baseline

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	GA 20 mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Wilcoxon signed-rank test
	Comments	Effectiveness (Month 12): p-values for within treatment comparison from baseline

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	FTY720 0.5 mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Wilcoxon signed-rank test
	Comments	Side Effects (Month 6): p-values for within treatment comparison from baseline

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	FTY720 0.25 mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Wilcoxon signed-rank test
	Comments	Side Effects (Month 6): p-values for within treatment comparison from baseline

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	GA 20 mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0005
	Comments
	Method	Wilcoxon signed-rank test
	Comments	Side Effects (Month 6): p-values for within treatment comparison from baseline

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	FTY720 0.5 mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0051
	Comments
	Method	Wilcoxon signed-rank test
	Comments	Side Effects (Month 12): p-values for within treatment comparison from baseline

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	FTY720 0.25 mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Wilcoxon signed-rank test
	Comments	Side Effects (Month 12): p-values for within treatment comparison from baseline

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	GA 20 mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0051
	Comments
	Method	Wilcoxon signed-rank test
	Comments	Side Effects (Month 12): p-values for within treatment comparison from baseline

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	FTY720 0.5 mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Wilcoxon signed-rank test
	Comments	Convenience (Month 6): p-values for within treatment comparison from baseline

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	FTY720 0.25 mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Wilcoxon signed-rank test
	Comments	Convenience (Month 6): p-values for within treatment comparison from baseline

Statistical Analysis 21

Statistical Analysis Overview	Comparison Group Selection	GA 20 mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0068
	Comments
	Method	Wilcoxon signed-rank test
	Comments	Convenience (Month 6): p-values for within treatment comparison from baseline

Statistical Analysis 22

Statistical Analysis Overview	Comparison Group Selection	FTY720 0.5 mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Wilcoxon signed-rank test
	Comments	Convenience (Month 12): p-values for within treatment comparison from baseline

Statistical Analysis 23

Statistical Analysis Overview	Comparison Group Selection	FTY720 0.25 mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Wilcoxon signed-rank test
	Comments	Convenience (Month 12): p-values for within treatment comparison from baseline

Statistical Analysis 24

Statistical Analysis Overview	Comparison Group Selection	GA 20 mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4595
	Comments
	Method	Wilcoxon signed-rank test
	Comments	Convenience (Month 12): p-values for within treatment comparison from baseline

9. Secondary Outcome

Title	Percent Brain Volume Change From Baseline
Description	Using a Central MRI vendor to ensure calibrated MRI scanning equipment across all sites, MRI scans were performed on subjects following the established parameters and transferred to the central vendor for review of quality and assessment/evaluation.
Time Frame	Baseline, 12 months, end of study

Outcome Measure Data

Analysis Population Description

Full-analysis set: All subjects who were randomly assigned and took at least 1 dose of study drug. Following the intent-to-treat principle, subjects were grouped according to the assigned treatment at randomization. Efficacy analyses were performed using the full analysis set unless otherwise notified.

Arm/Group Title	FTY720 0.5 mg	FTY720 0.25 mg	GA 20 mg
Arm/Group Description	Fingolimod (FTY720) 0.5 mg orally once a day for up to 12 months	Fingolimod (FTY720) 0.25 mg orally once a day for up to 12 months	Glatiramer acetate (GA) 20 mg s.c. once a day for up to 12 months
Measure Participants	345	366	324
Mean (Standard Deviation) [Percentages of volume change]	-0.652 (0.7810)	-0.636 (0.8097)	-0.561 (0.7819)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	FTY720 0.5 mg, GA 20 mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1045
	Comments
	Method	ANCOVA
	Comments	rank ANCOVA model adjusted for treatment, region, age, the number of relapses experienced in the previous year, and baseline normalized brain volume

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	FTY720 0.25 mg, GA 20 mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1358
	Comments
	Method	ANCOVA
	Comments	rank ANCOVA model adjusted for treatment, region, age, the number of relapses experienced in the previous year, and baseline normalized brain volume

Adverse Events

Time Frame	Adverse Events (AEs) and Serious AEs (SAEs) were collected during treatment exposure and follow up where: AE summaries on the follow-up set were conducted for time periods defined by days relative to study drug discontinuation: days 1 - 45 after discontinuation, or day 46 or later after drug discontinuation. For SAEs (death and non-fatal ), all SAEs starting after the first dose date, including those starting > 45 days after study drug discontinuation, were included in the safety set summaries.
Arm/Group Title	Fingolimod 0.5 mg		FTY 0.25 mg		GA 20 mg		All@Patients
Arm/Group Description	Fingolimod (FTY720) 0.5 mg orally once a day for up to 12 months		Fingolimod (FTY720) 0.25 mg orally once a day for up to 12 months		Glatiramer acetate (GA) 20 mg s.c. once a day for up to 12 months		All patients in the trial
All Cause Mortality
	Fingolimod 0.5 mg		FTY 0.25 mg		GA 20 mg		All@Patients
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/345 (0%)		0/366 (0%)		0/324 (0%)		0/1035 (0%)
Serious Adverse Events
	Fingolimod 0.5 mg		FTY 0.25 mg		GA 20 mg		All@Patients
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	25/345 (7.2%)		32/366 (8.7%)		20/324 (6.2%)		77/1035 (7.4%)
Blood and lymphatic system disorders
Anaemia	1/345 (0.3%)		0/366 (0%)		0/324 (0%)		1/1035 (0.1%)
Leukocytosis	0/345 (0%)		2/366 (0.5%)		0/324 (0%)		2/1035 (0.2%)
Cardiac disorders
Acute myocardial infarction	0/345 (0%)		0/366 (0%)		1/324 (0.3%)		1/1035 (0.1%)
Angina pectoris	1/345 (0.3%)		1/366 (0.3%)		0/324 (0%)		2/1035 (0.2%)
Atrioventricular block second degree	1/345 (0.3%)		0/366 (0%)		0/324 (0%)		1/1035 (0.1%)
Bradycardia	0/345 (0%)		1/366 (0.3%)		0/324 (0%)		1/1035 (0.1%)
Cardiac arrest	0/345 (0%)		0/366 (0%)		1/324 (0.3%)		1/1035 (0.1%)
Coronary artery stenosis	0/345 (0%)		0/366 (0%)		1/324 (0.3%)		1/1035 (0.1%)
Palpitations	0/345 (0%)		0/366 (0%)		1/324 (0.3%)		1/1035 (0.1%)
Sinus bradycardia	1/345 (0.3%)		0/366 (0%)		0/324 (0%)		1/1035 (0.1%)
Tachycardia	0/345 (0%)		1/366 (0.3%)		0/324 (0%)		1/1035 (0.1%)
Ventricular fibrillation	0/345 (0%)		0/366 (0%)		1/324 (0.3%)		1/1035 (0.1%)
Ear and labyrinth disorders
Vertigo	0/345 (0%)		0/366 (0%)		1/324 (0.3%)		1/1035 (0.1%)
Endocrine disorders
Pituitary-dependent Cushing's syndrome	0/345 (0%)		1/366 (0.3%)		0/324 (0%)		1/1035 (0.1%)
Gastrointestinal disorders
Abdominal hernia	0/345 (0%)		1/366 (0.3%)		0/324 (0%)		1/1035 (0.1%)
Abdominal pain upper	1/345 (0.3%)		0/366 (0%)		0/324 (0%)		1/1035 (0.1%)
Hypoaesthesia oral	1/345 (0.3%)		0/366 (0%)		0/324 (0%)		1/1035 (0.1%)
Pancreatitis	1/345 (0.3%)		0/366 (0%)		1/324 (0.3%)		2/1035 (0.2%)
General disorders
Chest pain	1/345 (0.3%)		0/366 (0%)		0/324 (0%)		1/1035 (0.1%)
Feeling cold	1/345 (0.3%)		0/366 (0%)		0/324 (0%)		1/1035 (0.1%)
Gait disturbance	0/345 (0%)		2/366 (0.5%)		0/324 (0%)		2/1035 (0.2%)
Non-cardiac chest pain	1/345 (0.3%)		0/366 (0%)		0/324 (0%)		1/1035 (0.1%)
Pyrexia	1/345 (0.3%)		1/366 (0.3%)		0/324 (0%)		2/1035 (0.2%)
Hepatobiliary disorders
Cholecystitis	1/345 (0.3%)		1/366 (0.3%)		0/324 (0%)		2/1035 (0.2%)
Hepatic steatosis	1/345 (0.3%)		0/366 (0%)		0/324 (0%)		1/1035 (0.1%)
Infections and infestations
Appendicitis	0/345 (0%)		1/366 (0.3%)		0/324 (0%)		1/1035 (0.1%)
Arthritis bacterial	1/345 (0.3%)		0/366 (0%)		0/324 (0%)		1/1035 (0.1%)
Bronchitis	0/345 (0%)		1/366 (0.3%)		0/324 (0%)		1/1035 (0.1%)
Cellulitis	0/345 (0%)		1/366 (0.3%)		0/324 (0%)		1/1035 (0.1%)
Clostridium difficile colitis	1/345 (0.3%)		0/366 (0%)		0/324 (0%)		1/1035 (0.1%)
Device related sepsis	0/345 (0%)		0/366 (0%)		1/324 (0.3%)		1/1035 (0.1%)
Diverticulitis	0/345 (0%)		0/366 (0%)		1/324 (0.3%)		1/1035 (0.1%)
Extradural abscess	0/345 (0%)		1/366 (0.3%)		0/324 (0%)		1/1035 (0.1%)
Gastroenteritis	0/345 (0%)		1/366 (0.3%)		0/324 (0%)		1/1035 (0.1%)
Gastroenteritis viral	1/345 (0.3%)		0/366 (0%)		0/324 (0%)		1/1035 (0.1%)
Influenza	1/345 (0.3%)		0/366 (0%)		0/324 (0%)		1/1035 (0.1%)
Meningitis fungal	0/345 (0%)		1/366 (0.3%)		0/324 (0%)		1/1035 (0.1%)
Parainfluenzae virus infection	0/345 (0%)		1/366 (0.3%)		0/324 (0%)		1/1035 (0.1%)
Pneumonia	1/345 (0.3%)		0/366 (0%)		0/324 (0%)		1/1035 (0.1%)
Rhinovirus infection	1/345 (0.3%)		0/366 (0%)		0/324 (0%)		1/1035 (0.1%)
Sepsis	1/345 (0.3%)		0/366 (0%)		0/324 (0%)		1/1035 (0.1%)
Urinary tract infection	2/345 (0.6%)		1/366 (0.3%)		2/324 (0.6%)		5/1035 (0.5%)
Injury, poisoning and procedural complications
Craniocerebral injury	0/345 (0%)		1/366 (0.3%)		0/324 (0%)		1/1035 (0.1%)
Femoral neck fracture	0/345 (0%)		0/366 (0%)		1/324 (0.3%)		1/1035 (0.1%)
Femur fracture	0/345 (0%)		1/366 (0.3%)		0/324 (0%)		1/1035 (0.1%)
Foot fracture	0/345 (0%)		1/366 (0.3%)		0/324 (0%)		1/1035 (0.1%)
Metabolism and nutrition disorders
Dehydration	0/345 (0%)		0/366 (0%)		1/324 (0.3%)		1/1035 (0.1%)
Diabetic ketoacidosis	1/345 (0.3%)		0/366 (0%)		0/324 (0%)		1/1035 (0.1%)
Hypercalcaemia	0/345 (0%)		1/366 (0.3%)		0/324 (0%)		1/1035 (0.1%)
Hyperglycaemia	0/345 (0%)		1/366 (0.3%)		0/324 (0%)		1/1035 (0.1%)
Hypokalaemia	1/345 (0.3%)		0/366 (0%)		0/324 (0%)		1/1035 (0.1%)
Musculoskeletal and connective tissue disorders
Muscular weakness	0/345 (0%)		1/366 (0.3%)		0/324 (0%)		1/1035 (0.1%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acral lentiginous melanoma	0/345 (0%)		0/366 (0%)		1/324 (0.3%)		1/1035 (0.1%)
Basal cell carcinoma	3/345 (0.9%)		4/366 (1.1%)		0/324 (0%)		7/1035 (0.7%)
Biliary cancer metastatic	0/345 (0%)		1/366 (0.3%)		0/324 (0%)		1/1035 (0.1%)
Invasive ductal breast carcinoma	0/345 (0%)		0/366 (0%)		1/324 (0.3%)		1/1035 (0.1%)
Malignant melanoma	0/345 (0%)		0/366 (0%)		1/324 (0.3%)		1/1035 (0.1%)
Uterine leiomyoma	0/345 (0%)		1/366 (0.3%)		0/324 (0%)		1/1035 (0.1%)
Nervous system disorders
Cerebrovascular accident	1/345 (0.3%)		0/366 (0%)		0/324 (0%)		1/1035 (0.1%)
Cranial nerve paralysis	0/345 (0%)		0/366 (0%)		1/324 (0.3%)		1/1035 (0.1%)
Dysaesthesia	1/345 (0.3%)		0/366 (0%)		0/324 (0%)		1/1035 (0.1%)
Encephalopathy	1/345 (0.3%)		0/366 (0%)		0/324 (0%)		1/1035 (0.1%)
Headache	1/345 (0.3%)		3/366 (0.8%)		0/324 (0%)		4/1035 (0.4%)
Hemiparesis	1/345 (0.3%)		0/366 (0%)		0/324 (0%)		1/1035 (0.1%)
Monoparesis	1/345 (0.3%)		0/366 (0%)		0/324 (0%)		1/1035 (0.1%)
Multiple sclerosis relapse	4/345 (1.2%)		7/366 (1.9%)		7/324 (2.2%)		18/1035 (1.7%)
Paraparesis	1/345 (0.3%)		0/366 (0%)		0/324 (0%)		1/1035 (0.1%)
Seizure	1/345 (0.3%)		2/366 (0.5%)		0/324 (0%)		3/1035 (0.3%)
Syncope	0/345 (0%)		0/366 (0%)		2/324 (0.6%)		2/1035 (0.2%)
Psychiatric disorders
Depression suicidal	0/345 (0%)		1/366 (0.3%)		0/324 (0%)		1/1035 (0.1%)
Renal and urinary disorders
Acute kidney injury	1/345 (0.3%)		0/366 (0%)		1/324 (0.3%)		2/1035 (0.2%)
Urinary retention	1/345 (0.3%)		0/366 (0%)		0/324 (0%)		1/1035 (0.1%)
Reproductive system and breast disorders
Cervical dysplasia	0/345 (0%)		1/366 (0.3%)		0/324 (0%)		1/1035 (0.1%)
Dysmenorrhoea	1/345 (0.3%)		0/366 (0%)		0/324 (0%)		1/1035 (0.1%)
Menorrhagia	1/345 (0.3%)		0/366 (0%)		0/324 (0%)		1/1035 (0.1%)
Uterine enlargement	1/345 (0.3%)		0/366 (0%)		0/324 (0%)		1/1035 (0.1%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	2/345 (0.6%)		0/366 (0%)		0/324 (0%)		2/1035 (0.2%)
Hypoxia	1/345 (0.3%)		0/366 (0%)		0/324 (0%)		1/1035 (0.1%)
Pneumonia aspiration	1/345 (0.3%)		1/366 (0.3%)		0/324 (0%)		2/1035 (0.2%)
Pulmonary embolism	0/345 (0%)		1/366 (0.3%)		0/324 (0%)		1/1035 (0.1%)
Respiratory failure	1/345 (0.3%)		0/366 (0%)		0/324 (0%)		1/1035 (0.1%)
Vascular disorders
Hypertension	0/345 (0%)		1/366 (0.3%)		0/324 (0%)		1/1035 (0.1%)
Hypotension	0/345 (0%)		0/366 (0%)		1/324 (0.3%)		1/1035 (0.1%)
Other (Not Including Serious) Adverse Events
	Fingolimod 0.5 mg		FTY 0.25 mg		GA 20 mg		All@Patients
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	214/345 (62%)		245/366 (66.9%)		190/324 (58.6%)		649/1035 (62.7%)
Blood and lymphatic system disorders
Lymphopenia	23/345 (6.7%)		18/366 (4.9%)		1/324 (0.3%)		42/1035 (4.1%)
Gastrointestinal disorders
Diarrhoea	21/345 (6.1%)		23/366 (6.3%)		10/324 (3.1%)		54/1035 (5.2%)
Nausea	24/345 (7%)		30/366 (8.2%)		15/324 (4.6%)		69/1035 (6.7%)
General disorders
Fatigue	46/345 (13.3%)		46/366 (12.6%)		22/324 (6.8%)		114/1035 (11%)
Injection site erythema	0/345 (0%)		0/366 (0%)		34/324 (10.5%)		34/1035 (3.3%)
Injection site pain	0/345 (0%)		0/366 (0%)		36/324 (11.1%)		36/1035 (3.5%)
Injection site pruritus	0/345 (0%)		0/366 (0%)		26/324 (8%)		26/1035 (2.5%)
Injection site reaction	0/345 (0%)		0/366 (0%)		21/324 (6.5%)		21/1035 (2%)
Infections and infestations
Nasopharyngitis	23/345 (6.7%)		23/366 (6.3%)		14/324 (4.3%)		60/1035 (5.8%)
Upper respiratory tract infection	30/345 (8.7%)		35/366 (9.6%)		20/324 (6.2%)		85/1035 (8.2%)
Urinary tract infection	44/345 (12.8%)		43/366 (11.7%)		35/324 (10.8%)		122/1035 (11.8%)
Investigations
Alanine aminotransferase increased	20/345 (5.8%)		15/366 (4.1%)		4/324 (1.2%)		39/1035 (3.8%)
Musculoskeletal and connective tissue disorders
Arthralgia	15/345 (4.3%)		20/366 (5.5%)		13/324 (4%)		48/1035 (4.6%)
Back pain	17/345 (4.9%)		19/366 (5.2%)		18/324 (5.6%)		54/1035 (5.2%)
Pain in extremity	24/345 (7%)		24/366 (6.6%)		17/324 (5.2%)		65/1035 (6.3%)
Nervous system disorders
Dizziness	12/345 (3.5%)		27/366 (7.4%)		14/324 (4.3%)		53/1035 (5.1%)
Headache	51/345 (14.8%)		50/366 (13.7%)		27/324 (8.3%)		128/1035 (12.4%)
Psychiatric disorders
Anxiety	13/345 (3.8%)		21/366 (5.7%)		9/324 (2.8%)		43/1035 (4.2%)
Depression	23/345 (6.7%)		19/366 (5.2%)		18/324 (5.6%)		60/1035 (5.8%)
Insomnia	12/345 (3.5%)		27/366 (7.4%)		9/324 (2.8%)		48/1035 (4.6%)
Vascular disorders
Hypertension	26/345 (7.5%)		34/366 (9.3%)		12/324 (3.7%)		72/1035 (7%)

Limitations/Caveats

Terminated due to slow recruitment.

More Information

Certain Agreements

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.