EPOC: A 6-month, Randomized, Open-label, Patient OutComes, Safety and Tolerability Study of Fingolimod (FTY720) 0.5 mg/Day vs. Comparator in Patients With Relapsing Forms of Multiple Sclerosis

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01216072
• Collaborator: (none)
• Enrollment: 1,053
• Locations: 149
• Arms: 2
• Duration (Months): 24
• Patients Per Site: 7.1
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the change in patient-reported outcomes, physician assessment of a change as well as safety and tolerability in patients with Relapsing Forms of Multiple Sclerosis on previous Disease Modifying Therapy (DMT) who are randomized to one of two treatment arms: fingolimod vs. standard of care DMT.

Condition or Disease	Intervention/Treatment	Phase
Relapsing Forms of Multiple Sclerosis	Drug: Fingolimod; Drug: Standard MS DMTs	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 1053 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A 6-month, Randomized, Active Comparator, Open-label, Multi-Center Study to Evaluate Patient OutComes, Safety and Tolerability of Fingolimod (FTY720) 0.5 mg/Day in Patients With Relapsing Forms of Multiple Sclerosis Who Are Candidates for MS Therapy Change From Previous Disease Modifying Therapy (EPOC)
• Study Start Date: Aug 1, 2010
• Actual Primary Completion Date: Aug 1, 2012
• Actual Study Completion Date: Aug 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Fingolimod Patients randomized in this arm received Fingolimod 0.5 mg/day oral capsule for 6 months core period .	Drug: Fingolimod; 0.5 mg/day oral capsule; Other Names: GILENYA™
Active Comparator: Multiple Sclerosis Disease Modifying Treatments (MS DMTs) Patients randomized in this arm received selected Standard MS DMT such as Interferon beta-1b or Interferon beta-1a or Glatiramer acetate for 6 months. An open-label extension of up to 3 months of treatment with fingolimod was to be available for patients in the DMT arm who successfully completed all study visits.	Drug: Standard MS DMTs; Other Names: Avonex®, Copaxone®, Rebif®, Betaseron®, Extavia®

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in the Global Satisfaction Subscale of the Treatment Satisfaction Questionnaire for Medication (TSQM) at Month 6 [Baseline, Month 6]

   The TSQM was developed and validated as a general measure for treatment satisfaction. It contains 14 items assessing the following 4 domains: effectiveness (sum of scores for questions 1 - 3), side effects (sum of scores for questions 4 - 8), convenience (sum of scores for questions 9 - 11) and Global Satisfaction (sum of scores for questions 12 - 14). The primary analysis was on Global Satisfaction. Question 12 scored as 1(not at all confident) to 5 (extremely confident); question 13 scored as 1(not at all certain) to 5(extremely certain); and question 14 scored as 1(extremely dissatisfied) to 7(extremely satisfied). The scores of the domain were added together and an algorithm was used to create a score of 0 to 100. Higher scores indicated greater satisfaction. A positive change from baseline indicates improvement.

Secondary Outcome Measures

1. Number of Patients Who Experienced Adverse Events, Serious Adverse Events and Death [9 months (6 month core + 3 month Extension)]

   In this analysis, patients with all (serious and non-serious) adverse events, serious adverse events and death were reported.

2. Change From Baseline in Patient-reported Activities of Daily Living (ADL) Using the Multiple Sclerosis Activities Scale (PRIMUS-Activities) at Month 6 [Baseline, Month 6]

   The PRIMUS activity measure is a 15-item assessment of patient-reported ADL. The PRIMUS-Activities total score was calculated by summing the 15 item scores after recoding the responses from 1 - 3 to 0 - 2. Totals scores range from 0 to 30 with higher scores indicating greater activity limitation. If no more than 20% of the items were missing, the total score was the product of the mean response of the non-missing items and the total number of items. If more than 20% of all items were missing, the total score was set to missing. A negative change from baseline indicates improvement.

3. Change From Baseline in Patient-reported Fatigue Using the Fatigue Severity Scale (FSS) [Baseline, Month 3, Month 6]

   The Fatigue Severity Scale (FSS) is a 9-item assessment scale measuring fatigue and its effects, using a scale from 1 to 7, with higher scores indicating greater fatigue, or greater negative effects of fatigue on daily living. The FSS 9 item total score was calculated by summing the first 9 item scores and dividing by the number of non-missing items. If no more than 20% of the items were missing, the total score was the product of the mean response of the non missing items and the total number of items. If more than 20% of all items were missing, the total score was set to missing. A negative change from baseline indicates improvement.

4. Change From Baseline in the Patient-reported Effectiveness Subscale Using the TSQM v1.4 [Baseline, Month 6]

   The effectiveness scale was scored as follows: 1(extremely dissatisfied) to 7(extremely satisfied). The scores of the domain were added together and an algorithm was used to create a score of 0 to 100. Higher scores indicated greater satisfaction. A positive change from baseline indicates improvement.

5. Change From Baseline in the Patient-reported Side Effects Subscale Using the TSQM v1.4 [Baseline, Month 6]

   The Side Effects subscale was scored as follows: question 4 scored as 0(no) or 1(yes); question 5 scored as 1(extremely bothersome) to 5(not at all bothersome); and questions 6 - 8 scored as 1(a great deal) to 5(not at all). The scores of the domain were added together and an algorithm was used to create a score of 0 to 100. Higher scores indicated greater satisfaction. A positive change from baseline indicates improvement.

6. Change From Baseline in the Patient-reported Convenience Subscale Using the TSQM v1.4 [Baseline, Month 6]

   The convenience subscale was scored as follows: questions 9 and 10 scored as 1(extremely difficult) to 7 (extremely easy), and question 11 scored as 1(extremely inconvenient) to 7 (extremely convenient). The scores of the domain were added together and an algorithm was used to create a score of 0 to 100. Higher scores indicated greater satisfaction. A positive change from baseline indicates improvement.

7. Change From Baseline in Patient-reported Health-related Quality-of-life Using the Short Form Health Survey v2 Standard (SF-36 v2) [Baseline, Month 6]

   The SF-36v2 is a validated health-related quality of life instrument used in numerous disease states, including MS. It is a self-administered survey that measures 8 domains of health including: physical functioning, role limitations due to physical health, bodily pain, general health perceptions, vitality, social functioning, role limitations due to emotional problems and general mental health. Additionally, two summary scale scores can be calculated: the Physical Component Summary (PCS) and the Mental Component Summary (MCS). If half or more questions within a domain were answered, then a score was calculated for that domain. Otherwise, the patient score for that domain was set to missing. If the patient was missing any 1 of the 8 scale scores, then the physical and mental component scores were set to missing. An algorithm was used to create a score from 0 to 100 for each domain score and component score. A positive change from baseline indicates improvement.

8. Change From Baseline in Patient-reported Depression Using the Beck Depression Inventory (BDI-II) [Baseline, Month 3, Month 6]

   The Beck Depression Inventory (BDI-II) is a 21-question multiple-choice self-report inventory. Each item is scored from 0 to 3. The questions in the BDI-II refer to how the patient has been feeling over the past two weeks specifically. The BDI-II total score was calculated by summing the 21 item scores. Final scores ranged from 0 to 63 where higher scores indicated more severe depression. If no more than 20% of the items were missing, the total score was the product of the mean response of the non-missing items and the total number of items. If more than 20% of all items were missing, the total score was set to missing. A negative change indicates improvement.

9. Physician-reported Clinical Global Impression of Improvement (CGI-I) [Month 3, Month 6]

   The CGI-I is a rating scale allowing a physician-reported global evaluation of the subject's improvement over time. The Investigator assessed the subject's clinical change relative to the symptoms at baseline on the CGI-I, a seven-point scale, with rating as follows: 1=Very much improved, 2=Much improved, 3=Minimally improved, 4=No change, 5=Minimally worse, 6=Much worse, 7=Very much worse. The assessments were completed at Month 3 and Month 6. A lower score indicates improvement.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Relapsing forms of MS

• Expanded Disability Status Scale (EDSS) 0-5.5

• Continuous treatment with MS DMT for a minimum of 6 months

• Fingolimod naive

Exclusion Criteria:

• Immune system diseases other than MS

• Active macular edema

• History of selected prior infections and criteria for immunizations

• History of selected immune system treatments and/or medications

• Selected cardiovascular, pulmonary, or hepatic conditions

• Selected abnormal laboratory values

• Pregnant or nursing women

Other protocol-defined inclusion/exclusion criteria applied

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Birmingham	Alabama	United States	35209
2	Novartis Investigative Site	Cullman	Alabama	United States	35058
3	Novartis Investigative Site	Phoenix	Arizona	United States	85004
4	Novartis Investigative Site	Phoenix	Arizona	United States	85006
5	Novartis Investigative Site	Phoenix	Arizona	United States	85013
6	Novartis Investigative Site	Phoenix	Arizona	United States	85032
7	Novartis Investigative Site	Tucson	Arizona	United States	85741
8	Novartis Investigative Site	Anaheim	California	United States	92801
9	Novartis Investigative Site	Berkeley	California	United States	94705
10	Novartis Investigative Site	Fresno	California	United States	93710
11	Novartis Investigative Site	Fullerton	California	United States	92835
12	Novartis Investigative Site	La Habra	California	United States	90631
13	Novartis Investigative Site	Loma Linda	California	United States	92354
14	Novartis Investigative Site	Newport Beach	California	United States	92660
15	Novartis Investigative Site	Oceanside	California	United States	92056
16	Novartis Investigative Site	Sacramento	California	United States	95817
17	Novartis Investigative Site	Walnut Creek	California	United States	94598
18	Novartis Investigative Site	Boulder	Colorado	United States	80304
19	Novartis Investigative Site	Colorado Springs	Colorado	United States	80920
20	Novartis Investigative Site	Fort Collins	Colorado	United States	80528
21	Novartis Investigative Site	Fairfield	Connecticut	United States	06824
22	Novartis Investigative Site	New London	Connecticut	United States	06320
23	Novartis Investigative Site	Stratford	Connecticut	United States	06615
24	Novartis Investigative Site	Dover	Delaware	United States	19901
25	Novartis Investigative Site	Newark	Delaware	United States	19713
26	Novartis Investigative Site	Atlantis	Florida	United States	33462-6608
27	Novartis Investigative Site	Bradenton	Florida	United States	32405
28	Novartis Investigative Site	Doral	Florida	United States	33166
29	Novartis Investigative Site	Fort Lauderdale	Florida	United States	33308
30	Novartis Investigative Site	Hollywood	Florida	United States	33021
31	Novartis Investigative Site	Jacksonville	Florida	United States	32209
32	Novartis Investigative Site	Jacksonville	Florida	United States	32216
33	Novartis Investigative Site	Lighthouse Point	Florida	United States	33064
34	Novartis Investigative Site	Maitland	Florida	United States	32751
35	Novartis Investigative Site	Miami	Florida	United States	33015
36	Novartis Investigative Site	Miami	Florida	United States	33133
37	Novartis Investigative Site	Pompano Beach	Florida	United States	33060
38	Novartis Investigative Site	Ponte Vedra Beach	Florida	United States	32082-4627
39	Novartis Investigative Site	Port Orange	Florida	United States	32127
40	Novartis Investigative Site	Sarasota	Florida	United States	34243
41	Novartis Investigative Site	St. Petersburg	Florida	United States	33713
42	Novartis Investigative Site	Sunrise	Florida	United States	33351
43	Novartis Investigative Site	Tallahassee	Florida	United States	32308
44	Novartis Investigative Site	Tampa	Florida	United States	33609
45	Novartis Investigative Site	Tampa	Florida	United States	33612
46	Novartis Investigative Site	Vero Beach	Florida	United States	32960
47	Novartis Investigative Site	West Palm Beach	Florida	United States	33407
48	Novartis Investigative Site	Atlanta	Georgia	United States	30302
49	Novartis Investigative Site	Atlanta	Georgia	United States	30309
50	Novartis Investigative Site	Columbus	Georgia	United States	31901
51	Novartis Investigative Site	Decatur	Georgia	United States	30083
52	Novartis Investigative Site	Idaho Falls	Idaho	United States	83402
53	Novartis Investigative Site	Elk Grove Village	Illinois	United States	60007
54	Novartis Investigative Site	Evanston	Illinois	United States	60201
55	Novartis Investigative Site	Flossmoor	Illinois	United States	60422
56	Novartis Investigative Site	Northbrook	Illinois	United States	60062
57	Novartis Investigative Site	Anderson	Indiana	United States	46011
58	Novartis Investigative Site	Indianapolis	Indiana	United States	46202-5111
59	Novartis Investigative Site	Indianapolis	Indiana	United States	46256
60	Novartis Investigative Site	Merrillville	Indiana	United States	46410
61	Novartis Investigative Site	Valparaiso	Indiana	United States	46383
62	Novartis Investigative Site	Des Moines	Iowa	United States	50314-2611
63	Novartis Investigative Site	Lenexa	Kansas	United States	66214
64	Novartis Investigative Site	Baton Rouge	Louisiana	United States	70809
65	Novartis Investigative Site	Destrehan	Louisiana	United States	70047
66	Novartis Investigative Site	Hammond	Louisiana	United States	70403
67	Novartis Investigative Site	Metairie	Louisiana	United States	70001
68	Novartis Investigative Site	Shreveport	Louisiana	United States	71101
69	Novartis Investigative Site	Shreveport	Louisiana	United States	71130
70	Novartis Investigative Site	Baltimore	Maryland	United States	21201
71	Novartis Investigative Site	Bethesda	Maryland	United States	20814
72	Novartis Investigative Site	Boston	Massachusetts	United States	02135
73	Novartis Investigative Site	Springfield	Massachusetts	United States	01104
74	Novartis Investigative Site	Worcester	Massachusetts	United States	01608
75	Novartis Investigative Site	Worcester	Massachusetts	United States	01665
76	Novartis Investigative Site	Detroit	Michigan	United States	48201
77	Novartis Investigative Site	Grand Rapids	Michigan	United States	49503
78	Novartis Investigative Site	Kalamazoo	Michigan	United States	49007
79	Novartis Investigative Site	Southfield	Michigan	United States	48034
80	Novartis Investigative Site	Bolivar	Missouri	United States	65613
81	Novartis Investigative Site	Kansas City	Missouri	United States	64111
82	Novartis Investigative Site	Kansas City	Missouri	United States	64132
83	Novartis Investigative Site	Nixa	Missouri	United States	65714-7807
84	Novartis Investigative Site	North Kansas City	Missouri	United States	64116
85	Novartis Investigative Site	St. Louis	Missouri	United States	63104
86	Novartis Investigative Site	Billings	Montana	United States	59102
87	Novartis Investigative Site	Freehold	New Jersey	United States	07728
88	Novartis Investigative Site	Somerset	New Jersey	United States	08873
89	Novartis Investigative Site	Teaneck	New Jersey	United States	07666
90	Novartis Investigative Site	Toms River	New Jersey	United States	08755
91	Novartis Investigative Site	Amherst	New York	United States	14226
92	Novartis Investigative Site	Latham	New York	United States	12110
93	Novartis Investigative Site	New York	New York	United States	10023
94	Novartis Investigative Site	Patchogue	New York	United States	11772
95	Novartis Investigative Site	Plainview	New York	United States	11803
96	Novartis Investigative Site	Asheville	North Carolina	United States	28806
97	Novartis Investigative Site	Burlington	North Carolina	United States	27215
98	Novartis Investigative Site	Charlotte	North Carolina	United States	28204
99	Novartis Investigative Site	Charlotte	North Carolina	United States	28207
100	Novartis Investigative Site	Greensboro	North Carolina	United States	27401
101	Novartis Investigative Site	Greenville	North Carolina	United States	27834
102	Novartis Investigative Site	Raleigh	North Carolina	United States	27607
103	Novartis Investigative Site	Salisbury	North Carolina	United States	28144
104	Novartis Investigative Site	Wilmington	North Carolina	United States	28401
105	Novartis Investigative Site	Winston-Salem	North Carolina	United States	27103
106	Novartis Investigative Site	Akron	Ohio	United States	44320
107	Novartis Investigative Site	Bellevue	Ohio	United States	44811
108	Novartis Investigative Site	Canton	Ohio	United States	44718
109	Novartis Investigative Site	Cincinnati	Ohio	United States	45219
110	Novartis Investigative Site	Columbus	Ohio	United States	43221
111	Novartis Investigative Site	Uniontown	Ohio	United States	44685
112	Novartis Investigative Site	Oklahoma City	Oklahoma	United States	73112
113	Novartis Investigative Site	Corvallis	Oregon	United States	97330
114	Novartis Investigative Site	Eugene	Oregon	United States	97401
115	Novartis Investigative Site	Medford	Oregon	United States	97504
116	Novartis Investigative Site	Portland	Oregon	United States	97223
117	Novartis Investigative Site	Monroeville	Pennsylvania	United States	15146
118	Novartis Investigative Site	Rumford	Rhode Island	United States	02916
119	Novartis Investigative Site	Beufort	South Carolina	United States	29902
120	Novartis Investigative Site	Columbia	Tennessee	United States	38401
121	Novartis Investigative Site	Cordova	Tennessee	United States	38018
122	Novartis Investigative Site	Knoxville	Tennessee	United States	37934
123	Novartis Investigative Site	Nashville	Tennessee	United States	37205
124	Novartis Investigative Site	Austin	Texas	United States	78756
125	Novartis Investigative Site	Colleyville	Texas	United States	76034
126	Novartis Investigative Site	Dallas	Texas	United States	75204
127	Novartis Investigative Site	Houston	Texas	United States	77025
128	Novartis Investigative Site	Lubbock	Texas	United States	79410
129	Novartis Investigative Site	Plano	Texas	United States	75075
130	Novartis Investigative Site	Round Rock	Texas	United States	78681
131	Novartis Investigative Site	San Antonio	Texas	United States	78229
132	Novartis Investigative Site	San Antonio	Texas	United States	78258
133	Novartis Investigative Site	Sherman	Texas	United States	75092
134	Novartis Investigative Site	Salt Lake City	Utah	United States	84103
135	Novartis Investigative Site	Newport News	Virginia	United States	23606
136	Novartis Investigative Site	Richmond	Virginia	United States	23226
137	Novartis Investigative Site	Roanoke	Virginia	United States	24014
138	Novartis Investigative Site	Vienna	Virginia	United States	22182
139	Novartis Investigative Site	Kirkland	Washington	United States	98034
140	Novartis Investigative Site	Seattle	Washington	United States	98122
141	Novartis Investigative Site	Seattle	Washington	United States	98144
142	Novartis Investigative Site	Morgantown	West Virginia	United States	26506-9260
143	Novartis Investigative Site	Calgary	Alberta	Canada	T2N 2T9
144	Novartis Investigative Site	Nepean	Ontario	Canada	K2G 6E2
145	Novartis Investigative Site	Ottawa	Ontario	Canada	K1H 8L6
146	Novartis Investigative Site	Greenfield Park	Quebec	Canada	J4V 2J2
147	Novartis Investigative Site	Montreal	Quebec	Canada	H1T 2M4
148	Novartis Investigative Site	Montreal	Quebec	Canada	H3A 2B4
149	Novartis Investigative Site	Guaynabo		Puerto Rico	00969

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Click here for more information about this study:

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01216072
• Other Study ID Numbers: CFTY720DUS01
• First Posted: Oct 7, 2010
• Last Update Posted: Feb 10, 2014
• Last Verified: Jan 1, 2014

• Keywords provided by Novartis Pharmaceuticals: Relapsing Forms of Multiple Sclerosis; Disease Modifying Therapy; fingolimod; Patient Reported Outcomes
• Additional relevant MeSH terms: Multiple Sclerosis; Sclerosis; Fingolimod Hydrochloride; Interferon beta-1b

Study Results

Participant Flow

Pre-assignment Detail	Patients randomized in a 3:1 ratio to either fingolimod (0.5 mg/day) or MS DMT.

Arm/Group Title	Fingolimod	Multiple Sclerosis Disease Modifying Treatments (MS DMTs)
Arm/Group Description	Patients randomized in this arm received Fingolimod 0.5 mg/day oral capsule for 6 months core period.	Patients randomized in this arm received selected Standard MS DMT such as Interferon beta-1b or Interferon beta-1a or Glatiramer acetate for 6 months. An open-label extension of up to 3 months of treatment with fingolimod was to be available for patients in the DMT arm who successfully completed all study visits.
Period Title: Open-Label Core Period ( 6 Months)
STARTED	790	263
Full Analysis Set	789	263
Safety Set	783	245
COMPLETED	714	229
NOT COMPLETED	76	34
Period Title: Open-Label Core Period ( 6 Months)
STARTED	0	195
Safety Set	0	193
COMPLETED	0	181
NOT COMPLETED	0	14

Baseline Characteristics

Arm/Group Title	Fingolimod	Multiple Sclerosis Disease Modifying Treatments (MS DMTs)	Total
Arm/Group Description	Patients randomized in this arm received Fingolimod 0.5 mg/day oral capsule for 6 months core period.	Patients randomized in this arm received selected Standard MS DMT such as Interferon beta-1b or Interferon beta-1a or Glatiramer acetate for 6 months. An open-label extension of up to 3 months of treatment with fingolimod was to be available for patients in the DMT arm who successfully completed all study visits.	Total of all reporting groups
Overall Participants	790	263	1053
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	46 (9.82)	45.1 (9.82)	45.8 (9.82)
Sex: Female, Male (Count of Participants)
Female	601 76.1%	208 79.1%	809 76.8%
Male	189 23.9%	55 20.9%	244 23.2%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in the Global Satisfaction Subscale of the Treatment Satisfaction Questionnaire for Medication (TSQM) at Month 6
Description	The TSQM was developed and validated as a general measure for treatment satisfaction. It contains 14 items assessing the following 4 domains: effectiveness (sum of scores for questions 1 - 3), side effects (sum of scores for questions 4 - 8), convenience (sum of scores for questions 9 - 11) and Global Satisfaction (sum of scores for questions 12 - 14). The primary analysis was on Global Satisfaction. Question 12 scored as 1(not at all confident) to 5 (extremely confident); question 13 scored as 1(not at all certain) to 5(extremely certain); and question 14 scored as 1(extremely dissatisfied) to 7(extremely satisfied). The scores of the domain were added together and an algorithm was used to create a score of 0 to 100. Higher scores indicated greater satisfaction. A positive change from baseline indicates improvement.
Time Frame	Baseline, Month 6

Outcome Measure Data

Analysis Population Description

This analysis was conducted using the Full Analysis Set. The Full Analysis Set comprised all randomized patients to whom study medication was assigned. Patients with both baseline and 6 month assessments were included in this analysis.

Arm/Group Title	Fingolimod	Multiple Sclerosis Disease Modifying Treatments (MS DMTs)
Arm/Group Description	Patients randomized in this arm received Fingolimod 0.5 mg/day oral capsule for 6 months core period.	Patients randomized in this arm received selected Standard MS DMT such as Interferon beta-1b or Interferon beta-1a or Glatiramer acetate for 6 months. An open-label extension of up to 3 months of treatment with fingolimod was to be available for patients in the DMT arm who successfully completed all study visits.
Measure Participants	714	221
Mean (Standard Deviation) [units on a scale]	22.5 (27.1)	3.5 (20.57)

2. Secondary Outcome

Title	Number of Patients Who Experienced Adverse Events, Serious Adverse Events and Death
Description	In this analysis, patients with all (serious and non-serious) adverse events, serious adverse events and death were reported.
Time Frame	9 months (6 month core + 3 month Extension)

Outcome Measure Data

Analysis Population Description

Safety Set included all patients who received at least one dose of study drug.

Arm/Group Title	Fingolimod	Multiple Sclerosis Disease Modifying Treatments (MS DMTs)	Extension Fingolimod Period
Arm/Group Description	Patients randomized in this arm received Fingolimod 0.5 mg/day oral capsule for 6 months core period.	Patients randomized in this arm received selected Standard MS DMT such as Interferon beta-1b or Interferon beta-1a or Glatiramer acetate for 6 months.	An open-label extension of up to 3 months of treatment with fingolimod was to be available for patients in the DMT arm who successfully completed all study visits.
Measure Participants	783	245	193
Adverse Events (serious and non-serious)	617 78.1%	152 57.8%	123 11.7%
Serious Adverse Events	31 3.9%	5 1.9%	7 0.7%
Death	0 0%	0 0%	0 0%

3. Secondary Outcome

Title	Change From Baseline in Patient-reported Activities of Daily Living (ADL) Using the Multiple Sclerosis Activities Scale (PRIMUS-Activities) at Month 6
Description	The PRIMUS activity measure is a 15-item assessment of patient-reported ADL. The PRIMUS-Activities total score was calculated by summing the 15 item scores after recoding the responses from 1 - 3 to 0 - 2. Totals scores range from 0 to 30 with higher scores indicating greater activity limitation. If no more than 20% of the items were missing, the total score was the product of the mean response of the non-missing items and the total number of items. If more than 20% of all items were missing, the total score was set to missing. A negative change from baseline indicates improvement.
Time Frame	Baseline, Month 6

Outcome Measure Data

Analysis Population Description

This analysis was conducted using the Full Analysis Set. The Full Analysis Set comprised all randomized patients to whom study medication was assigned. Patients with both baseline and 6 month assessments were included in this analysis. Missing values were imputed using the Last Observation Carried Forward (LOCF) method.

Arm/Group Title	Fingolimod	Multiple Sclerosis Disease Modifying Treatments (MS DMTs)
Arm/Group Description	Patients randomized in this arm received Fingolimod 0.5 mg/day oral capsule for 6 months core period.	Patients randomized in this arm received selected Standard MS DMT such as Interferon beta-1b or Interferon beta-1a or Glatiramer acetate for 6 months. An open-label extension of up to 3 months of treatment with fingolimod was to be available for patients in the DMT arm who successfully completed all study visits.
Measure Participants	734	234
Mean (Standard Deviation) [units on a scale]	-0.6 (4.51)	-0.2 (4.97)

4. Secondary Outcome

Title	Change From Baseline in Patient-reported Fatigue Using the Fatigue Severity Scale (FSS)
Description	The Fatigue Severity Scale (FSS) is a 9-item assessment scale measuring fatigue and its effects, using a scale from 1 to 7, with higher scores indicating greater fatigue, or greater negative effects of fatigue on daily living. The FSS 9 item total score was calculated by summing the first 9 item scores and dividing by the number of non-missing items. If no more than 20% of the items were missing, the total score was the product of the mean response of the non missing items and the total number of items. If more than 20% of all items were missing, the total score was set to missing. A negative change from baseline indicates improvement.
Time Frame	Baseline, Month 3, Month 6

Outcome Measure Data

Analysis Population Description

This analysis was conducted using the Full Analysis Set. The Full Analysis Set comprised all randomized patients to whom study medication was assigned. Patients with baseline to 3 month assessments and/or baseline to 6 month assessments were included in this analysis.

Arm/Group Title	Fingolimod	Multiple Sclerosis Disease Modifying Treatments (MS DMTs)
Arm/Group Description	Patients randomized in this arm received Fingolimod 0.5 mg/day oral capsule for 6 months core period.	Patients randomized in this arm received selected Standard MS DMT such as Interferon beta-1b or Interferon beta-1a or Glatiramer acetate for 6 months. An open-label extension of up to 3 months of treatment with fingolimod was to be available for patients in the DMT arm who successfully completed all study visits.
Measure Participants	789	263
Change from Baseline to Month 3 (n=710,232)	-0.3 (1.24)	0.0 (1.14)
Change from Baseline to Month 6 (n=687,218)	-0.4 (1.24)	0.0 (1.13)

5. Secondary Outcome

Title	Change From Baseline in the Patient-reported Effectiveness Subscale Using the TSQM v1.4
Description	The effectiveness scale was scored as follows: 1(extremely dissatisfied) to 7(extremely satisfied). The scores of the domain were added together and an algorithm was used to create a score of 0 to 100. Higher scores indicated greater satisfaction. A positive change from baseline indicates improvement.
Time Frame	Baseline, Month 6

Outcome Measure Data

Analysis Population Description

This analysis was conducted using the Full Analysis Set. The Full Analysis Set comprised all randomized patients to whom study medication was assigned. Patients with both baseline and 6 month assessments were included in this analysis.

Arm/Group Title	Fingolimod	Multiple Sclerosis Disease Modifying Treatments (MS DMTs)
Arm/Group Description	Patients randomized in this arm received Fingolimod 0.5 mg/day oral capsule for 6 months core period.	Patients randomized in this arm received selected Standard MS DMT such as Interferon beta-1b or Interferon beta-1a or Glatiramer acetate for 6 months. An open-label extension of up to 3 months of treatment with fingolimod was to be available for patients in the DMT arm who successfully completed all study visits.
Measure Participants	723	225
Mean (Standard Deviation) [units on a scale]	15.5 (27.53)	2.8 (19.05)

6. Secondary Outcome

Title	Change From Baseline in the Patient-reported Side Effects Subscale Using the TSQM v1.4
Description	The Side Effects subscale was scored as follows: question 4 scored as 0(no) or 1(yes); question 5 scored as 1(extremely bothersome) to 5(not at all bothersome); and questions 6 - 8 scored as 1(a great deal) to 5(not at all). The scores of the domain were added together and an algorithm was used to create a score of 0 to 100. Higher scores indicated greater satisfaction. A positive change from baseline indicates improvement.
Time Frame	Baseline, Month 6

Outcome Measure Data

Analysis Population Description

This analysis was conducted using the Full Analysis Set. The Full Analysis Set comprised all randomized patients to whom study medication was assigned. Patients with both baseline and 6 month assessments were included in this analysis.

Arm/Group Title	Fingolimod	Multiple Sclerosis Disease Modifying Treatments (MS DMTs)
Arm/Group Description	Patients randomized in this arm received Fingolimod 0.5 mg/day oral capsule for 6 months core period.	Patients randomized in this arm received selected Standard MS DMT such as Interferon beta-1b or Interferon beta-1a or Glatiramer acetate for 6 months. An open-label extension of up to 3 months of treatment with fingolimod was to be available for patients in the DMT arm who successfully completed all study visits.
Measure Participants	708	219
Mean (Standard Deviation) [units on a scale]	22.9 (29.89)	3.5 (23.18)

7. Secondary Outcome

Title	Change From Baseline in the Patient-reported Convenience Subscale Using the TSQM v1.4
Description	The convenience subscale was scored as follows: questions 9 and 10 scored as 1(extremely difficult) to 7 (extremely easy), and question 11 scored as 1(extremely inconvenient) to 7 (extremely convenient). The scores of the domain were added together and an algorithm was used to create a score of 0 to 100. Higher scores indicated greater satisfaction. A positive change from baseline indicates improvement.
Time Frame	Baseline, Month 6

Outcome Measure Data

Analysis Population Description

This analysis was conducted using the Full Analysis Set. The Full Analysis Set comprised all randomized patients to whom study medication was assigned. Patients with both baseline and 6 month assessments were included in this analysis.

Arm/Group Title	Fingolimod	Multiple Sclerosis Disease Modifying Treatments (MS DMTs)
Arm/Group Description	Patients randomized in this arm received Fingolimod 0.5 mg/day oral capsule for 6 months core period.	Patients randomized in this arm received selected Standard MS DMT such as Interferon beta-1b or Interferon beta-1a or Glatiramer acetate for 6 months. An open-label extension of up to 3 months of treatment with fingolimod was to be available for patients in the DMT arm who successfully completed all study visits.
Measure Participants	718	222
Mean (Standard Deviation) [units on a scale]	41.8 (22.85)	1.5 (18.33)

8. Secondary Outcome

Title	Change From Baseline in Patient-reported Health-related Quality-of-life Using the Short Form Health Survey v2 Standard (SF-36 v2)
Description	The SF-36v2 is a validated health-related quality of life instrument used in numerous disease states, including MS. It is a self-administered survey that measures 8 domains of health including: physical functioning, role limitations due to physical health, bodily pain, general health perceptions, vitality, social functioning, role limitations due to emotional problems and general mental health. Additionally, two summary scale scores can be calculated: the Physical Component Summary (PCS) and the Mental Component Summary (MCS). If half or more questions within a domain were answered, then a score was calculated for that domain. Otherwise, the patient score for that domain was set to missing. If the patient was missing any 1 of the 8 scale scores, then the physical and mental component scores were set to missing. An algorithm was used to create a score from 0 to 100 for each domain score and component score. A positive change from baseline indicates improvement.
Time Frame	Baseline, Month 6

Outcome Measure Data

Analysis Population Description

This analysis was conducted using the Full Analysis Set. The Full Analysis Set comprised all randomized patients to whom study medication was assigned. Patients with both baseline and 6 month assessments were included in this analysis. Missing values were imputed using the Last Observation Carried Forward (LOCF) method.

Arm/Group Title	Fingolimod	Multiple Sclerosis Disease Modifying Treatments (MS DMTs)
Arm/Group Description	Patients randomized in this arm received Fingolimod 0.5 mg/day oral capsule for 6 months core period.	Patients randomized in this arm received selected Standard MS DMT such as Interferon beta-1b or Interferon beta-1a or Glatiramer acetate for 6 months. An open-label extension of up to 3 months of treatment with fingolimod was to be available for patients in the DMT arm who successfully completed all study visits.
Measure Participants	789	263
Physical Function (n=745,226)	1.5 (7.96)	0.4 (7.03)
Role Limitations d/t Physical Health (n=742,226)	2.8 (9.65)	1.2 (8.51)
Bodily Pain (n=742,226)	2.0 (9.7)	-0.3 (8.38)
General Health Perceptions (n=737,224)	0.8 (8.29)	-0.3 (7.24)
Vitality (n=745,227)	2.8 (8.88)	0.6 (7.73)
Social Functioning (n=747,227)	2.6 (10.31)	0.8 (10.61)
Role Limitation d/t Emotional Problems (n=745,226)	1.6 (12.48)	-0.6 (11.51)
General Mental Health (n=745,227)	2.2 (9.62)	0.3 (9.37)
Physical Component Summary Scale (n=724,222)	1.7 (7.41)	0.3 (6.48)
Mental Component Summary Scale (n=724,222)	2.3 (10.03)	0.2 (9.62)

9. Secondary Outcome

Title	Change From Baseline in Patient-reported Depression Using the Beck Depression Inventory (BDI-II)
Description	The Beck Depression Inventory (BDI-II) is a 21-question multiple-choice self-report inventory. Each item is scored from 0 to 3. The questions in the BDI-II refer to how the patient has been feeling over the past two weeks specifically. The BDI-II total score was calculated by summing the 21 item scores. Final scores ranged from 0 to 63 where higher scores indicated more severe depression. If no more than 20% of the items were missing, the total score was the product of the mean response of the non-missing items and the total number of items. If more than 20% of all items were missing, the total score was set to missing. A negative change indicates improvement.
Time Frame	Baseline, Month 3, Month 6

Outcome Measure Data

Analysis Population Description

This analysis was conducted using the Full Analysis Set. The Full Analysis Set comprised all randomized patients to whom study medication was assigned. Patients with baseline to 3 month assessments and/or baseline to 6 month assessments were included in this analysis.

Arm/Group Title	Fingolimod	Multiple Sclerosis Disease Modifying Treatments (MS DMTs)
Arm/Group Description	Patients randomized in this arm received Fingolimod 0.5 mg/day oral capsule for 6 months core period.	Patients randomized in this arm received selected Standard MS DMT such as Interferon beta-1b or Interferon beta-1a or Glatiramer acetate for 6 months. An open-label extension of up to 3 months of treatment with fingolimod was to be available for patients in the DMT arm who successfully completed all study visits.
Measure Participants	789	263
Change from Baseline to Month 3 (n=748,236)	-3.2 (7.17)	-0.8 (6.57)
Change from Baseline to Month 6 (n=709,223)	-3.4 (7.64)	-0.6 (6.76)

10. Secondary Outcome

Title	Physician-reported Clinical Global Impression of Improvement (CGI-I)
Description	The CGI-I is a rating scale allowing a physician-reported global evaluation of the subject's improvement over time. The Investigator assessed the subject's clinical change relative to the symptoms at baseline on the CGI-I, a seven-point scale, with rating as follows: 1=Very much improved, 2=Much improved, 3=Minimally improved, 4=No change, 5=Minimally worse, 6=Much worse, 7=Very much worse. The assessments were completed at Month 3 and Month 6. A lower score indicates improvement.
Time Frame	Month 3, Month 6

Outcome Measure Data

Analysis Population Description

This analysis was conducted using the Full Analysis Set. The Full Analysis Set comprised all randomized patients to whom study medication was assigned. Patients with month 3 and month 6 assessments were included in this analysis. Missing values were imputed using the Last Observation Carried Forward (LOCF) method.

Arm/Group Title	Fingolimod	Multiple Sclerosis Disease Modifying Treatments (MS DMTs)
Arm/Group Description	Patients randomized in this arm received Fingolimod 0.5 mg/day oral capsule for 6 months core period.	Patients randomized in this arm received selected Standard MS DMT such as Interferon beta-1b or Interferon beta-1a or Glatiramer acetate for 6 months. An open-label extension of up to 3 months of treatment with fingolimod was to be available for patients in the DMT arm who successfully completed all study visits.
Measure Participants	789	263
Month 3 (n=758,242)	3.4 (1.02)	3.9 (0.72)
Month 6 (n=727,228)	3.2 (1.11)	3.9 (0.62)

Adverse Events

Adverse Event Reporting Description	In this analysis, patients with all (serious and non-serious) adverse events, serious adverse events and death were reported.
Arm/Group Title	Fingolimod		Standard MS DMT		Fingolimod Extension Phase
Arm/Group Description	Patients randomized in this arm received Fingolimod 0.5 mg/day oral capsule for 6 months core period.		Patients randomized in this arm received selected Standard MS DMT such as Interferon beta-1b or Interferon beta-1a or Glatiramer acetate for 6 months.		An open-label extension of up to 3 months of treatment with fingolimod was to be available for patients in the DMT arm who successfully completed all study visits.
All Cause Mortality
	Fingolimod		Standard MS DMT		Fingolimod Extension Phase
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Fingolimod		Standard MS DMT		Fingolimod Extension Phase
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	31/783 (4%)		5/245 (2%)		7/193 (3.6%)
Blood and lymphatic system disorders
Lymphopenia	2/783 (0.3%)		0/245 (0%)		0/193 (0%)
Cardiac disorders
Bradycardia	1/783 (0.1%)		0/245 (0%)		0/193 (0%)
Palpitations	1/783 (0.1%)		0/245 (0%)		0/193 (0%)
Pericardial effusion	1/783 (0.1%)		0/245 (0%)		0/193 (0%)
Endocrine disorders
Basedow's disease	1/783 (0.1%)		0/245 (0%)		0/193 (0%)
Hyperthyroidism	1/783 (0.1%)		0/245 (0%)		0/193 (0%)
Eye disorders
Optic neuritis	1/783 (0.1%)		0/245 (0%)		0/193 (0%)
Gastrointestinal disorders
Abdominal pain	1/783 (0.1%)		0/245 (0%)		0/193 (0%)
Diarrhoea	0/783 (0%)		0/245 (0%)		1/193 (0.5%)
Gastric ileus	0/783 (0%)		0/245 (0%)		1/193 (0.5%)
Nausea	0/783 (0%)		0/245 (0%)		1/193 (0.5%)
Small intestinal obstruction	0/783 (0%)		0/245 (0%)		1/193 (0.5%)
General disorders
Chest discomfort	1/783 (0.1%)		0/245 (0%)		0/193 (0%)
Chest pain	1/783 (0.1%)		0/245 (0%)		1/193 (0.5%)
Chills	0/783 (0%)		0/245 (0%)		1/193 (0.5%)
Disease progression	1/783 (0.1%)		0/245 (0%)		0/193 (0%)
Non-cardiac chest pain	2/783 (0.3%)		0/245 (0%)		0/193 (0%)
Oedema peripheral	1/783 (0.1%)		0/245 (0%)		0/193 (0%)
Pain	0/783 (0%)		0/245 (0%)		1/193 (0.5%)
Pyrexia	0/783 (0%)		0/245 (0%)		1/193 (0.5%)
Hepatobiliary disorders
Cholecystitis chronic	0/783 (0%)		1/245 (0.4%)		0/193 (0%)
Cholelithiasis	1/783 (0.1%)		1/245 (0.4%)		0/193 (0%)
Immune system disorders
Anaphylactic reaction	1/783 (0.1%)		0/245 (0%)		0/193 (0%)
Infections and infestations
Appendicitis	1/783 (0.1%)		0/245 (0%)		0/193 (0%)
Gastroenteritis	0/783 (0%)		0/245 (0%)		1/193 (0.5%)
Kidney infection	1/783 (0.1%)		0/245 (0%)		0/193 (0%)
Pneumonia	1/783 (0.1%)		0/245 (0%)		0/193 (0%)
Upper respiratory tract infection	0/783 (0%)		1/245 (0.4%)		0/193 (0%)
Urinary tract infection	1/783 (0.1%)		0/245 (0%)		0/193 (0%)
Urosepsis	1/783 (0.1%)		0/245 (0%)		0/193 (0%)
Viral infection	0/783 (0%)		0/245 (0%)		1/193 (0.5%)
Injury, poisoning and procedural complications
Brain contusion	0/783 (0%)		1/245 (0.4%)		0/193 (0%)
Fall	0/783 (0%)		1/245 (0.4%)		0/193 (0%)
Overdose	1/783 (0.1%)		0/245 (0%)		0/193 (0%)
Investigations
Blood pressure increased	1/783 (0.1%)		0/245 (0%)		0/193 (0%)
Metabolism and nutrition disorders
Dehydration	1/783 (0.1%)		0/245 (0%)		0/193 (0%)
Musculoskeletal and connective tissue disorders
Osteoarthritis	1/783 (0.1%)		0/245 (0%)		0/193 (0%)
Nervous system disorders
Balance disorder	0/783 (0%)		1/245 (0.4%)		0/193 (0%)
Headache	0/783 (0%)		0/245 (0%)		1/193 (0.5%)
Metabolic encephalopathy	0/783 (0%)		0/245 (0%)		1/193 (0.5%)
Migraine	2/783 (0.3%)		0/245 (0%)		0/193 (0%)
Multiple sclerosis relapse	5/783 (0.6%)		2/245 (0.8%)		0/193 (0%)
Syncope	1/783 (0.1%)		0/245 (0%)		0/193 (0%)
Psychiatric disorders
Psychotic disorder	1/783 (0.1%)		0/245 (0%)		0/193 (0%)
Schizophrenia, paranoid type	1/783 (0.1%)		0/245 (0%)		0/193 (0%)
Suicidal ideation	0/783 (0%)		0/245 (0%)		1/193 (0.5%)
Renal and urinary disorders
Renal failure acute	1/783 (0.1%)		0/245 (0%)		0/193 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	1/783 (0.1%)		0/245 (0%)		0/193 (0%)
Pleural effusion	1/783 (0.1%)		0/245 (0%)		0/193 (0%)
Skin and subcutaneous tissue disorders
Dermatitis	1/783 (0.1%)		0/245 (0%)		0/193 (0%)
Vascular disorders
Hypertension	0/783 (0%)		0/245 (0%)		1/193 (0.5%)
Hypotension	1/783 (0.1%)		0/245 (0%)		0/193 (0%)
Other (Not Including Serious) Adverse Events
	Fingolimod		Standard MS DMT		Fingolimod Extension Phase
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	316/783 (40.4%)		51/245 (20.8%)		56/193 (29%)
Gastrointestinal disorders
Diarrhoea	41/783 (5.2%)		4/245 (1.6%)		3/193 (1.6%)
Nausea	48/783 (6.1%)		5/245 (2%)		11/193 (5.7%)
General disorders
Fatigue	90/783 (11.5%)		14/245 (5.7%)		10/193 (5.2%)
Infections and infestations
Nasopharyngitis	43/783 (5.5%)		13/245 (5.3%)		7/193 (3.6%)
Upper respiratory tract infection	51/783 (6.5%)		8/245 (3.3%)		9/193 (4.7%)
Nervous system disorders
Dizziness	50/783 (6.4%)		7/245 (2.9%)		7/193 (3.6%)
Headache	97/783 (12.4%)		8/245 (3.3%)		19/193 (9.8%)
Vascular disorders
Hypertension	43/783 (5.5%)		4/245 (1.6%)		6/193 (3.1%)

Limitations/Caveats

[Not Specified]

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 (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.