Trial Outcomes & Findings for Efficacy and Safety of FTY720 in Patients With Relapsing Multiple Sclerosis (NCT NCT00333138)
NCT ID: NCT00333138
Last Updated: 2017-09-15
Results Overview
Total number of post-baseline Gd-enhanced lesions is calculated as a sum of all Gd-enhanced lesions seen on post-baseline scans per visit. Real (not per slice) lesions are counted in this analysis.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
281 participants
Primary outcome timeframe
Month 6 (Core)
Results posted on
2017-09-15
Participant Flow
Participant milestones
| Measure |
Placebo
Core study: patients received placebo, once daily for 6 months. Extension: In dose-blind period patients were re-randomized into either fingolimod 1.25 mg or 5.0 mg once per day for 6-15 months. In open-label period patients received fingolimod 1.25 mg once per day for 15 to 24 months. Later, all patients converted to fingolimod 0.5 mg, once daily for rest of the study participation.
|
Fingolimod (FTY720) 1.25 mg/Day
Core study: patients received fingolimod 1.25 mg, once daily for 6 months. Extension: In dose -blind period and open label, fingolimod 1.25 mg once daily for 9-18 months (6 months to 24 months). Later, all patients converted to fingolimod 0.5 mg, once daily for rest of the study participation.
|
Fingolimod (FTY720) 5.0 mg/Day
Core study: patients received fingolimod 5.0 mg, once daily for 6 months. Extension: In dose-blind period fingolimod 5.0 mg once daily for 6-15 months. For open-label phase 1.25mg once daily for 15 to 24 months. Later, all patients converted to fingolimod 0.5 mg, once daily for rest of the study participation.
|
|---|---|---|---|
|
Core Study (6 Months)
STARTED
|
93
|
94
|
94
|
|
Core Study (6 Months)
COMPLETED
|
86
|
88
|
82
|
|
Core Study (6 Months)
NOT COMPLETED
|
7
|
6
|
12
|
|
Extension Study (Month6 to End of Study)
STARTED
|
83
|
87
|
80
|
|
Extension Study (Month6 to End of Study)
COMPLETED
|
40
|
45
|
37
|
|
Extension Study (Month6 to End of Study)
NOT COMPLETED
|
43
|
42
|
43
|
Reasons for withdrawal
| Measure |
Placebo
Core study: patients received placebo, once daily for 6 months. Extension: In dose-blind period patients were re-randomized into either fingolimod 1.25 mg or 5.0 mg once per day for 6-15 months. In open-label period patients received fingolimod 1.25 mg once per day for 15 to 24 months. Later, all patients converted to fingolimod 0.5 mg, once daily for rest of the study participation.
|
Fingolimod (FTY720) 1.25 mg/Day
Core study: patients received fingolimod 1.25 mg, once daily for 6 months. Extension: In dose -blind period and open label, fingolimod 1.25 mg once daily for 9-18 months (6 months to 24 months). Later, all patients converted to fingolimod 0.5 mg, once daily for rest of the study participation.
|
Fingolimod (FTY720) 5.0 mg/Day
Core study: patients received fingolimod 5.0 mg, once daily for 6 months. Extension: In dose-blind period fingolimod 5.0 mg once daily for 6-15 months. For open-label phase 1.25mg once daily for 15 to 24 months. Later, all patients converted to fingolimod 0.5 mg, once daily for rest of the study participation.
|
|---|---|---|---|
|
Core Study (6 Months)
Adverse Event
|
4
|
5
|
8
|
|
Core Study (6 Months)
Withdrawal by Subject
|
1
|
1
|
2
|
|
Core Study (6 Months)
Lack of Efficacy
|
1
|
0
|
0
|
|
Core Study (6 Months)
Protocol Violation
|
1
|
0
|
1
|
|
Core Study (6 Months)
Laboratory abnormality
|
0
|
0
|
1
|
|
Extension Study (Month6 to End of Study)
Abnormal laboratory value
|
3
|
2
|
2
|
|
Extension Study (Month6 to End of Study)
Administrative problems
|
1
|
1
|
2
|
|
Extension Study (Month6 to End of Study)
Adverse Event
|
15
|
19
|
15
|
|
Extension Study (Month6 to End of Study)
Protocol Violation
|
0
|
0
|
3
|
|
Extension Study (Month6 to End of Study)
Withdrawal by Subject
|
14
|
13
|
14
|
|
Extension Study (Month6 to End of Study)
Lack of Efficacy
|
7
|
4
|
7
|
|
Extension Study (Month6 to End of Study)
Patient no longer required study drug
|
2
|
1
|
0
|
|
Extension Study (Month6 to End of Study)
Lost to Follow-up
|
1
|
1
|
0
|
|
Extension Study (Month6 to End of Study)
Death
|
0
|
1
|
0
|
Baseline Characteristics
Efficacy and Safety of FTY720 in Patients With Relapsing Multiple Sclerosis
Baseline characteristics by cohort
| Measure |
Placebo
n=93 Participants
Core study: patients received placebo, once daily for 6 months. Extension: In dose-blind period patients were re-randomized into either fingolimod 1.25 mg or 5.0 mg once per day for 6-15 months. In open-label period patients received fingolimod 1.25 mg once per day for 15 to 24 months. Later, all patients converted to fingolimod 0.5 mg, once daily for rest of the study participation.
|
Fingolimod (FTY720) 1.25 mg/Day
n=94 Participants
Core study: patients received fingolimod 1.25 mg, once daily for 6 months. Extension: In dose -blind period and open label, fingolimod 1.25 mg once daily for 9-18 months (6 months to 24 months). Later, all patients converted to fingolimod 0.5 mg, once daily for rest of the study participation.
|
Fingolimod (FTY720) 5.0 mg/Day
n=94 Participants
Core study: patients received fingolimod 5.0 mg, once daily for 6 months. Extension: In dose-blind period fingolimod 5.0 mg once daily for 6-15 months. For open-label phase 1.25mg once daily for 15 to 24 months. Later, all patients converted to fingolimod 0.5 mg, once daily for rest of the study participation.
|
Total
n=281 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
37.0 Years
STANDARD_DEVIATION 8.80 • n=5 Participants
|
38.1 Years
STANDARD_DEVIATION 9.54 • n=7 Participants
|
38.3 Years
STANDARD_DEVIATION 10.51 • n=5 Participants
|
37.8 Years
STANDARD_DEVIATION 9.63 • n=4 Participants
|
|
Sex: Female, Male
Female
|
62 Participants
n=5 Participants
|
71 Participants
n=7 Participants
|
66 Participants
n=5 Participants
|
199 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
31 Participants
n=5 Participants
|
23 Participants
n=7 Participants
|
28 Participants
n=5 Participants
|
82 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Month 6 (Core)Population: All randomized patients who received at least 1 dose of study drug during the core study were included in the ITT population. Number of patients with T1 information recorded at scan were included in the analysis.
Total number of post-baseline Gd-enhanced lesions is calculated as a sum of all Gd-enhanced lesions seen on post-baseline scans per visit. Real (not per slice) lesions are counted in this analysis.
Outcome measures
| Measure |
Placebo
n=83 Participants
Core study: patients received placebo, once daily for 6 months. Extension: In dose-blind period patients were re-randomized into either fingolimod 1.25 mg or 5.0 mg once per day for 6-15 months. In open-label period patients received fingolimod 1.25 mg once per day for 15 to 24 months. Later, all patients converted to fingolimod 0.5 mg, once daily for rest of the study participation.
|
Fingolimod (FTY720) 1.25 mg/Day
n=90 Participants
Core study: patients received fingolimod 1.25 mg, once daily for 6 months. Extension: In dose -blind period and open label, fingolimod 1.25 mg once daily for 9-18 months (6 months to 24 months). Later, all patients converted to fingolimod 0.5 mg, once daily for rest of the study participation.
|
Fingolimod (FTY720) 5.0 mg/Day
n=87 Participants
Core study: patients received fingolimod 5.0 mg, once daily for 6 months. Extension: In dose-blind period fingolimod 5.0 mg once daily for 6-15 months. For open-label phase 1.25mg once daily for 15 to 24 months. Later, all patients converted to fingolimod 0.5 mg, once daily for rest of the study participation.
|
|---|---|---|---|
|
Mean Number of Gadolinium (Gd)-Enhanced T1-weighted Lesions at Month 6 (Core)
|
2.3 GD- enhanced T1 lesions
Standard Deviation 4.23
|
1.4 GD- enhanced T1 lesions
Standard Deviation 5.69
|
0.4 GD- enhanced T1 lesions
Standard Deviation 0.82
|
PRIMARY outcome
Timeframe: Month 12 (extension)Population: All randomized patients who received at least 1 dose of study drug during the core study were included in the ITT population. Number of patients with T1 information recorded at scan were included in the analysis.
Total number of post-baseline Gd-enhanced lesions is calculated as a sum of all Gd-enhanced lesions seen on post-baseline scans per visit. Real (not per slice) lesions are counted in this analysis.
Outcome measures
| Measure |
Placebo
n=72 Participants
Core study: patients received placebo, once daily for 6 months. Extension: In dose-blind period patients were re-randomized into either fingolimod 1.25 mg or 5.0 mg once per day for 6-15 months. In open-label period patients received fingolimod 1.25 mg once per day for 15 to 24 months. Later, all patients converted to fingolimod 0.5 mg, once daily for rest of the study participation.
|
Fingolimod (FTY720) 1.25 mg/Day
n=77 Participants
Core study: patients received fingolimod 1.25 mg, once daily for 6 months. Extension: In dose -blind period and open label, fingolimod 1.25 mg once daily for 9-18 months (6 months to 24 months). Later, all patients converted to fingolimod 0.5 mg, once daily for rest of the study participation.
|
Fingolimod (FTY720) 5.0 mg/Day
n=71 Participants
Core study: patients received fingolimod 5.0 mg, once daily for 6 months. Extension: In dose-blind period fingolimod 5.0 mg once daily for 6-15 months. For open-label phase 1.25mg once daily for 15 to 24 months. Later, all patients converted to fingolimod 0.5 mg, once daily for rest of the study participation.
|
|---|---|---|---|
|
Mean Number of Gadolinium (Gd)-Enhanced T1-weighted Lesions at Month 12
|
0.4 GD- enhanced T1 lesions
Standard Deviation 0.95
|
1.0 GD- enhanced T1 lesions
Standard Deviation 5.81
|
0.2 GD- enhanced T1 lesions
Standard Deviation 0.47
|
PRIMARY outcome
Timeframe: Month 60 (extension)Population: All randomized patients who received at least 1 dose of study drug during the core study were included in the ITT population. Number of patients with T1 information recorded at scan were included in the analysis.
Total number of post-baseline Gd-enhanced lesions is calculated as a sum of all Gd-enhanced lesions seen on post-baseline scans per visit. Real (not per slice) lesions are counted in this analysis.
Outcome measures
| Measure |
Placebo
n=45 Participants
Core study: patients received placebo, once daily for 6 months. Extension: In dose-blind period patients were re-randomized into either fingolimod 1.25 mg or 5.0 mg once per day for 6-15 months. In open-label period patients received fingolimod 1.25 mg once per day for 15 to 24 months. Later, all patients converted to fingolimod 0.5 mg, once daily for rest of the study participation.
|
Fingolimod (FTY720) 1.25 mg/Day
n=49 Participants
Core study: patients received fingolimod 1.25 mg, once daily for 6 months. Extension: In dose -blind period and open label, fingolimod 1.25 mg once daily for 9-18 months (6 months to 24 months). Later, all patients converted to fingolimod 0.5 mg, once daily for rest of the study participation.
|
Fingolimod (FTY720) 5.0 mg/Day
n=44 Participants
Core study: patients received fingolimod 5.0 mg, once daily for 6 months. Extension: In dose-blind period fingolimod 5.0 mg once daily for 6-15 months. For open-label phase 1.25mg once daily for 15 to 24 months. Later, all patients converted to fingolimod 0.5 mg, once daily for rest of the study participation.
|
|---|---|---|---|
|
Mean Number of Gadolinium (Gd)-Enhanced T1-weighted Lesions at Month 60
|
0.2 GD- enhanced T1 lesions
Standard Deviation 0.7
|
0.2 GD- enhanced T1 lesions
Standard Deviation 0.92
|
0.1 GD- enhanced T1 lesions
Standard Deviation 0.55
|
PRIMARY outcome
Timeframe: Last observation (Up to 80 months in average)Population: All randomized patients who received at least 1 dose of study drug during the core study were included in the ITT population. Number of patients with T1 information recorded at scan were included in the analysis.
Total number of post-baseline Gd-enhanced lesions is calculated as a sum of all Gd-enhanced lesions seen on post-baseline scans per visit. Real (not per slice) lesions are counted in this analysis. The last observation was the last observation available for each patient which ranged from 1 to 2801 days
Outcome measures
| Measure |
Placebo
n=92 Participants
Core study: patients received placebo, once daily for 6 months. Extension: In dose-blind period patients were re-randomized into either fingolimod 1.25 mg or 5.0 mg once per day for 6-15 months. In open-label period patients received fingolimod 1.25 mg once per day for 15 to 24 months. Later, all patients converted to fingolimod 0.5 mg, once daily for rest of the study participation.
|
Fingolimod (FTY720) 1.25 mg/Day
n=93 Participants
Core study: patients received fingolimod 1.25 mg, once daily for 6 months. Extension: In dose -blind period and open label, fingolimod 1.25 mg once daily for 9-18 months (6 months to 24 months). Later, all patients converted to fingolimod 0.5 mg, once daily for rest of the study participation.
|
Fingolimod (FTY720) 5.0 mg/Day
n=92 Participants
Core study: patients received fingolimod 5.0 mg, once daily for 6 months. Extension: In dose-blind period fingolimod 5.0 mg once daily for 6-15 months. For open-label phase 1.25mg once daily for 15 to 24 months. Later, all patients converted to fingolimod 0.5 mg, once daily for rest of the study participation.
|
|---|---|---|---|
|
Mean Number of Gadolinium (Gd)-Enhanced T1-weighted Lesions at End of Study
|
0.8 GD- enhanced T1 lesions
Standard Deviation 2.87
|
0.4 GD- enhanced T1 lesions
Standard Deviation 1.39
|
0.5 GD- enhanced T1 lesions
Standard Deviation 1.65
|
SECONDARY outcome
Timeframe: Baseline, Months 6 (core), 12, 60 and Last Observation (up to 80 months in average)Population: All randomized patients who received at least 1 dose of study drug during the core study were included in the ITT population. Number of patients with T1 information recorded at scan were included in the analysis. The "n" in each category indicates number of patients wih information recorded at scan
A patient was defined as free of lesions if s/he had zero lesions. The last observation was the last observation available for each patient which ranged from 1 to 2801 days
Outcome measures
| Measure |
Placebo
n=93 Participants
Core study: patients received placebo, once daily for 6 months. Extension: In dose-blind period patients were re-randomized into either fingolimod 1.25 mg or 5.0 mg once per day for 6-15 months. In open-label period patients received fingolimod 1.25 mg once per day for 15 to 24 months. Later, all patients converted to fingolimod 0.5 mg, once daily for rest of the study participation.
|
Fingolimod (FTY720) 1.25 mg/Day
n=94 Participants
Core study: patients received fingolimod 1.25 mg, once daily for 6 months. Extension: In dose -blind period and open label, fingolimod 1.25 mg once daily for 9-18 months (6 months to 24 months). Later, all patients converted to fingolimod 0.5 mg, once daily for rest of the study participation.
|
Fingolimod (FTY720) 5.0 mg/Day
n=94 Participants
Core study: patients received fingolimod 5.0 mg, once daily for 6 months. Extension: In dose-blind period fingolimod 5.0 mg once daily for 6-15 months. For open-label phase 1.25mg once daily for 15 to 24 months. Later, all patients converted to fingolimod 0.5 mg, once daily for rest of the study participation.
|
|---|---|---|---|
|
Percentage of Participants Free of T1-weighted Lesions
Baseline (Core) n=93, 92, 93
|
49.5 percentage of participants
|
52.2 percentage of participants
|
48.4 percentage of participants
|
|
Percentage of Participants Free of T1-weighted Lesions
Month 6 (Core) n= 83, 90, 87
|
47.0 percentage of participants
|
76.7 percentage of participants
|
78.2 percentage of participants
|
|
Percentage of Participants Free of T1-weighted Lesions
Month 12 (Extension) n= 72, 77, 71
|
79.2 percentage of participants
|
83.1 percentage of participants
|
88.7 percentage of participants
|
|
Percentage of Participants Free of T1-weighted Lesions
Month 60 (Extension) n= 45, 49, 44
|
91.1 percentage of participants
|
91.8 percentage of participants
|
93.2 percentage of participants
|
|
Percentage of Participants Free of T1-weighted Lesions
Last observation (Extension) n= 92, 93, 92
|
81.5 percentage of participants
|
83.9 percentage of participants
|
83.7 percentage of participants
|
SECONDARY outcome
Timeframe: Month 6 and 12, 60, last observation (up to 80 months in average)Population: All randomized patients who received at least 1 dose of study drug during core study were included in the ITT population. The "n" number of patients with T2 and T1 information recorded at scan
A patient was defined as free of lesions if s/he had zero lesions. The sum of all new T2-weighted lesions at Month 1 to last observation was zero (the sum is missing if one of the assessments was missing). New T2 lesions at a specific visit were assessed relative to the previous visit scan. Exception: new T2 lesions at Month 24 were assessed relative to Month 12. The last observation was the last observation available for each patient which ranged from 1 to 2801 days
Outcome measures
| Measure |
Placebo
n=93 Participants
Core study: patients received placebo, once daily for 6 months. Extension: In dose-blind period patients were re-randomized into either fingolimod 1.25 mg or 5.0 mg once per day for 6-15 months. In open-label period patients received fingolimod 1.25 mg once per day for 15 to 24 months. Later, all patients converted to fingolimod 0.5 mg, once daily for rest of the study participation.
|
Fingolimod (FTY720) 1.25 mg/Day
n=94 Participants
Core study: patients received fingolimod 1.25 mg, once daily for 6 months. Extension: In dose -blind period and open label, fingolimod 1.25 mg once daily for 9-18 months (6 months to 24 months). Later, all patients converted to fingolimod 0.5 mg, once daily for rest of the study participation.
|
Fingolimod (FTY720) 5.0 mg/Day
n=94 Participants
Core study: patients received fingolimod 5.0 mg, once daily for 6 months. Extension: In dose-blind period fingolimod 5.0 mg once daily for 6-15 months. For open-label phase 1.25mg once daily for 15 to 24 months. Later, all patients converted to fingolimod 0.5 mg, once daily for rest of the study participation.
|
|---|---|---|---|
|
Percentage of Patients Free of Gd-enhanced T1-weighted and New T2- Weighted Lesions by Visit
Last observation (Extension) n=92, 93,90
|
72.8 percentage of paticipants
|
76.3 percentage of paticipants
|
78.9 percentage of paticipants
|
|
Percentage of Patients Free of Gd-enhanced T1-weighted and New T2- Weighted Lesions by Visit
Month 6 (Core), n= 80, 87, 83
|
47.5 percentage of paticipants
|
77.0 percentage of paticipants
|
80.7 percentage of paticipants
|
|
Percentage of Patients Free of Gd-enhanced T1-weighted and New T2- Weighted Lesions by Visit
Month 12 (Extension) n=70, 77, 70
|
57.1 percentage of paticipants
|
67.5 percentage of paticipants
|
72.9 percentage of paticipants
|
|
Percentage of Patients Free of Gd-enhanced T1-weighted and New T2- Weighted Lesions by Visit
Month 60 (Extension) n=45, 49, 43
|
88.9 percentage of paticipants
|
87.8 percentage of paticipants
|
83.7 percentage of paticipants
|
SECONDARY outcome
Timeframe: (Core) Month 6 and (Extension) 12, 60, last observation (up to 80 months in average)Population: All randomized patients who received at least 1 dose of study drug during the core study were included in the ITT population. The "n" in each category indicates participants with T2 information recorded at specific timepoints
New T2 lesions at a specific visit were assessed relative to the previous visit scan. The total number of lesions (Month 1 to end of study) is calculated as the sum of the number of lesions at Months 1 to 6, Month 12, Month 60 and last observation. The last observation was the last observation available for each patient which ranged from 1 to 2801 days
Outcome measures
| Measure |
Placebo
n=93 Participants
Core study: patients received placebo, once daily for 6 months. Extension: In dose-blind period patients were re-randomized into either fingolimod 1.25 mg or 5.0 mg once per day for 6-15 months. In open-label period patients received fingolimod 1.25 mg once per day for 15 to 24 months. Later, all patients converted to fingolimod 0.5 mg, once daily for rest of the study participation.
|
Fingolimod (FTY720) 1.25 mg/Day
n=94 Participants
Core study: patients received fingolimod 1.25 mg, once daily for 6 months. Extension: In dose -blind period and open label, fingolimod 1.25 mg once daily for 9-18 months (6 months to 24 months). Later, all patients converted to fingolimod 0.5 mg, once daily for rest of the study participation.
|
Fingolimod (FTY720) 5.0 mg/Day
n=94 Participants
Core study: patients received fingolimod 5.0 mg, once daily for 6 months. Extension: In dose-blind period fingolimod 5.0 mg once daily for 6-15 months. For open-label phase 1.25mg once daily for 15 to 24 months. Later, all patients converted to fingolimod 0.5 mg, once daily for rest of the study participation.
|
|---|---|---|---|
|
Mean Number of New T2-weighted Lesions
Month 60 (Extension) n=45, 50, 43
|
0.4 GD enhanced T2 lesions
Standard Deviation 1.25
|
0.5 GD enhanced T2 lesions
Standard Deviation 1.36
|
0.3 GD enhanced T2 lesions
Standard Deviation 0.97
|
|
Mean Number of New T2-weighted Lesions
Month 6 (Core), n= 82,88, 84
|
1.0 GD enhanced T2 lesions
Standard Deviation 2.37
|
0.5 GD enhanced T2 lesions
Standard Deviation 2.07
|
0.1 GD enhanced T2 lesions
Standard Deviation 0.34
|
|
Mean Number of New T2-weighted Lesions
Month 12 (Extension) n=71, 79, 71
|
0.8 GD enhanced T2 lesions
Standard Deviation 1.41
|
1.4 GD enhanced T2 lesions
Standard Deviation 5.56
|
0.6 GD enhanced T2 lesions
Standard Deviation 1.10
|
|
Mean Number of New T2-weighted Lesions
Last observation (Extension) n=92, 93, 91
|
0.7 GD enhanced T2 lesions
Standard Deviation 1.99
|
0.6 GD enhanced T2 lesions
Standard Deviation 1.51
|
0.5 GD enhanced T2 lesions
Standard Deviation 1.64
|
SECONDARY outcome
Timeframe: (Core) Month 6 and (Extension) 12, 60, last observation (up to 80 months in average)Population: All randomized patients who received at least 1 dose of study drug during the core study were included in the ITT population. The "n" in each category indicates participants with T2 information recorded at specific timepoints
Volume of total T2-weighted lesions by visit were summarized. The last observation was the last observation available for each patient which ranged from 1 to 2801 days
Outcome measures
| Measure |
Placebo
n=93 Participants
Core study: patients received placebo, once daily for 6 months. Extension: In dose-blind period patients were re-randomized into either fingolimod 1.25 mg or 5.0 mg once per day for 6-15 months. In open-label period patients received fingolimod 1.25 mg once per day for 15 to 24 months. Later, all patients converted to fingolimod 0.5 mg, once daily for rest of the study participation.
|
Fingolimod (FTY720) 1.25 mg/Day
n=94 Participants
Core study: patients received fingolimod 1.25 mg, once daily for 6 months. Extension: In dose -blind period and open label, fingolimod 1.25 mg once daily for 9-18 months (6 months to 24 months). Later, all patients converted to fingolimod 0.5 mg, once daily for rest of the study participation.
|
Fingolimod (FTY720) 5.0 mg/Day
n=94 Participants
Core study: patients received fingolimod 5.0 mg, once daily for 6 months. Extension: In dose-blind period fingolimod 5.0 mg once daily for 6-15 months. For open-label phase 1.25mg once daily for 15 to 24 months. Later, all patients converted to fingolimod 0.5 mg, once daily for rest of the study participation.
|
|---|---|---|---|
|
Volume of T2-weighted Lesions
Month 12 (Extension) n= 73, 79, 72
|
8264.1 mm^3
Standard Deviation 10121.43
|
10707.1 mm^3
Standard Deviation 14887.66
|
8363.2 mm^3
Standard Deviation 10694.82
|
|
Volume of T2-weighted Lesions
Month 60 (Extension) n=45, 50, 44
|
6698.3 mm^3
Standard Deviation 9569.98
|
9498.7 mm^3
Standard Deviation 9765.60
|
6626.9 mm^3
Standard Deviation 9146.01
|
|
Volume of T2-weighted Lesions
Month 6 (Core) n=85, 91, 87
|
9016.0 mm^3
Standard Deviation 10361.83
|
10084.6 mm^3
Standard Deviation 14774.16
|
8331.1 mm^3
Standard Deviation 10162.01
|
|
Volume of T2-weighted Lesions
Last observation (Extension) n=87, 91, 88
|
8757.2 mm^3
Standard Deviation 10127.01
|
10090.2 mm^3
Standard Deviation 13999.50
|
8061.8 mm^3
Standard Deviation 9003.47
|
SECONDARY outcome
Timeframe: Baseline to month 6, 12, 60 and Last observation (up to 80 months in average)Population: All randomized patients who received at least 1 dose of study drug during the core study were included in the ITT population. The "n" in each category indicates participants with T2 information recorded at specific timepoints
Change in volume of total T2-weighted lesions by visit were summarized. Negative values indicate improvement (reduction in lesion volume) and positive values worsening (increase in lesion volume). The last observation was the last observation available for each patient which ranged from 1 to 2801 days.
Outcome measures
| Measure |
Placebo
n=93 Participants
Core study: patients received placebo, once daily for 6 months. Extension: In dose-blind period patients were re-randomized into either fingolimod 1.25 mg or 5.0 mg once per day for 6-15 months. In open-label period patients received fingolimod 1.25 mg once per day for 15 to 24 months. Later, all patients converted to fingolimod 0.5 mg, once daily for rest of the study participation.
|
Fingolimod (FTY720) 1.25 mg/Day
n=94 Participants
Core study: patients received fingolimod 1.25 mg, once daily for 6 months. Extension: In dose -blind period and open label, fingolimod 1.25 mg once daily for 9-18 months (6 months to 24 months). Later, all patients converted to fingolimod 0.5 mg, once daily for rest of the study participation.
|
Fingolimod (FTY720) 5.0 mg/Day
n=94 Participants
Core study: patients received fingolimod 5.0 mg, once daily for 6 months. Extension: In dose-blind period fingolimod 5.0 mg once daily for 6-15 months. For open-label phase 1.25mg once daily for 15 to 24 months. Later, all patients converted to fingolimod 0.5 mg, once daily for rest of the study participation.
|
|---|---|---|---|
|
Change From Baseline in Volume of Total T2-weighted Lesions
Last observation (extension) n= 87, 89, 87
|
-178.86 mm^3
Standard Deviation 1884.904
|
-92.24 mm^3
Standard Deviation 3033.041
|
-907.48 mm^3
Standard Deviation 2997.668
|
|
Change From Baseline in Volume of Total T2-weighted Lesions
Month 6 (core) n=85, 89, 86
|
146.15 mm^3
Standard Deviation 1683.602
|
-115.81 mm^3
Standard Deviation 1031.799
|
-607.97 mm^3
Standard Deviation 1705.486
|
|
Change From Baseline in Volume of Total T2-weighted Lesions
Month 12 (extension) n=73, 77, 71
|
144.96 mm^3
Standard Deviation 1513.577
|
1.66 mm^3
Standard Deviation 1714.731
|
-513.35 mm^3
Standard Deviation 1943.338
|
|
Change From Baseline in Volume of Total T2-weighted Lesions
Month 60 (extension) n=45, 49, 43
|
-621.82 mm^3
Standard Deviation 1338.966
|
-204.09 mm^3
Standard Deviation 2238.182
|
-1429.98 mm^3
Standard Deviation 3928.944
|
SECONDARY outcome
Timeframe: Month 6,12,60 and Last observation (up to 80 months in average)Population: All randomized patients who received at least 1 dose of study drug during the core study were included in the ITT population. A patient at risk are those continuing in the study without an event before the specified timepoint The "n" denotes number of patients at risk.
The Expanded Disability Status Scale (EDSS) is a scale for assessing disability in 8 functional systems (visual, brain stem, pyramidal, cerebellar, sensory, bowel \& bladder, cerebral, other functions). An overall score ranging from 0 (normal) to 10 (death due to MS) is calculated. Disability progression was determined by the EDSS score based on the following criteria: One point increase from baseline in patients with baseline EDSS score from 0 to 5.0; or half a point increase in patients with baseline EDSS score of 5.5 or above. Percent of patients free of disability progression was calculated using the Kaplan-Meier method. The last observation was the last observation available for each patient which ranged from 1 to 2801 days
Outcome measures
| Measure |
Placebo
n=93 Participants
Core study: patients received placebo, once daily for 6 months. Extension: In dose-blind period patients were re-randomized into either fingolimod 1.25 mg or 5.0 mg once per day for 6-15 months. In open-label period patients received fingolimod 1.25 mg once per day for 15 to 24 months. Later, all patients converted to fingolimod 0.5 mg, once daily for rest of the study participation.
|
Fingolimod (FTY720) 1.25 mg/Day
n=94 Participants
Core study: patients received fingolimod 1.25 mg, once daily for 6 months. Extension: In dose -blind period and open label, fingolimod 1.25 mg once daily for 9-18 months (6 months to 24 months). Later, all patients converted to fingolimod 0.5 mg, once daily for rest of the study participation.
|
Fingolimod (FTY720) 5.0 mg/Day
n=94 Participants
Core study: patients received fingolimod 5.0 mg, once daily for 6 months. Extension: In dose-blind period fingolimod 5.0 mg once daily for 6-15 months. For open-label phase 1.25mg once daily for 15 to 24 months. Later, all patients converted to fingolimod 0.5 mg, once daily for rest of the study participation.
|
|---|---|---|---|
|
Time to Event Analysis: Kaplan Meier Estimates of Percentage of Relapse-free Patients
400 days (n=48, 63, 60)
|
0.62 percentage of participants
Interval 0.52 to 0.725
|
0.78 percentage of participants
Interval 0.699 to 0.871
|
0.79 percentage of participants
Interval 0.707 to 0.878
|
|
Time to Event Analysis: Kaplan Meier Estimates of Percentage of Relapse-free Patients
1400 days (n=29, 36, 35)
|
0.51 percentage of participants
Interval 0.399 to 0.619
|
0.63 percentage of participants
Interval 0.516 to 0.739
|
0.70 percentage of participants
Interval 0.594 to 0.802
|
|
Time to Event Analysis: Kaplan Meier Estimates of Percentage of Relapse-free Patients
1600 days (n=27, 34, 34)
|
0.51 percentage of participants
Interval 0.399 to 0.619
|
0.61 percentage of participants
Interval 0.496 to 0.724
|
0.68 percentage of participants
Interval 0.57 to 0.786
|
|
Time to Event Analysis: Kaplan Meier Estimates of Percentage of Relapse-free Patients
0 days (n=93,94,94)
|
1.00 percentage of participants
Interval 1.0 to 1.0
|
1.00 percentage of participants
Interval 1.0 to 1.0
|
1.00 percentage of participants
Interval 1.0 to 1.0
|
|
Time to Event Analysis: Kaplan Meier Estimates of Percentage of Relapse-free Patients
200 days (n=57, 73, 70)
|
0.69 percentage of participants
Interval 0.589 to 0.782
|
0.86 percentage of participants
Interval 0.786 to 0.929
|
0.86 percentage of participants
Interval 0.782 to 0.928
|
|
Time to Event Analysis: Kaplan Meier Estimates of Percentage of Relapse-free Patients
600 days (n=41, 57, 52)
|
0.58 percentage of participants
Interval 0.478 to 0.688
|
0.76 percentage of participants
Interval 0.669 to 0.849
|
0.78 percentage of participants
Interval 0.69 to 0.867
|
|
Time to Event Analysis: Kaplan Meier Estimates of Percentage of Relapse-free Patients
800 days (n=38, 48, 48)
|
0.55 percentage of participants
Interval 0.477 to 0.662
|
0.75 percentage of participants
Interval 0.652 to 0.838
|
0.75 percentage of participants
Interval 0.653 to 0.843
|
|
Time to Event Analysis: Kaplan Meier Estimates of Percentage of Relapse-free Patients
1000 days (n=35, 42, 45)
|
0.53 percentage of participants
Interval 0.416 to 0.634
|
0.70 percentage of participants
Interval 0.595 to 0.798
|
0.75 percentage of participants
Interval 0.653 to 0.843
|
|
Time to Event Analysis: Kaplan Meier Estimates of Percentage of Relapse-free Patients
1200 days (n=30, 38 40)
|
0.51 percentage of participants
Interval 0.399 to 0.619
|
0.66 percentage of participants
Interval 0.55 to 0.77
|
0.70 percentage of participants
Interval 0.594 to 0.802
|
|
Time to Event Analysis: Kaplan Meier Estimates of Percentage of Relapse-free Patients
1800 days (n=25, 33, 33)
|
0.51 percentage of participants
Interval 0.399 to 0.619
|
0.61 percentage of participants
Interval 0.496 to 0.724
|
0.68 percentage of participants
Interval 0.57 to 0.786
|
|
Time to Event Analysis: Kaplan Meier Estimates of Percentage of Relapse-free Patients
2000 days (n=23, 31, 31)
|
0.51 percentage of participants
Interval 0.399 to 0.619
|
0.59 percentage of participants
Interval 0.475 to 0.707
|
0.66 percentage of participants
Interval 0.545 to 0.769
|
|
Time to Event Analysis: Kaplan Meier Estimates of Percentage of Relapse-free Patients
2200 days (n=22, 28, 30)
|
0.49 percentage of participants
Interval 0.373 to 0.6
|
0.55 percentage of participants
Interval 0.433 to 0.673
|
0.66 percentage of participants
Interval 0.545 to 0.769
|
|
Time to Event Analysis: Kaplan Meier Estimates of Percentage of Relapse-free Patients
2400 days (n=21, 26, 27)
|
0.46 percentage of participants
Interval 0.348 to 0.581
|
0.55 percentage of participants
Interval 0.433 to 0.673
|
0.66 percentage of participants
Interval 0.545 to 0.769
|
|
Time to Event Analysis: Kaplan Meier Estimates of Percentage of Relapse-free Patients
2600 days (n=9, 12, 12)
|
0.44 percentage of participants
Interval 0.313 to 0.558
|
0.55 percentage of participants
Interval 0.433 to 0.673
|
0.66 percentage of participants
Interval 0.545 to 0.769
|
|
Time to Event Analysis: Kaplan Meier Estimates of Percentage of Relapse-free Patients
2880 days (n=0, 0, 0)
|
0 percentage of participants
Interval 0.0 to 0.0
|
0 percentage of participants
Interval 0.0 to 0.0
|
0 percentage of participants
Interval 0.0 to 0.0
|
SECONDARY outcome
Timeframe: Month 3 and 6Population: Pharmacokinetics population included all the patients who had sample collected and analysis was performed
For each patient, the arithmetic mean of the two FTY720 trough blood levels from month 3 and 6 was calculated. This was taken as the patient's steady-state trough levels. Venous blood samples (3 mL) were collected before the dose in ethylenediaminetetraacetic acid (EDTA)-containing tubes at protocol-scheduled visits at months 3 and 6 in all patients.
Outcome measures
| Measure |
Placebo
n=68 Participants
Core study: patients received placebo, once daily for 6 months. Extension: In dose-blind period patients were re-randomized into either fingolimod 1.25 mg or 5.0 mg once per day for 6-15 months. In open-label period patients received fingolimod 1.25 mg once per day for 15 to 24 months. Later, all patients converted to fingolimod 0.5 mg, once daily for rest of the study participation.
|
Fingolimod (FTY720) 1.25 mg/Day
n=56 Participants
Core study: patients received fingolimod 1.25 mg, once daily for 6 months. Extension: In dose -blind period and open label, fingolimod 1.25 mg once daily for 9-18 months (6 months to 24 months). Later, all patients converted to fingolimod 0.5 mg, once daily for rest of the study participation.
|
Fingolimod (FTY720) 5.0 mg/Day
Core study: patients received fingolimod 5.0 mg, once daily for 6 months. Extension: In dose-blind period fingolimod 5.0 mg once daily for 6-15 months. For open-label phase 1.25mg once daily for 15 to 24 months. Later, all patients converted to fingolimod 0.5 mg, once daily for rest of the study participation.
|
|---|---|---|---|
|
Mean Trough Blood Concentrations of FTY720
Month 3 (core)
|
7.64 ng/mL
Standard Deviation 5.44
|
30.5 ng/mL
Standard Deviation 18.8
|
—
|
|
Mean Trough Blood Concentrations of FTY720
Month 6 (core)
|
7.38 ng/mL
Standard Deviation 4.57
|
28.9 ng/mL
Standard Deviation 22.1
|
—
|
Adverse Events
Placebo
Serious events: 25 serious events
Other events: 86 other events
Deaths: 0 deaths
Fingolimod (FTY720) 1.25 mg
Serious events: 19 serious events
Other events: 88 other events
Deaths: 0 deaths
Fingolimod (FTY720) 5.0 mg
Serious events: 32 serious events
Other events: 92 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Placebo
n=93 participants at risk
Core study: patients received placebo, once daily for 6 months. Extension: In dose-blind period patients were re-randomized into either fingolimod 1.25 mg or 5.0 mg once per day for 6-15 months. In open-label period patients received fingolimod 1.25 mg once per day for 15 to 24 months. Later, all patients converted to fingolimod 0.5 mg, once daily for rest of the study participation.
|
Fingolimod (FTY720) 1.25 mg
n=94 participants at risk
Core study: patients received fingolimod 1.25 mg, once daily for 6 months. Extension: In dose -blind period and open label, fingolimod 1.25 mg once daily for 9-18 months (6 months to 24 months). Later, all patients converted to fingolimod 0.5 mg, once daily for rest of the study participation.
|
Fingolimod (FTY720) 5.0 mg
n=94 participants at risk
Core study: patients received fingolimod 5.0 mg, once daily for 6 months. Extension: In dose-blind period fingolimod 5.0 mg once daily for 6-15 months. For open-label phase 1.25mg once daily for 15 to 24 months. Later, all patients converted to fingolimod 0.5 mg, once daily for rest of the study participation.
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Neutropenia
|
0.00%
0/93
|
0.00%
0/94
|
1.1%
1/94
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
1.1%
1/93
|
0.00%
0/94
|
0.00%
0/94
|
|
Cardiac disorders
Atrioventricular block first degree
|
0.00%
0/93
|
1.1%
1/94
|
0.00%
0/94
|
|
Cardiac disorders
Bradycardia
|
1.1%
1/93
|
0.00%
0/94
|
3.2%
3/94
|
|
Cardiac disorders
Coronary artery thrombosis
|
1.1%
1/93
|
0.00%
0/94
|
0.00%
0/94
|
|
Cardiac disorders
Extrasystoles
|
1.1%
1/93
|
0.00%
0/94
|
1.1%
1/94
|
|
Cardiac disorders
Hypertensive heart disease
|
0.00%
0/93
|
1.1%
1/94
|
0.00%
0/94
|
|
Cardiac disorders
Myocardial ischaemia
|
1.1%
1/93
|
0.00%
0/94
|
0.00%
0/94
|
|
Cardiac disorders
Palpitations
|
1.1%
1/93
|
0.00%
0/94
|
1.1%
1/94
|
|
Cardiac disorders
Ventricular extrasystoles
|
0.00%
0/93
|
0.00%
0/94
|
1.1%
1/94
|
|
Endocrine disorders
Adrenal mass
|
0.00%
0/93
|
0.00%
0/94
|
1.1%
1/94
|
|
Eye disorders
Eye oedema
|
1.1%
1/93
|
0.00%
0/94
|
0.00%
0/94
|
|
Eye disorders
Macular oedema
|
0.00%
0/93
|
2.1%
2/94
|
2.1%
2/94
|
|
Eye disorders
Retinal detachment
|
1.1%
1/93
|
0.00%
0/94
|
0.00%
0/94
|
|
Eye disorders
Retinal vein thrombosis
|
0.00%
0/93
|
0.00%
0/94
|
1.1%
1/94
|
|
Eye disorders
Vision blurred
|
0.00%
0/93
|
0.00%
0/94
|
1.1%
1/94
|
|
Gastrointestinal disorders
Abdominal pain
|
1.1%
1/93
|
0.00%
0/94
|
0.00%
0/94
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.00%
0/93
|
1.1%
1/94
|
0.00%
0/94
|
|
Gastrointestinal disorders
Anogenital dysplasia
|
0.00%
0/93
|
1.1%
1/94
|
0.00%
0/94
|
|
Gastrointestinal disorders
Colonic pseudo-obstruction
|
1.1%
1/93
|
0.00%
0/94
|
0.00%
0/94
|
|
Gastrointestinal disorders
Enterocolitis
|
1.1%
1/93
|
0.00%
0/94
|
0.00%
0/94
|
|
Gastrointestinal disorders
Inguinal hernia
|
0.00%
0/93
|
0.00%
0/94
|
1.1%
1/94
|
|
Gastrointestinal disorders
Intestinal polyp
|
1.1%
1/93
|
0.00%
0/94
|
0.00%
0/94
|
|
Gastrointestinal disorders
Nausea
|
1.1%
1/93
|
0.00%
0/94
|
0.00%
0/94
|
|
Gastrointestinal disorders
Volvulus
|
0.00%
0/93
|
0.00%
0/94
|
1.1%
1/94
|
|
General disorders
Chest pain
|
0.00%
0/93
|
1.1%
1/94
|
2.1%
2/94
|
|
General disorders
Concomitant disease progression
|
0.00%
0/93
|
0.00%
0/94
|
1.1%
1/94
|
|
General disorders
Oedema peripheral
|
0.00%
0/93
|
1.1%
1/94
|
0.00%
0/94
|
|
Hepatobiliary disorders
Cholelithiasis
|
0.00%
0/93
|
2.1%
2/94
|
0.00%
0/94
|
|
Hepatobiliary disorders
Hepatitis
|
0.00%
0/93
|
1.1%
1/94
|
0.00%
0/94
|
|
Hepatobiliary disorders
Jaundice
|
0.00%
0/93
|
1.1%
1/94
|
0.00%
0/94
|
|
Infections and infestations
Appendicitis
|
0.00%
0/93
|
0.00%
0/94
|
1.1%
1/94
|
|
Infections and infestations
Dengue fever
|
1.1%
1/93
|
0.00%
0/94
|
0.00%
0/94
|
|
Infections and infestations
Herpes zoster
|
1.1%
1/93
|
0.00%
0/94
|
0.00%
0/94
|
|
Infections and infestations
Otitis externa
|
1.1%
1/93
|
0.00%
0/94
|
0.00%
0/94
|
|
Infections and infestations
Pyelonephritis acute
|
1.1%
1/93
|
0.00%
0/94
|
0.00%
0/94
|
|
Infections and infestations
Salpingitis
|
0.00%
0/93
|
0.00%
0/94
|
1.1%
1/94
|
|
Infections and infestations
Skin infection
|
1.1%
1/93
|
0.00%
0/94
|
0.00%
0/94
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/93
|
0.00%
0/94
|
1.1%
1/94
|
|
Injury, poisoning and procedural complications
Clavicle fracture
|
0.00%
0/93
|
0.00%
0/94
|
1.1%
1/94
|
|
Injury, poisoning and procedural complications
Drug exposure during pregnancy
|
0.00%
0/93
|
0.00%
0/94
|
1.1%
1/94
|
|
Injury, poisoning and procedural complications
Fibula fracture
|
1.1%
1/93
|
0.00%
0/94
|
0.00%
0/94
|
|
Injury, poisoning and procedural complications
Hip fracture
|
1.1%
1/93
|
0.00%
0/94
|
0.00%
0/94
|
|
Injury, poisoning and procedural complications
Injury
|
1.1%
1/93
|
0.00%
0/94
|
0.00%
0/94
|
|
Injury, poisoning and procedural complications
Joint dislocation
|
1.1%
1/93
|
0.00%
0/94
|
0.00%
0/94
|
|
Injury, poisoning and procedural complications
Limb injury
|
1.1%
1/93
|
0.00%
0/94
|
1.1%
1/94
|
|
Injury, poisoning and procedural complications
Lower limb fracture
|
0.00%
0/93
|
0.00%
0/94
|
1.1%
1/94
|
|
Injury, poisoning and procedural complications
Procedural pain
|
1.1%
1/93
|
0.00%
0/94
|
0.00%
0/94
|
|
Injury, poisoning and procedural complications
Radius fracture
|
0.00%
0/93
|
0.00%
0/94
|
1.1%
1/94
|
|
Injury, poisoning and procedural complications
Road traffic accident
|
1.1%
1/93
|
1.1%
1/94
|
0.00%
0/94
|
|
Injury, poisoning and procedural complications
Tibia fracture
|
1.1%
1/93
|
0.00%
0/94
|
0.00%
0/94
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/93
|
1.1%
1/94
|
0.00%
0/94
|
|
Investigations
Chest X-ray abnormal
|
0.00%
0/93
|
1.1%
1/94
|
0.00%
0/94
|
|
Investigations
Heart rate abnormal
|
1.1%
1/93
|
0.00%
0/94
|
0.00%
0/94
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion
|
0.00%
0/93
|
1.1%
1/94
|
0.00%
0/94
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
0.00%
0/93
|
1.1%
1/94
|
0.00%
0/94
|
|
Musculoskeletal and connective tissue disorders
Spinal column stenosis
|
0.00%
0/93
|
1.1%
1/94
|
0.00%
0/94
|
|
Musculoskeletal and connective tissue disorders
Spondylolisthesis
|
0.00%
0/93
|
0.00%
0/94
|
1.1%
1/94
|
|
Musculoskeletal and connective tissue disorders
Synovial cyst
|
1.1%
1/93
|
0.00%
0/94
|
0.00%
0/94
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma
|
1.1%
1/93
|
0.00%
0/94
|
2.1%
2/94
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Benign breast neoplasm
|
1.1%
1/93
|
0.00%
0/94
|
0.00%
0/94
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Benign lung neoplasm
|
0.00%
0/93
|
0.00%
0/94
|
1.1%
1/94
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bowen's disease
|
1.1%
1/93
|
0.00%
0/94
|
0.00%
0/94
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer
|
1.1%
1/93
|
0.00%
0/94
|
0.00%
0/94
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cervix carcinoma
|
0.00%
0/93
|
0.00%
0/94
|
1.1%
1/94
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lentigo maligna stage unspecified
|
0.00%
0/93
|
1.1%
1/94
|
0.00%
0/94
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant melanoma
|
1.1%
1/93
|
2.1%
2/94
|
0.00%
0/94
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma
|
0.00%
0/93
|
1.1%
1/94
|
3.2%
3/94
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Thyroid cancer
|
0.00%
0/93
|
0.00%
0/94
|
1.1%
1/94
|
|
Nervous system disorders
Convulsion
|
1.1%
1/93
|
0.00%
0/94
|
0.00%
0/94
|
|
Nervous system disorders
Dizziness
|
0.00%
0/93
|
0.00%
0/94
|
1.1%
1/94
|
|
Nervous system disorders
Epilepsy
|
0.00%
0/93
|
0.00%
0/94
|
1.1%
1/94
|
|
Nervous system disorders
Multiple sclerosis relapse
|
1.1%
1/93
|
1.1%
1/94
|
0.00%
0/94
|
|
Nervous system disorders
Paraparesis
|
0.00%
0/93
|
1.1%
1/94
|
0.00%
0/94
|
|
Nervous system disorders
Reversible posterior leukoencephalopathy syndrome
|
0.00%
0/93
|
0.00%
0/94
|
1.1%
1/94
|
|
Nervous system disorders
Status epilepticus
|
1.1%
1/93
|
0.00%
0/94
|
0.00%
0/94
|
|
Nervous system disorders
Syncope
|
0.00%
0/93
|
0.00%
0/94
|
1.1%
1/94
|
|
Pregnancy, puerperium and perinatal conditions
Abortion
|
0.00%
0/93
|
0.00%
0/94
|
1.1%
1/94
|
|
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous
|
0.00%
0/93
|
0.00%
0/94
|
1.1%
1/94
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/93
|
2.1%
2/94
|
0.00%
0/94
|
|
Psychiatric disorders
Bipolar I disorder
|
1.1%
1/93
|
0.00%
0/94
|
0.00%
0/94
|
|
Psychiatric disorders
Suicide attempt
|
1.1%
1/93
|
0.00%
0/94
|
0.00%
0/94
|
|
Renal and urinary disorders
Calculus ureteric
|
0.00%
0/93
|
0.00%
0/94
|
1.1%
1/94
|
|
Renal and urinary disorders
Hypertonic bladder
|
1.1%
1/93
|
0.00%
0/94
|
0.00%
0/94
|
|
Renal and urinary disorders
Nephrolithiasis
|
0.00%
0/93
|
0.00%
0/94
|
1.1%
1/94
|
|
Renal and urinary disorders
Ureteric obstruction
|
0.00%
0/93
|
0.00%
0/94
|
1.1%
1/94
|
|
Renal and urinary disorders
Urethral stenosis
|
0.00%
0/93
|
0.00%
0/94
|
1.1%
1/94
|
|
Reproductive system and breast disorders
Endometriosis
|
0.00%
0/93
|
0.00%
0/94
|
1.1%
1/94
|
|
Reproductive system and breast disorders
Ovarian cyst
|
0.00%
0/93
|
0.00%
0/94
|
1.1%
1/94
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
0.00%
0/93
|
0.00%
0/94
|
2.1%
2/94
|
|
Respiratory, thoracic and mediastinal disorders
Bronchospasm
|
1.1%
1/93
|
0.00%
0/94
|
0.00%
0/94
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/93
|
0.00%
0/94
|
1.1%
1/94
|
|
Skin and subcutaneous tissue disorders
Hirsutism
|
0.00%
0/93
|
1.1%
1/94
|
0.00%
0/94
|
|
Skin and subcutaneous tissue disorders
Rosacea
|
0.00%
0/93
|
1.1%
1/94
|
0.00%
0/94
|
|
Skin and subcutaneous tissue disorders
Skin nodule
|
0.00%
0/93
|
0.00%
0/94
|
1.1%
1/94
|
|
Skin and subcutaneous tissue disorders
Skin ulcer
|
0.00%
0/93
|
0.00%
0/94
|
1.1%
1/94
|
|
Vascular disorders
Deep vein thrombosis
|
0.00%
0/93
|
1.1%
1/94
|
0.00%
0/94
|
|
Vascular disorders
Hypertension
|
0.00%
0/93
|
0.00%
0/94
|
1.1%
1/94
|
|
Vascular disorders
Varicose ulceration
|
1.1%
1/93
|
0.00%
0/94
|
0.00%
0/94
|
|
Vascular disorders
Varicose vein
|
0.00%
0/93
|
0.00%
0/94
|
1.1%
1/94
|
Other adverse events
| Measure |
Placebo
n=93 participants at risk
Core study: patients received placebo, once daily for 6 months. Extension: In dose-blind period patients were re-randomized into either fingolimod 1.25 mg or 5.0 mg once per day for 6-15 months. In open-label period patients received fingolimod 1.25 mg once per day for 15 to 24 months. Later, all patients converted to fingolimod 0.5 mg, once daily for rest of the study participation.
|
Fingolimod (FTY720) 1.25 mg
n=94 participants at risk
Core study: patients received fingolimod 1.25 mg, once daily for 6 months. Extension: In dose -blind period and open label, fingolimod 1.25 mg once daily for 9-18 months (6 months to 24 months). Later, all patients converted to fingolimod 0.5 mg, once daily for rest of the study participation.
|
Fingolimod (FTY720) 5.0 mg
n=94 participants at risk
Core study: patients received fingolimod 5.0 mg, once daily for 6 months. Extension: In dose-blind period fingolimod 5.0 mg once daily for 6-15 months. For open-label phase 1.25mg once daily for 15 to 24 months. Later, all patients converted to fingolimod 0.5 mg, once daily for rest of the study participation.
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Leukopenia
|
7.5%
7/93
|
14.9%
14/94
|
16.0%
15/94
|
|
Blood and lymphatic system disorders
Lymphopenia
|
14.0%
13/93
|
19.1%
18/94
|
19.1%
18/94
|
|
Cardiac disorders
Palpitations
|
5.4%
5/93
|
1.1%
1/94
|
3.2%
3/94
|
|
Eye disorders
Conjunctivitis
|
2.2%
2/93
|
7.4%
7/94
|
3.2%
3/94
|
|
Gastrointestinal disorders
Abdominal pain
|
6.5%
6/93
|
5.3%
5/94
|
7.4%
7/94
|
|
Gastrointestinal disorders
Abdominal pain upper
|
6.5%
6/93
|
10.6%
10/94
|
8.5%
8/94
|
|
Gastrointestinal disorders
Aphthous stomatitis
|
4.3%
4/93
|
5.3%
5/94
|
4.3%
4/94
|
|
Gastrointestinal disorders
Constipation
|
12.9%
12/93
|
4.3%
4/94
|
12.8%
12/94
|
|
Gastrointestinal disorders
Diarrhoea
|
12.9%
12/93
|
19.1%
18/94
|
16.0%
15/94
|
|
Gastrointestinal disorders
Dyspepsia
|
4.3%
4/93
|
10.6%
10/94
|
4.3%
4/94
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
5.4%
5/93
|
1.1%
1/94
|
1.1%
1/94
|
|
Gastrointestinal disorders
Nausea
|
8.6%
8/93
|
10.6%
10/94
|
17.0%
16/94
|
|
Gastrointestinal disorders
Toothache
|
2.2%
2/93
|
5.3%
5/94
|
8.5%
8/94
|
|
Gastrointestinal disorders
Vomiting
|
5.4%
5/93
|
6.4%
6/94
|
6.4%
6/94
|
|
General disorders
Asthenia
|
8.6%
8/93
|
4.3%
4/94
|
3.2%
3/94
|
|
General disorders
Chest pain
|
2.2%
2/93
|
4.3%
4/94
|
5.3%
5/94
|
|
General disorders
Fatigue
|
23.7%
22/93
|
24.5%
23/94
|
17.0%
16/94
|
|
General disorders
Gait disturbance
|
2.2%
2/93
|
5.3%
5/94
|
2.1%
2/94
|
|
General disorders
Oedema peripheral
|
5.4%
5/93
|
5.3%
5/94
|
5.3%
5/94
|
|
General disorders
Pyrexia
|
6.5%
6/93
|
6.4%
6/94
|
12.8%
12/94
|
|
Infections and infestations
Bronchitis
|
9.7%
9/93
|
18.1%
17/94
|
12.8%
12/94
|
|
Infections and infestations
Cystitis
|
4.3%
4/93
|
2.1%
2/94
|
6.4%
6/94
|
|
Infections and infestations
Ear infection
|
1.1%
1/93
|
6.4%
6/94
|
3.2%
3/94
|
|
Infections and infestations
Gastroenteritis
|
4.3%
4/93
|
8.5%
8/94
|
14.9%
14/94
|
|
Infections and infestations
Herpes zoster
|
4.3%
4/93
|
7.4%
7/94
|
4.3%
4/94
|
|
Infections and infestations
Influenza
|
17.2%
16/93
|
24.5%
23/94
|
23.4%
22/94
|
|
Infections and infestations
Nasopharyngitis
|
36.6%
34/93
|
41.5%
39/94
|
44.7%
42/94
|
|
Infections and infestations
Oral herpes
|
5.4%
5/93
|
5.3%
5/94
|
4.3%
4/94
|
|
Infections and infestations
Pharyngitis
|
7.5%
7/93
|
11.7%
11/94
|
5.3%
5/94
|
|
Infections and infestations
Respiratory tract infection
|
2.2%
2/93
|
5.3%
5/94
|
3.2%
3/94
|
|
Infections and infestations
Rhinitis
|
6.5%
6/93
|
5.3%
5/94
|
2.1%
2/94
|
|
Infections and infestations
Sinusitis
|
10.8%
10/93
|
12.8%
12/94
|
12.8%
12/94
|
|
Infections and infestations
Tooth abscess
|
1.1%
1/93
|
6.4%
6/94
|
3.2%
3/94
|
|
Infections and infestations
Tooth infection
|
2.2%
2/93
|
7.4%
7/94
|
7.4%
7/94
|
|
Infections and infestations
Upper respiratory tract infection
|
20.4%
19/93
|
20.2%
19/94
|
19.1%
18/94
|
|
Infections and infestations
Urinary tract infection
|
11.8%
11/93
|
10.6%
10/94
|
11.7%
11/94
|
|
Infections and infestations
Viral upper respiratory tract infection
|
5.4%
5/93
|
6.4%
6/94
|
4.3%
4/94
|
|
Injury, poisoning and procedural complications
Contusion
|
6.5%
6/93
|
5.3%
5/94
|
4.3%
4/94
|
|
Injury, poisoning and procedural complications
Fall
|
7.5%
7/93
|
6.4%
6/94
|
4.3%
4/94
|
|
Injury, poisoning and procedural complications
Joint sprain
|
4.3%
4/93
|
5.3%
5/94
|
2.1%
2/94
|
|
Investigations
Alanine aminotransferase increased
|
19.4%
18/93
|
12.8%
12/94
|
16.0%
15/94
|
|
Investigations
Aspartate aminotransferase increased
|
5.4%
5/93
|
3.2%
3/94
|
2.1%
2/94
|
|
Investigations
Lymphocyte count decreased
|
3.2%
3/93
|
6.4%
6/94
|
7.4%
7/94
|
|
Investigations
White blood cell count decreased
|
4.3%
4/93
|
5.3%
5/94
|
5.3%
5/94
|
|
Metabolism and nutrition disorders
Decreased appetite
|
2.2%
2/93
|
4.3%
4/94
|
5.3%
5/94
|
|
Metabolism and nutrition disorders
Hypercholesterolaemia
|
6.5%
6/93
|
6.4%
6/94
|
5.3%
5/94
|
|
Metabolism and nutrition disorders
Hypertriglyceridaemia
|
5.4%
5/93
|
2.1%
2/94
|
4.3%
4/94
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
18.3%
17/93
|
14.9%
14/94
|
12.8%
12/94
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
23.7%
22/93
|
17.0%
16/94
|
20.2%
19/94
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
6.5%
6/93
|
4.3%
4/94
|
8.5%
8/94
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
5.4%
5/93
|
3.2%
3/94
|
5.3%
5/94
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
5.4%
5/93
|
6.4%
6/94
|
6.4%
6/94
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
4.3%
4/93
|
3.2%
3/94
|
5.3%
5/94
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
3.2%
3/93
|
8.5%
8/94
|
4.3%
4/94
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
19.4%
18/93
|
16.0%
15/94
|
16.0%
15/94
|
|
Musculoskeletal and connective tissue disorders
Tendonitis
|
7.5%
7/93
|
1.1%
1/94
|
1.1%
1/94
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Melanocytic naevus
|
5.4%
5/93
|
5.3%
5/94
|
5.3%
5/94
|
|
Nervous system disorders
Dizziness
|
14.0%
13/93
|
8.5%
8/94
|
10.6%
10/94
|
|
Nervous system disorders
Headache
|
30.1%
28/93
|
37.2%
35/94
|
26.6%
25/94
|
|
Nervous system disorders
Hypoaesthesia
|
14.0%
13/93
|
8.5%
8/94
|
9.6%
9/94
|
|
Nervous system disorders
Migraine
|
10.8%
10/93
|
6.4%
6/94
|
6.4%
6/94
|
|
Nervous system disorders
Muscle spasticity
|
1.1%
1/93
|
2.1%
2/94
|
6.4%
6/94
|
|
Nervous system disorders
Paraesthesia
|
9.7%
9/93
|
10.6%
10/94
|
5.3%
5/94
|
|
Nervous system disorders
Somnolence
|
1.1%
1/93
|
4.3%
4/94
|
6.4%
6/94
|
|
Nervous system disorders
Tremor
|
3.2%
3/93
|
5.3%
5/94
|
2.1%
2/94
|
|
Psychiatric disorders
Anxiety
|
4.3%
4/93
|
7.4%
7/94
|
7.4%
7/94
|
|
Psychiatric disorders
Depression
|
16.1%
15/93
|
12.8%
12/94
|
14.9%
14/94
|
|
Psychiatric disorders
Insomnia
|
12.9%
12/93
|
16.0%
15/94
|
8.5%
8/94
|
|
Renal and urinary disorders
Pollakiuria
|
5.4%
5/93
|
3.2%
3/94
|
1.1%
1/94
|
|
Renal and urinary disorders
Urinary incontinence
|
1.1%
1/93
|
9.6%
9/94
|
1.1%
1/94
|
|
Reproductive system and breast disorders
Dysmenorrhoea
|
3.2%
3/93
|
5.3%
5/94
|
4.3%
4/94
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
4.3%
4/93
|
1.1%
1/94
|
6.4%
6/94
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
12.9%
12/93
|
17.0%
16/94
|
20.2%
19/94
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
5.4%
5/93
|
7.4%
7/94
|
16.0%
15/94
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
10.8%
10/93
|
6.4%
6/94
|
9.6%
9/94
|
|
Skin and subcutaneous tissue disorders
Acne
|
3.2%
3/93
|
3.2%
3/94
|
6.4%
6/94
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
6.5%
6/93
|
7.4%
7/94
|
6.4%
6/94
|
|
Skin and subcutaneous tissue disorders
Eczema
|
3.2%
3/93
|
6.4%
6/94
|
6.4%
6/94
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
5.4%
5/93
|
4.3%
4/94
|
4.3%
4/94
|
|
Skin and subcutaneous tissue disorders
Rash
|
7.5%
7/93
|
6.4%
6/94
|
8.5%
8/94
|
|
Skin and subcutaneous tissue disorders
Skin lesion
|
5.4%
5/93
|
0.00%
0/94
|
1.1%
1/94
|
|
Vascular disorders
Hypertension
|
14.0%
13/93
|
20.2%
19/94
|
10.6%
10/94
|
Additional Information
Study director
Novartis pharmaceuticals
Phone: 862-778-8300
Results disclosure agreements
- Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
- Publication restrictions are in place
Restriction type: OTHER