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Trial record 1 of 1 for:    NCT00355134
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Efficacy and Safety of Fingolimod (FTY720) in Patients With Relapsing-remitting Multiple Sclerosis (FREEDOMS II)

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ClinicalTrials.gov Identifier: NCT00355134
Recruitment Status : Completed
First Posted : July 21, 2006
Results First Posted : June 26, 2012
Last Update Posted : August 7, 2012
Sponsor:
Information provided by (Responsible Party):
Novartis

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Multiple Sclerosis
Interventions Drug: Fingolimod
Drug: Placebo
Enrollment 1083
Recruitment Details  
Pre-assignment Details Patients were randomized to receive fingolimod 0.5 mg, 1.25 mg or placebo for up to 24 months. Upon entry into the Extension phase, patients treated with fingolimod 0.5 mg or 1.25 mg during the Core phase continued treatment at the same dose, those previously treated with placebo were re-randomized in to receive one of the two doses of fingolimod.
Arm/Group Title Fingolimod 1.25 mg Fingolimod 0.5 mg Placebo (Core) Extension: Fingolimod 1.25 mg Extension: Fingolimod 0.5 mg
Hide Arm/Group Description Participants received 1.25 mg fingolimod orally once a day for up to 24 months during the core phase. In the Extension phase participants continued to receive 1.25 mg fingolimod orally. Upon implementation of a protocol amendment, all patients taking 1.25 mg fingolimod were switched to 0.5 mg fingolimod orally once a day. Participants received 0.5 mg fingolimod orally once a day for up to 24 months during the core phase. In the Extension phase participants continued to receive 0.5 mg fingolimod orally once a day. Participants received placebo capsules orally once a day for up to 24 months during the core phase. Upon implementation of a protocol amendment, all patients taking placebo were switched to 0.5 mg fingolimod orally once a day. Participants who had received placebo in the Core phase and then received 1.25 mg fingolimod orally once a day in the Extension phase. Upon implementation of a protocol amendment, all patients taking 1.25 mg fingolimod were switched to 0.5 mg fingolimod orally once a day. Participants who had received placebo in the Core phase and then received 0.5 mg fingolimod orally once a day in the Extension phase.
Period Title: Core Phase
Started 370 358 355 0 0
Completed 251 272 255 0 0
Not Completed 119 86 100 0 0
Reason Not Completed
Withdrawal by Subject             35             24             35             0             0
Adverse Event             28             22             16             0             0
Lost to Follow-up             17             13             21             0             0
Abnormal laboratory value(s)             19             14             2             0             0
Unsatisfactory therapeutic effect             10             6             17             0             0
Administrative problems             5             3             5             0             0
Protocol Violation             3             2             2             0             0
Abnormal test procedure result(s)             1             2             1             0             0
Condition no longer requires study drug             1             0             1             0             0
Period Title: Extension Phase
Started 203 217 0 105 107
Completed 172 180 0 89 88
Not Completed 31 37 0 16 19
Reason Not Completed
Withdrawal by Subject             7             11             0             7             5
Adverse Event             13             9             0             3             5
Lost to Follow-up             2             6             0             2             4
Abnormal laboratory value(s)             4             2             0             2             2
Administrative problems             2             4             0             1             1
Unsatisfactory therapeutic effect             3             4             0             0             1
Abnormal test procedure result(s)             0             1             0             0             1
Protocol Violation             0             0             0             1             0
Arm/Group Title Fingolimod 1.25 mg Fingolimod 0.5 mg Placebo (Core) Extension: Fingolimod 1.25 mg Extension: Fingolimod 0.5 mg Total
Hide Arm/Group Description Participants received 1.25 mg fingolimod orally once a day for up to 24 months during the core phase. In the Extension phase participants continued to receive 1.25 mg fingolimod orally. Upon implementation of a protocol amendment, all patients taking 1.25 mg fingolimod were switched to 0.5 mg fingolimod orally once a day. Participants received 0.5 mg fingolimod orally once a day for up to 24 months during the core phase. In the Extension phase participants continued to receive 0.5 mg fingolimod orally once a day. Participants received placebo capsules orally once a day for up to 24 months during the core phase. Upon implementation of a protocol amendment, all patients taking placebo were switched to 0.5 mg fingolimod orally once a day. Participants who had received placebo in the Core phase and then received 1.25 mg fingolimod orally once a day in the Extension phase. Upon implementation of a protocol amendment, all patients taking 1.25 mg fingolimod were switched to 0.5 mg fingolimod orally once a day. Participants who had received placebo in the Core phase and then received 0.5 mg fingolimod orally once a day in the Extension phase. Total of all reporting groups
Overall Number of Baseline Participants 370 358 355 105 107 1295
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 370 participants 358 participants 355 participants 105 participants 107 participants 1295 participants
40.9  (8.90) 40.6  (8.39) 40.1  (8.42) NA [2]   (NA) NA [2]   (NA) 40.5  (8.58)
[1]
Measure Description: Demographic data for the Core phase participant population.
[2]
Age demographic data presented for Core phase population only.
Age Continuous   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 370 participants 358 participants 355 participants 105 participants 107 participants 1295 participants
40.6  (8.71) 40.8  (7.96) NA [2]   (NA) 39.8  (8.32) 41.1  (8.11) 40.6  (8.28)
[1]
Measure Description: Demographic data for the Extension phase population. The number of participants in each treatment group in the Extension phase was 203, 217, 0, 105 and 107; Total participants 632.
[2]
Age demographic data presented for the Extension phase population only.
Gender   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 370 participants 358 participants 355 participants 105 participants 107 participants 1295 participants
Female 281 275 288 0 0 844
Male 89 83 67 0 0 239
[1]
Measure Description: Demographic data for the Core phase participant population.
Gender   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 370 participants 358 participants 355 participants 105 participants 107 participants 1295 participants
Female 148 160 0 88 85 481
Male 55 57 0 17 22 151
[1]
Measure Description: Demographic data for the Extension phase population. The number of participants in each treatment group in the Extension phase was 203, 217, 0, 105 and 107; Total participants 632.
1.Primary Outcome
Title Aggregate Annualized Relapse Rate (ARR) Estimate up to Month 24
Hide Description

ARR is the average number of relapses in a year calculated by negative binomial regression as the sum of confirmed relapses of all patients in the group divided by the sum of the number of days on study of all patients in the group and multiplied by 365.25.

A relapse was defined as the appearance of a new neurological abnormality or worsening of previously stable or improving pre-existing neurological abnormality, separated by at least 30 days from onset of a preceding clinical demyelinating event. The abnormality must be present for at least 24 hours and occur in the absence of fever (<37.5C) or known infection. A relapse must be confirmed by the Independent Evaluating Physician (examining neurologist).

ARR estimates were calculated from a negative binomial regression model adjusted for treatment, pooled center, number of relapses in the previous 2 years prior to enrollment, and Baseline expanded disability status scale (EDSS).

Time Frame 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set, including all patients who were randomized and took at least one dose of study drug.
Arm/Group Title Fingolimod 1.25 mg Fingolimod 0.5 mg Placebo
Hide Arm/Group Description:
Participants received 1.25 mg fingolimod orally once a day for up to 24 months during the core phase. In the Extension phase participants continued to receive 1.25 mg fingolimod orally. Upon implementation of a protocol amendment, all patients taking 1.25 mg fingolimod were switched to 0.5 mg fingolimod orally once a day.
Participants received 0.5 mg fingolimod orally once a day for up to 24 months during the core phase. In the Extension phase participants continued to receive 0.5 mg fingolimod orally once a day.
Participants received placebo capsules orally once a day for up to 24 months during the core phase. In the Extension phase participants received either 1.25 or 0.5 mg fingolimod orally once a day. Upon implementation of a protocol amendment, all patients taking 1.25 mg fingolimod were switched to 0.5 mg fingolimod orally once a day. Upon implementation of a protocol amendment, all patients taking placebo were switched to 0.5 mg fingolimod orally once a day.
Overall Number of Participants Analyzed 370 358 355
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: relapses per year
0.203
(0.165 to 0.249)
0.208
(0.170 to 0.254)
0.403
(0.342 to 0.475)
2.Secondary Outcome
Title Aggregate Annualized Relapse Rate (ARR) Estimate up to End of Study
Hide Description

ARR is the average number of relapses in a year calculated by negative binomial regression as the sum of confirmed relapses of all patients in the group divided by the sum of the number of days on study of all patients in the group and multiplied by 365.25.

A relapse was defined as the appearance of a new neurological abnormality or worsening of previously stable or improving pre-existing neurological abnormality, separated by at least 30 days from onset of a preceding clinical demyelinating event. The abnormality must be present for at least 24 hours and occur in the absence of fever (<37.5C) or known infection. A relapse must be confirmed by the Independent Evaluating Physician (examining neurologist).

ARR estimates were calculated from a negative binomial regression model adjusted for treatment, pooled center, number of relapses in the previous 2 years prior to enrollment, and Baseline expanded disability status scale (EDSS).

Time Frame From Baseline until end of study (up to approximately 54 months).
Hide Outcome Measure Data
Hide Analysis Population Description
Core intent-to-treat (ITT) population: All patients who were randomized in the Core phase and received at least one dose of Core phase drug.
Arm/Group Title Fingolimod 1.25 mg Fingolimod 0.5 mg Placebo
Hide Arm/Group Description:
Participants received 1.25 mg fingolimod orally once a day for up to 24 months during the core phase. In the Extension phase participants continued to receive 1.25 mg fingolimod orally. Upon implementation of a protocol amendment, all patients taking 1.25 mg fingolimod were switched to 0.5 mg fingolimod orally once a day.
Participants received 0.5 mg fingolimod orally once a day for up to 24 months during the core phase. In the Extension phase participants continued to receive 0.5 mg fingolimod orally once a day.
Participants received placebo capsules orally once a day for up to 24 months during the core phase. In the Extension phase participants received either 1.25 or 0.5 mg fingolimod orally once a day. Upon implementation of a protocol amendment, all patients taking 1.25 mg fingolimod were switched to 0.5 mg fingolimod orally once a day. Upon implementation of a protocol amendment, all patients taking placebo were switched to 0.5 mg fingolimod orally once a day.
Overall Number of Participants Analyzed 370 358 355
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: relapses per year
0.180
(0.147 to 0.222)
0.192
(0.157 to 0.234)
0.363
(0.305 to 0.431)
3.Secondary Outcome
Title Percent Change From Baseline in Brain Volume
Hide Description Brain volume was measured using magnetic resonance imaging (MRI). Change from Baseline in brain volume is expressed as a percentage of the Baseline brain volume.
Time Frame Baseline, Month 24 and end of study (up to approximately 54 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Core intent-to-treat (ITT) population: All patients who were randomized in the Core phase and received at least one dose of Core phase drug. Patients were grouped according to the assigned treatment. "N" indicates the number of participants with data available for the specified time period.
Arm/Group Title Fingolimod 1.25 mg Fingolimod 0.5 mg Placebo
Hide Arm/Group Description:
Participants received 1.25 mg fingolimod orally once a day for up to 24 months during the core phase. In the Extension phase participants continued to receive 1.25 mg fingolimod orally. Upon implementation of a protocol amendment, all patients taking 1.25 mg fingolimod were switched to 0.5 mg fingolimod orally once a day.
Participants received 0.5 mg fingolimod orally once a day for up to 24 months during the core phase. In the Extension phase participants continued to receive 0.5 mg fingolimod orally once a day.
Participants received placebo capsules orally once a day for up to 24 months during the core phase. In the Extension phase participants received either 1.25 or 0.5 mg fingolimod orally once a day. Upon implementation of a protocol amendment, all patients taking 1.25 mg fingolimod were switched to 0.5 mg fingolimod orally once a day. Upon implementation of a protocol amendment, all patients taking placebo were switched to 0.5 mg fingolimod orally once a day.
Overall Number of Participants Analyzed 370 358 355
Mean (Standard Deviation)
Unit of Measure: percent change
Month 24 [N=247; 266; 249] -0.595  (1.3897) -0.858  (1.2215) -1.279  (1.5028)
End of study [N=178; 187; 182] -1.130  (1.6380) -1.266  (1.6941) -1.694  (1.9567)
4.Secondary Outcome
Title Number of New or Newly Enlarged T2 Lesions
Hide Description Inflammatory disease activity was assessed by magnetic resonance imaging (MRI) measurement of the number of new or newly enlarged T2 lesions, by year.
Time Frame From Baseline until Month 48
Hide Outcome Measure Data
Hide Analysis Population Description
Core intent-to-treat (ITT) population: All patients who were randomized in the Core phase and received at least one dose of Core phase drug. Patients were grouped according to the assigned treatment. "N" indicates the number of participants with MRI data available for the specified time period.
Arm/Group Title Fingolimod 1.25 mg Fingolimod 0.5 mg Placebo
Hide Arm/Group Description:
Participants received 1.25 mg fingolimod orally once a day for up to 24 months during the core phase. In the Extension phase participants continued to receive 1.25 mg fingolimod orally. Upon implementation of a protocol amendment, all patients taking 1.25 mg fingolimod were switched to 0.5 mg fingolimod orally once a day.
Participants received 0.5 mg fingolimod orally once a day for up to 24 months during the core phase. In the Extension phase participants continued to receive 0.5 mg fingolimod orally once a day.
Participants received placebo capsules orally once a day for up to 24 months during the core phase. In the Extension phase participants received either 1.25 or 0.5 mg fingolimod orally once a day. Upon implementation of a protocol amendment, all patients taking 1.25 mg fingolimod were switched to 0.5 mg fingolimod orally once a day. Upon implementation of a protocol amendment, all patients taking placebo were switched to 0.5 mg fingolimod orally once a day.
Overall Number of Participants Analyzed 370 358 355
Mean (Standard Deviation)
Unit of Measure: lesions
Core Phase (Month 0 to 24) [N=245; 264; 251] 1.6  (5.41) 2.3  (7.26) 8.9  (13.86)
Month 24 to 36 [N=103; 111; 102] 0.63  (2.856) 0.45  (1.360) 0.63  (1.455)
Month 36 to 48 [N=24; 15; 15] 0.13  (0.448) 0.07  (0.258) 2.53  (8.741)
5.Secondary Outcome
Title Number of Gadolinium-enhanced T1 Lesions
Hide Description Inflammatory disease activity was assessed by magnetic resonance imaging (MRI) measurement of the number of gadolinium-enhanced T1 lesions.
Time Frame Month 24 and end of study (up to approximately 54 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Core intent-to-treat (ITT) population: All patients who were randomized in the Core phase and received at least one dose of Core phase drug. "N" indicates the number of participants with evaluable MRI data for the specified time point.
Arm/Group Title Fingolimod 1.25 mg Fingolimod 0.5 mg Placebo
Hide Arm/Group Description:
Participants received 1.25 mg fingolimod orally once a day for up to 24 months during the core phase. In the Extension phase participants continued to receive 1.25 mg fingolimod orally. Upon implementation of a protocol amendment, all patients taking 1.25 mg fingolimod were switched to 0.5 mg fingolimod orally once a day.
Participants received 0.5 mg fingolimod orally once a day for up to 24 months during the core phase. In the Extension phase participants continued to receive 0.5 mg fingolimod orally once a day.
Participants received placebo capsules orally once a day for up to 24 months during the core phase. In the Extension phase participants received either 1.25 or 0.5 mg fingolimod orally once a day. Upon implementation of a protocol amendment, all patients taking 1.25 mg fingolimod were switched to 0.5 mg fingolimod orally once a day. Upon implementation of a protocol amendment, all patients taking placebo were switched to 0.5 mg fingolimod orally once a day.
Overall Number of Participants Analyzed 370 358 355
Mean (Standard Deviation)
Unit of Measure: lesions
Core Phase (Month 24) [N=251; 269; 256] 0.24  (2.395) 0.37  (1.841) 1.22  (2.967)
End of Extension study [N=184; 194; 184] 0.46  (2.381) 0.09  (0.308) 0.45  (3.618)
6.Secondary Outcome
Title Change From Baseline in Lesion Volume at Month 24 (Core Phase)
Hide Description Change from Baseline in lesion volume was measured by MRI for T2 lesions and for T1 hypointense lesions.
Time Frame Baseline and Month 24
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set for whom data were available. N=the number of patients with non-missing baseline and post-baseline values.
Arm/Group Title Fingolimod 1.25 mg Fingolimod 0.5 mg Placebo
Hide Arm/Group Description:
Participants received 1.25 mg fingolimod orally once a day for up to 24 months during the core phase. In the Extension phase participants continued to receive 1.25 mg fingolimod orally. Upon implementation of a protocol amendment, all patients taking 1.25 mg fingolimod were switched to 0.5 mg fingolimod orally once a day.
Participants received 0.5 mg fingolimod orally once a day for up to 24 months during the core phase. In the Extension phase participants continued to receive 0.5 mg fingolimod orally once a day.
Participants received placebo capsules orally once a day for up to 24 months during the core phase. In the Extension phase participants received either 1.25 or 0.5 mg fingolimod orally once a day. Upon implementation of a protocol amendment, all patients taking 1.25 mg fingolimod were switched to 0.5 mg fingolimod orally once a day. Upon implementation of a protocol amendment, all patients taking placebo were switched to 0.5 mg fingolimod orally once a day.
Overall Number of Participants Analyzed 370 358 355
Mean (Standard Deviation)
Unit of Measure: mm^3
T2 lesions [N=248, 266, 251] -436.92  (1557.820) -223.27  (1405.459) 541.83  (2830.868)
T1 hypointense lesions [N=247, 266, 248] -99.13  (391.210) -111.28  (530.961) -37.68  (671.708)
7.Secondary Outcome
Title Percentage of Participants Free of 3-month Confirmed Disability Progression at Month 24 and End of Study
Hide Description Disability progression was defined using the following criteria: One point increase from baseline in patients with Baseline Expanded Disability Status Scale (EDSS) score from 0 to 5.0; or half a point increase from Baseline in patients with Baseline EDSS score of 5.5 or above. A 3-month confirmed disability progression was defined as a 3-month sustained increase from Baseline in EDSS score. The EDSS quantifies disability in multiple sclerosis in 8 functional systems; the score ranges from 0 (normal) to 10 (death due to MS). Progression curves were generated by the Kaplan-Meier method.
Time Frame 24 months and end of study (up to approximately 54 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Core intent-to-treat (ITT) population: All patients who were randomized in the Core phase and received at least one dose of Core phase drug.
Arm/Group Title Fingolimod 1.25 mg Fingolimod 0.5 mg Placebo
Hide Arm/Group Description:
Participants received 1.25 mg fingolimod orally once a day for up to 24 months during the core phase. In the Extension phase participants continued to receive 1.25 mg fingolimod orally. Upon implementation of a protocol amendment, all patients taking 1.25 mg fingolimod were switched to 0.5 mg fingolimod orally once a day.
Participants received 0.5 mg fingolimod orally once a day for up to 24 months during the core phase. In the Extension phase participants continued to receive 0.5 mg fingolimod orally once a day.
Participants received placebo capsules orally once a day for up to 24 months during the core phase. In the Extension phase participants received either 1.25 or 0.5 mg fingolimod orally once a day. Upon implementation of a protocol amendment, all patients taking 1.25 mg fingolimod were switched to 0.5 mg fingolimod orally once a day. Upon implementation of a protocol amendment, all patients taking placebo were switched to 0.5 mg fingolimod orally once a day.
Overall Number of Participants Analyzed 370 358 355
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
At month 24
78.3
(73.74 to 82.87)
74.7
(69.86 to 79.52)
71.0
(65.94 to 76.13)
At end of study
66.64
(59.81 to 73.47)
58.89
(48.98 to 68.80)
63.51
(57.15 to 69.87)
8.Secondary Outcome
Title Percentage of Participants Free of 6-month Confirmed Disability Progression at Month 24 and End of Study
Hide Description Disability progression was defined using the following criteria: One point increase from baseline in patients with Baseline Expanded Disability Status Scale (EDSS) score from 0 to 5.0; or half a point increase from Baseline in patients with Baseline EDSS score of 5.5 or above. A 6-month confirmed disability progression was defined as a 6-month sustained increase from Baseline in EDSS score. The EDSS quantifies disability in multiple sclerosis in 8 functional systems; the score ranges from 0 (normal) to 10 (death due to MS). Progression curves were generated by the Kaplan-Meier method.
Time Frame 24 months and end of study (up to approximately 54 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Core intent-to-treat (ITT) population: All patients who were randomized in the Core phase and received at least one dose of Core phase drug.
Arm/Group Title Fingolimod 1.25 mg Fingolimod 0.5 mg Placebo
Hide Arm/Group Description:
Participants received 1.25 mg fingolimod orally once a day for up to 24 months during the core phase. In the Extension phase participants continued to receive 1.25 mg fingolimod orally. Upon implementation of a protocol amendment, all patients taking 1.25 mg fingolimod were switched to 0.5 mg fingolimod orally once a day.
Participants received 0.5 mg fingolimod orally once a day for up to 24 months during the core phase. In the Extension phase participants continued to receive 0.5 mg fingolimod orally once a day.
Participants received placebo capsules orally once a day for up to 24 months during the core phase. In the Extension phase participants received either 1.25 or 0.5 mg fingolimod orally once a day. Upon implementation of a protocol amendment, all patients taking 1.25 mg fingolimod were switched to 0.5 mg fingolimod orally once a day. Upon implementation of a protocol amendment, all patients taking placebo were switched to 0.5 mg fingolimod orally once a day.
Overall Number of Participants Analyzed 370 358 355
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
At Month 24
86.9
(83.16 to 90.61)
86.2
(82.34 to 89.97)
82.2
(77.90 to 86.44)
At end of study
79.92
(74.43 to 85.41)
74.89
(68.36 to 81.43)
75.03
(69.59 to 80.47)
9.Secondary Outcome
Title Percentage of Participants Relapse-free up to Month 24
Hide Description Estimates of the percentage of participants relapse-free at 24 months were generated from Kaplan-Meier curves of the time to first relapse. A relapse was defined as the appearance of a new neurological abnormality or worsening of previously stable or improving pre-existing neurological abnormality, separated by at least 30 days from onset of a preceding clinical demyelinating event. The abnormality must be present for at least 24 hours and occur in the absence of fever (<37.5C) or infection. A relapse was confirmed by an Independent Evaluating Physician.
Time Frame 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title Fingolimod 1.25 mg Fingolimod 0.5 mg Placebo
Hide Arm/Group Description:
Participants received 1.25 mg fingolimod orally once a day for up to 24 months during the core phase. In the Extension phase participants continued to receive 1.25 mg fingolimod orally. Upon implementation of a protocol amendment, all patients taking 1.25 mg fingolimod were switched to 0.5 mg fingolimod orally once a day.
Participants received 0.5 mg fingolimod orally once a day for up to 24 months during the core phase. In the Extension phase participants continued to receive 0.5 mg fingolimod orally once a day.
Participants received placebo capsules orally once a day for up to 24 months during the core phase. In the Extension phase participants received either 1.25 or 0.5 mg fingolimod orally once a day. Upon implementation of a protocol amendment, all patients taking 1.25 mg fingolimod were switched to 0.5 mg fingolimod orally once a day. Upon implementation of a protocol amendment, all patients taking placebo were switched to 0.5 mg fingolimod orally once a day.
Overall Number of Participants Analyzed 370 358 355
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
73.2
(68.38 to 78.01)
71.5
(66.55 to 76.44)
52.7
(47.20 to 58.24)
10.Secondary Outcome
Title Percentage of Participants Relapse-free up to End of Study
Hide Description Estimates of the percentage of participants relapse-free at end of study were generated from Kaplan-Meier curves of the time to first relapse. A relapse was defined as the appearance of a new neurological abnormality or worsening of previously stable or improving pre-existing neurological abnormality, separated by at least 30 days from onset of a preceding clinical demyelinating event. The abnormality must be present for at least 24 hours and occur in the absence of fever (<37.5C) or infection. A relapse was confirmed by an Independent Evaluating Physician.
Time Frame From Baseline until the end of study (up to approximately 54 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Core intent-to-treat (ITT) population: All patients who were randomized in the Core phase and received at least one dose of Core phase drug.
Arm/Group Title Fingolimod 1.25 mg Fingolimod 0.5 mg Placebo
Hide Arm/Group Description:
Participants received 1.25 mg fingolimod orally once a day for up to 24 months during the core phase. In the Extension phase participants continued to receive 1.25 mg fingolimod orally. Upon implementation of a protocol amendment, all patients taking 1.25 mg fingolimod were switched to 0.5 mg fingolimod orally once a day.
Participants received 0.5 mg fingolimod orally once a day for up to 24 months during the core phase. In the Extension phase participants continued to receive 0.5 mg fingolimod orally once a day.
Participants received placebo capsules orally once a day for up to 24 months during the core phase. In the Extension phase participants received either 1.25 or 0.5 mg fingolimod orally once a day. Upon implementation of a protocol amendment, all patients taking 1.25 mg fingolimod were switched to 0.5 mg fingolimod orally once a day. Upon implementation of a protocol amendment, all patients taking placebo were switched to 0.5 mg fingolimod orally once a day.
Overall Number of Participants Analyzed 370 358 355
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
63.88
(56.19 to 71.57)
66.57
(60.86 to 72.28)
49.12
(43.35 to 54.89)
11.Secondary Outcome
Title Change From Baseline in Multiple Sclerosis Functional Composite (MSFC) Z-score
Hide Description The Multiple Sclerosis Functional Composite (MSFC) is a multidimensional clinical outcome measure that includes quantitative tests of leg function/ambulation (Timed 25-Foot Walk), arm function (9-Hole Peg Test), and cognitive function (Paced Auditory Serial Addition Test). The overall MSFC z-score as an average of the three standardized scores derived using baseline data pooled over each treatment arm as reference population. Higher scores reflect better neurological function and a positive change from Baseline indicates improvement.
Time Frame Baseline, Month 24 and end of study (up to approximately 54 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Core intent-to-treat (ITT) population: All patients who were randomized in the Core phase and received at least one dose of Core phase drug. "N" indicates the number of participants with non-missing data at each time point.
Arm/Group Title Fingolimod 1.25 mg Fingolimod 0.5 mg Placebo
Hide Arm/Group Description:
Participants received 1.25 mg fingolimod orally once a day for up to 24 months during the core phase. In the Extension phase participants continued to receive 1.25 mg fingolimod orally. Upon implementation of a protocol amendment, all patients taking 1.25 mg fingolimod were switched to 0.5 mg fingolimod orally once a day.
Participants received 0.5 mg fingolimod orally once a day for up to 24 months during the core phase. In the Extension phase participants continued to receive 0.5 mg fingolimod orally once a day.
Participants received placebo capsules orally once a day for up to 24 months during the core phase. In the Extension phase participants received either 1.25 or 0.5 mg fingolimod orally once a day. Upon implementation of a protocol amendment, all patients taking 1.25 mg fingolimod were switched to 0.5 mg fingolimod orally once a day. Upon implementation of a protocol amendment, all patients taking placebo were switched to 0.5 mg fingolimod orally once a day.
Overall Number of Participants Analyzed 370 358 355
Mean (Standard Deviation)
Unit of Measure: units on a scale
Month 24 [N=250; 271; 258] -0.08  (0.916) 0.00  (0.600) -0.07  (0.540)
End of Study [N=174; 187; 184] 0.011  (0.3499) -0.091  (0.8770) 0.019  (0.6304)
Time Frame Duration of treatment was up to 24 months during the Core phase, and dependent on the length of patient participation during the Extension phase (up to approximately 54 months overall duration of treatment).
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Core: Fingolimod 1.25 mg Core: Fingolimod 0.5 mg Core: Placebo Extension: Fingolimod 1.25 mg Extension: Fingolimod 0.5 mg
Hide Arm/Group Description Participants received 1.25 mg fingolimod orally once a day for up to 24 months during the core phase. Upon implementation of a protocol amendment, all patients taking 1.25 mg fingolimod were switched to 0.5 mg fingolimod orally once a day. Participants received 0.5 mg fingolimod orally once a day for up to 24 months during the core phase. Participants received placebo capsules orally once a day for up to 24 months during the core phase. Upon implementation of a protocol amendment, all patients taking placebo were switched to 0.5 mg fingolimod orally once a day. Participants received 1.25 mg fingolimod orally once a day in the Extension phase. Upon implementation of a protocol amendment, all patients taking 1.25 mg fingolimod were switched to 0.5 mg fingolimod orally once a day. Participants received 0.5 mg fingolimod orally once a day in the Extension phase.
All-Cause Mortality
Core: Fingolimod 1.25 mg Core: Fingolimod 0.5 mg Core: Placebo Extension: Fingolimod 1.25 mg Extension: Fingolimod 0.5 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/-- 
Hide Serious Adverse Events
Core: Fingolimod 1.25 mg Core: Fingolimod 0.5 mg Core: Placebo Extension: Fingolimod 1.25 mg Extension: Fingolimod 0.5 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   53/370 (14.32%)   53/358 (14.80%)   45/355 (12.68%)   27/308 (8.77%)   21/324 (6.48%) 
Blood and lymphatic system disorders           
Idiopathic thrombocytopenic purpura  1  0/370 (0.00%)  1/358 (0.28%)  0/355 (0.00%)  0/308 (0.00%)  0/324 (0.00%) 
Leukopenia  1  0/370 (0.00%)  1/358 (0.28%)  0/355 (0.00%)  0/308 (0.00%)  0/324 (0.00%) 
Lymphopenia  1  0/370 (0.00%)  1/358 (0.28%)  0/355 (0.00%)  1/308 (0.32%)  1/324 (0.31%) 
Cardiac disorders           
Acute coronary syndrome  1  0/370 (0.00%)  0/358 (0.00%)  0/355 (0.00%)  1/308 (0.32%)  0/324 (0.00%) 
Acute myocardial infarction  1  1/370 (0.27%)  0/358 (0.00%)  0/355 (0.00%)  1/308 (0.32%)  0/324 (0.00%) 
Angina pectoris  1  1/370 (0.27%)  0/358 (0.00%)  2/355 (0.56%)  1/308 (0.32%)  0/324 (0.00%) 
Atrial fibrillation  1  0/370 (0.00%)  1/358 (0.28%)  0/355 (0.00%)  0/308 (0.00%)  0/324 (0.00%) 
Atrioventricular block  1  2/370 (0.54%)  0/358 (0.00%)  0/355 (0.00%)  0/308 (0.00%)  0/324 (0.00%) 
Atrioventricular block first degree  1  0/370 (0.00%)  0/358 (0.00%)  0/355 (0.00%)  1/308 (0.32%)  0/324 (0.00%) 
Atrioventricular block second degree  1  1/370 (0.27%)  0/358 (0.00%)  0/355 (0.00%)  1/308 (0.32%)  0/324 (0.00%) 
Bradycardia  1  6/370 (1.62%)  0/358 (0.00%)  1/355 (0.28%)  2/308 (0.65%)  0/324 (0.00%) 
Cardiac flutter  1  1/370 (0.27%)  0/358 (0.00%)  0/355 (0.00%)  0/308 (0.00%)  0/324 (0.00%) 
Coronary artery disease  1  0/370 (0.00%)  0/358 (0.00%)  0/355 (0.00%)  1/308 (0.32%)  0/324 (0.00%) 
Mitral valve incompetence  1  0/370 (0.00%)  1/358 (0.28%)  0/355 (0.00%)  0/308 (0.00%)  0/324 (0.00%) 
Palpitations  1  1/370 (0.27%)  0/358 (0.00%)  0/355 (0.00%)  0/308 (0.00%)  0/324 (0.00%) 
Pericarditis  1  0/370 (0.00%)  1/358 (0.28%)  0/355 (0.00%)  0/308 (0.00%)  0/324 (0.00%) 
Tricuspid valve incompetence  1  0/370 (0.00%)  1/358 (0.28%)  0/355 (0.00%)  0/308 (0.00%)  0/324 (0.00%) 
Ventricular tachycardia  1  0/370 (0.00%)  1/358 (0.28%)  0/355 (0.00%)  0/308 (0.00%)  0/324 (0.00%) 
Endocrine disorders           
Diabetes insipidus  1  0/370 (0.00%)  0/358 (0.00%)  1/355 (0.28%)  0/308 (0.00%)  0/324 (0.00%) 
Hyperthyroidism  1  0/370 (0.00%)  0/358 (0.00%)  1/355 (0.28%)  0/308 (0.00%)  0/324 (0.00%) 
Eye disorders           
Macular oedema  1  2/370 (0.54%)  1/358 (0.28%)  1/355 (0.28%)  0/308 (0.00%)  0/324 (0.00%) 
Retinal detachment  1  0/370 (0.00%)  1/358 (0.28%)  0/355 (0.00%)  0/308 (0.00%)  1/324 (0.31%) 
Gastrointestinal disorders           
Abdominal hernia  1  0/370 (0.00%)  0/358 (0.00%)  1/355 (0.28%)  0/308 (0.00%)  0/324 (0.00%) 
Abdominal mass  1  0/370 (0.00%)  0/358 (0.00%)  1/355 (0.28%)  0/308 (0.00%)  0/324 (0.00%) 
Abdominal pain  1  1/370 (0.27%)  2/358 (0.56%)  2/355 (0.56%)  0/308 (0.00%)  0/324 (0.00%) 
Abdominal pain lower  1  0/370 (0.00%)  1/358 (0.28%)  1/355 (0.28%)  0/308 (0.00%)  0/324 (0.00%) 
Caecitis  1  0/370 (0.00%)  1/358 (0.28%)  0/355 (0.00%)  0/308 (0.00%)  0/324 (0.00%) 
Constipation  1  0/370 (0.00%)  0/358 (0.00%)  1/355 (0.28%)  0/308 (0.00%)  0/324 (0.00%) 
Diarrhoea  1  0/370 (0.00%)  1/358 (0.28%)  1/355 (0.28%)  0/308 (0.00%)  0/324 (0.00%) 
Gastric disorder  1  0/370 (0.00%)  0/358 (0.00%)  1/355 (0.28%)  0/308 (0.00%)  0/324 (0.00%) 
Hiatus hernia  1  0/370 (0.00%)  0/358 (0.00%)  1/355 (0.28%)  0/308 (0.00%)  0/324 (0.00%) 
Intestinal obstruction  1  0/370 (0.00%)  0/358 (0.00%)  1/355 (0.28%)  0/308 (0.00%)  0/324 (0.00%) 
Large intestine perforation  1  0/370 (0.00%)  0/358 (0.00%)  1/355 (0.28%)  0/308 (0.00%)  0/324 (0.00%) 
Vomiting  1  0/370 (0.00%)  1/358 (0.28%)  0/355 (0.00%)  0/308 (0.00%)  0/324 (0.00%) 
General disorders           
Asthenia  1  1/370 (0.27%)  0/358 (0.00%)  0/355 (0.00%)  0/308 (0.00%)  0/324 (0.00%) 
Chest discomfort  1  1/370 (0.27%)  0/358 (0.00%)  0/355 (0.00%)  0/308 (0.00%)  0/324 (0.00%) 
Chest pain  1  1/370 (0.27%)  1/358 (0.28%)  0/355 (0.00%)  0/308 (0.00%)  1/324 (0.31%) 
Fatigue  1  1/370 (0.27%)  0/358 (0.00%)  0/355 (0.00%)  0/308 (0.00%)  0/324 (0.00%) 
Non-cardiac chest pain  1  0/370 (0.00%)  2/358 (0.56%)  0/355 (0.00%)  0/308 (0.00%)  0/324 (0.00%) 
Pelvic mass  1  1/370 (0.27%)  0/358 (0.00%)  0/355 (0.00%)  0/308 (0.00%)  0/324 (0.00%) 
Pyrexia  1  1/370 (0.27%)  0/358 (0.00%)  0/355 (0.00%)  0/308 (0.00%)  0/324 (0.00%) 
Hepatobiliary disorders           
Bile duct stone  1  1/370 (0.27%)  0/358 (0.00%)  0/355 (0.00%)  0/308 (0.00%)  0/324 (0.00%) 
Cholecystitis  1  2/370 (0.54%)  0/358 (0.00%)  1/355 (0.28%)  0/308 (0.00%)  0/324 (0.00%) 
Cholelithiasis  1  0/370 (0.00%)  1/358 (0.28%)  2/355 (0.56%)  0/308 (0.00%)  1/324 (0.31%) 
Jaundice  1  1/370 (0.27%)  0/358 (0.00%)  0/355 (0.00%)  0/308 (0.00%)  0/324 (0.00%) 
Immune system disorders           
Drug hypersensitivity  1  0/370 (0.00%)  0/358 (0.00%)  1/355 (0.28%)  0/308 (0.00%)  0/324 (0.00%) 
Infections and infestations           
Acute sinusitis  1  1/370 (0.27%)  0/358 (0.00%)  0/355 (0.00%)  0/308 (0.00%)  0/324 (0.00%) 
Appendicitis  1  0/370 (0.00%)  2/358 (0.56%)  1/355 (0.28%)  1/308 (0.32%)  0/324 (0.00%) 
Bartholin's abscess  1  0/370 (0.00%)  0/358 (0.00%)  0/355 (0.00%)  1/308 (0.32%)  0/324 (0.00%) 
Bronchitis  1  0/370 (0.00%)  1/358 (0.28%)  1/355 (0.28%)  0/308 (0.00%)  1/324 (0.31%) 
Cellulitis  1  1/370 (0.27%)  0/358 (0.00%)  0/355 (0.00%)  0/308 (0.00%)  0/324 (0.00%) 
Diverticulitis  1  1/370 (0.27%)  0/358 (0.00%)  0/355 (0.00%)  0/308 (0.00%)  0/324 (0.00%) 
Encephalitis herpes  1  1/370 (0.27%)  0/358 (0.00%)  0/355 (0.00%)  0/308 (0.00%)  0/324 (0.00%) 
Gastritis viral  1  0/370 (0.00%)  0/358 (0.00%)  0/355 (0.00%)  1/308 (0.32%)  0/324 (0.00%) 
Gastroenteritis  1  1/370 (0.27%)  0/358 (0.00%)  0/355 (0.00%)  1/308 (0.32%)  0/324 (0.00%) 
Gastroenteritis viral  1  0/370 (0.00%)  0/358 (0.00%)  1/355 (0.28%)  0/308 (0.00%)  0/324 (0.00%) 
Hepatitis C  1  1/370 (0.27%)  0/358 (0.00%)  0/355 (0.00%)  0/308 (0.00%)  0/324 (0.00%) 
Herpes zoster  1  0/370 (0.00%)  1/358 (0.28%)  0/355 (0.00%)  0/308 (0.00%)  0/324 (0.00%) 
Herpes zoster disseminated  1  1/370 (0.27%)  0/358 (0.00%)  0/355 (0.00%)  0/308 (0.00%)  0/324 (0.00%) 
Kidney infection  1  0/370 (0.00%)  1/358 (0.28%)  0/355 (0.00%)  0/308 (0.00%)  0/324 (0.00%) 
Labyrinthitis  1  0/370 (0.00%)  0/358 (0.00%)  1/355 (0.28%)  0/308 (0.00%)  0/324 (0.00%) 
Lower respiratory tract infection fungal  1  0/370 (0.00%)  1/358 (0.28%)  0/355 (0.00%)  0/308 (0.00%)  0/324 (0.00%) 
Lyme disease  1  0/370 (0.00%)  0/358 (0.00%)  1/355 (0.28%)  0/308 (0.00%)  0/324 (0.00%) 
Mastoiditis  1  0/370 (0.00%)  1/358 (0.28%)  0/355 (0.00%)  0/308 (0.00%)  0/324 (0.00%) 
Otitis media  1  0/370 (0.00%)  1/358 (0.28%)  0/355 (0.00%)  0/308 (0.00%)  0/324 (0.00%) 
Pneumonia  1  0/370 (0.00%)  1/358 (0.28%)  0/355 (0.00%)  0/308 (0.00%)  1/324 (0.31%) 
Post procedural infection  1  0/370 (0.00%)  0/358 (0.00%)  0/355 (0.00%)  1/308 (0.32%)  0/324 (0.00%) 
Pyelonephritis  1  1/370 (0.27%)  0/358 (0.00%)  0/355 (0.00%)  0/308 (0.00%)  0/324 (0.00%) 
Sinusitis  1  0/370 (0.00%)  2/358 (0.56%)  0/355 (0.00%)  0/308 (0.00%)  0/324 (0.00%) 
Staphylococcal abscess  1  0/370 (0.00%)  1/358 (0.28%)  0/355 (0.00%)  0/308 (0.00%)  0/324 (0.00%) 
Staphylococcal infection  1  0/370 (0.00%)  1/358 (0.28%)  0/355 (0.00%)  0/308 (0.00%)  0/324 (0.00%) 
Urinary tract infection  1  0/370 (0.00%)  1/358 (0.28%)  1/355 (0.28%)  1/308 (0.32%)  0/324 (0.00%) 
Vulvitis  1  0/370 (0.00%)  1/358 (0.28%)  0/355 (0.00%)  0/308 (0.00%)  0/324 (0.00%) 
Injury, poisoning and procedural complications           
Ankle fracture  1  1/370 (0.27%)  0/358 (0.00%)  1/355 (0.28%)  0/308 (0.00%)  0/324 (0.00%) 
Drug exposure during pregnancy  1  0/370 (0.00%)  1/358 (0.28%)  0/355 (0.00%)  0/308 (0.00%)  0/324 (0.00%) 
Injury  1  0/370 (0.00%)  0/358 (0.00%)  0/355 (0.00%)  1/308 (0.32%)  0/324 (0.00%) 
Joint dislocation  1  0/370 (0.00%)  0/358 (0.00%)  0/355 (0.00%)  0/308 (0.00%)  1/324 (0.31%) 
Laceration  1  1/370 (0.27%)  0/358 (0.00%)  0/355 (0.00%)  0/308 (0.00%)  0/324 (0.00%) 
Lower limb fracture  1  0/370 (0.00%)  0/358 (0.00%)  0/355 (0.00%)  1/308 (0.32%)  1/324 (0.31%) 
Overdose  1  0/370 (0.00%)  0/358 (0.00%)  1/355 (0.28%)  0/308 (0.00%)  1/324 (0.31%) 
Post procedural haemorrhage  1  0/370 (0.00%)  0/358 (0.00%)  0/355 (0.00%)  0/308 (0.00%)  1/324 (0.31%) 
Toxicity to various agents  1  0/370 (0.00%)  0/358 (0.00%)  1/355 (0.28%)  0/308 (0.00%)  0/324 (0.00%) 
Investigations           
Alanine aminotransferase increased  1  1/370 (0.27%)  0/358 (0.00%)  0/355 (0.00%)  0/308 (0.00%)  0/324 (0.00%) 
Hepatic enzyme increased  1  1/370 (0.27%)  0/358 (0.00%)  0/355 (0.00%)  0/308 (0.00%)  0/324 (0.00%) 
Metabolism and nutrition disorders           
Dehydration  1  0/370 (0.00%)  0/358 (0.00%)  1/355 (0.28%)  0/308 (0.00%)  1/324 (0.31%) 
Hypokalaemia  1  0/370 (0.00%)  1/358 (0.28%)  1/355 (0.28%)  0/308 (0.00%)  0/324 (0.00%) 
Hyponatraemia  1  1/370 (0.27%)  0/358 (0.00%)  0/355 (0.00%)  1/308 (0.32%)  0/324 (0.00%) 
Hypophosphataemia  1  0/370 (0.00%)  0/358 (0.00%)  1/355 (0.28%)  0/308 (0.00%)  0/324 (0.00%) 
Metabolic acidosis  1  0/370 (0.00%)  1/358 (0.28%)  0/355 (0.00%)  0/308 (0.00%)  0/324 (0.00%) 
Musculoskeletal and connective tissue disorders           
Arthralgia  1  0/370 (0.00%)  0/358 (0.00%)  1/355 (0.28%)  0/308 (0.00%)  0/324 (0.00%) 
Back pain  1  1/370 (0.27%)  0/358 (0.00%)  0/355 (0.00%)  0/308 (0.00%)  0/324 (0.00%) 
Intervertebral disc degeneration  1  0/370 (0.00%)  0/358 (0.00%)  1/355 (0.28%)  0/308 (0.00%)  0/324 (0.00%) 
Intervertebral disc protrusion  1  0/370 (0.00%)  0/358 (0.00%)  1/355 (0.28%)  0/308 (0.00%)  0/324 (0.00%) 
Mobility decreased  1  1/370 (0.27%)  0/358 (0.00%)  0/355 (0.00%)  0/308 (0.00%)  0/324 (0.00%) 
Morphoea  1  1/370 (0.27%)  0/358 (0.00%)  0/355 (0.00%)  0/308 (0.00%)  0/324 (0.00%) 
Musculoskeletal chest pain  1  0/370 (0.00%)  0/358 (0.00%)  0/355 (0.00%)  0/308 (0.00%)  1/324 (0.31%) 
Myalgia  1  0/370 (0.00%)  1/358 (0.28%)  0/355 (0.00%)  0/308 (0.00%)  0/324 (0.00%) 
Neck pain  1  1/370 (0.27%)  0/358 (0.00%)  0/355 (0.00%)  1/308 (0.32%)  0/324 (0.00%) 
Spinal column stenosis  1  1/370 (0.27%)  0/358 (0.00%)  0/355 (0.00%)  0/308 (0.00%)  0/324 (0.00%) 
Spinal osteoarthritis  1  0/370 (0.00%)  0/358 (0.00%)  1/355 (0.28%)  0/308 (0.00%)  0/324 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)           
Astrocytoma  1  1/370 (0.27%)  0/358 (0.00%)  0/355 (0.00%)  0/308 (0.00%)  0/324 (0.00%) 
Basal cell carcinoma  1  6/370 (1.62%)  9/358 (2.51%)  2/355 (0.56%)  0/308 (0.00%)  1/324 (0.31%) 
Breast cancer  1  0/370 (0.00%)  1/358 (0.28%)  0/355 (0.00%)  1/308 (0.32%)  1/324 (0.31%) 
Colon cancer  1  0/370 (0.00%)  0/358 (0.00%)  1/355 (0.28%)  0/308 (0.00%)  0/324 (0.00%) 
Dysplastic naevus  1  0/370 (0.00%)  0/358 (0.00%)  0/355 (0.00%)  1/308 (0.32%)  0/324 (0.00%) 
Endometrial cancer  1  0/370 (0.00%)  0/358 (0.00%)  0/355 (0.00%)  1/308 (0.32%)  0/324 (0.00%) 
Ependymoma  1  1/370 (0.27%)  0/358 (0.00%)  0/355 (0.00%)  0/308 (0.00%)  0/324 (0.00%) 
Hair follicle tumour benign  1  1/370 (0.27%)  0/358 (0.00%)  0/355 (0.00%)  0/308 (0.00%)  0/324 (0.00%) 
Malignant melanoma in situ  1  0/370 (0.00%)  1/358 (0.28%)  0/355 (0.00%)  0/308 (0.00%)  0/324 (0.00%) 
Melanocytic naevus  1  1/370 (0.27%)  0/358 (0.00%)  0/355 (0.00%)  0/308 (0.00%)  1/324 (0.31%) 
Parathyroid tumour benign  1  0/370 (0.00%)  0/358 (0.00%)  0/355 (0.00%)  0/308 (0.00%)  1/324 (0.31%) 
Sarcoma of skin  1  0/370 (0.00%)  1/358 (0.28%)  0/355 (0.00%)  0/308 (0.00%)  0/324 (0.00%) 
Squamous cell carcinoma  1  3/370 (0.81%)  1/358 (0.28%)  2/355 (0.56%)  1/308 (0.32%)  1/324 (0.31%) 
Squamous cell carcinoma of skin  1  0/370 (0.00%)  0/358 (0.00%)  0/355 (0.00%)  1/308 (0.32%)  0/324 (0.00%) 
T-cell lymphoma  1  1/370 (0.27%)  0/358 (0.00%)  0/355 (0.00%)  0/308 (0.00%)  0/324 (0.00%) 
Thyroid adenoma  1  0/370 (0.00%)  0/358 (0.00%)  0/355 (0.00%)  1/308 (0.32%)  0/324 (0.00%) 
Thyroid cancer  1  0/370 (0.00%)  1/358 (0.28%)  1/355 (0.28%)  0/308 (0.00%)  0/324 (0.00%) 
Uterine leiomyoma  1  1/370 (0.27%)  0/358 (0.00%)  2/355 (0.56%)  1/308 (0.32%)  0/324 (0.00%) 
Nervous system disorders           
Akathisia  1  0/370 (0.00%)  0/358 (0.00%)  1/355 (0.28%)  0/308 (0.00%)  0/324 (0.00%) 
Convulsion  1  0/370 (0.00%)  3/358 (0.84%)  1/355 (0.28%)  0/308 (0.00%)  0/324 (0.00%) 
Encephalitis  1  0/370 (0.00%)  1/358 (0.28%)  1/355 (0.28%)  0/308 (0.00%)  0/324 (0.00%) 
Encephalopathy  1  2/370 (0.54%)  0/358 (0.00%)  0/355 (0.00%)  0/308 (0.00%)  0/324 (0.00%) 
Grand mal convulsion  1  0/370 (0.00%)  0/358 (0.00%)  1/355 (0.28%)  0/308 (0.00%)  0/324 (0.00%) 
Haemorrhagic stroke  1  1/370 (0.27%)  0/358 (0.00%)  0/355 (0.00%)  0/308 (0.00%)  0/324 (0.00%) 
Headache  1  0/370 (0.00%)  0/358 (0.00%)  1/355 (0.28%)  1/308 (0.32%)  0/324 (0.00%) 
Intracranial aneurysm  1  0/370 (0.00%)  0/358 (0.00%)  0/355 (0.00%)  1/308 (0.32%)  0/324 (0.00%) 
Migraine  1  1/370 (0.27%)  1/358 (0.28%)  2/355 (0.56%)  1/308 (0.32%)  0/324 (0.00%) 
Multiple sclerosis relapse  1  2/370 (0.54%)  1/358 (0.28%)  3/355 (0.85%)  2/308 (0.65%)  5/324 (1.54%) 
Optic neuritis  1  0/370 (0.00%)  0/358 (0.00%)  1/355 (0.28%)  0/308 (0.00%)  0/324 (0.00%) 
Sciatica  1  1/370 (0.27%)  0/358 (0.00%)  0/355 (0.00%)  0/308 (0.00%)  0/324 (0.00%) 
Simple partial seizures  1  1/370 (0.27%)  0/358 (0.00%)  0/355 (0.00%)  0/308 (0.00%)  0/324 (0.00%) 
Status epilepticus  1  1/370 (0.27%)  1/358 (0.28%)  0/355 (0.00%)  0/308 (0.00%)  0/324 (0.00%) 
Syncope  1  2/370 (0.54%)  2/358 (0.56%)  1/355 (0.28%)  1/308 (0.32%)  1/324 (0.31%) 
Transient ischaemic attack  1  0/370 (0.00%)  0/358 (0.00%)  1/355 (0.28%)  0/308 (0.00%)  0/324 (0.00%) 
Pregnancy, puerperium and perinatal conditions           
Abortion  1  0/370 (0.00%)  0/358 (0.00%)  1/355 (0.28%)  0/308 (0.00%)  0/324 (0.00%) 
Abortion spontaneous  1  0/370 (0.00%)  1/358 (0.28%)  0/355 (0.00%)  1/308 (0.32%)  0/324 (0.00%) 
Ectopic pregnancy  1  1/370 (0.27%)  0/358 (0.00%)  0/355 (0.00%)  0/308 (0.00%)  0/324 (0.00%) 
Psychiatric disorders           
Acute psychosis  1  0/370 (0.00%)  0/358 (0.00%)  1/355 (0.28%)  0/308 (0.00%)  0/324 (0.00%) 
Aggression  1  1/370 (0.27%)  0/358 (0.00%)  0/355 (0.00%)  0/308 (0.00%)  0/324 (0.00%) 
Anxiety  1  1/370 (0.27%)  0/358 (0.00%)  1/355 (0.28%)  0/308 (0.00%)  0/324 (0.00%) 
Confusional state  1  1/370 (0.27%)  0/358 (0.00%)  0/355 (0.00%)  0/308 (0.00%)  0/324 (0.00%) 
Depression  1  1/370 (0.27%)  0/358 (0.00%)  2/355 (0.56%)  0/308 (0.00%)  0/324 (0.00%) 
Drug dependence  1  0/370 (0.00%)  0/358 (0.00%)  1/355 (0.28%)  0/308 (0.00%)  0/324 (0.00%) 
Frustration  1  0/370 (0.00%)  0/358 (0.00%)  1/355 (0.28%)  0/308 (0.00%)  0/324 (0.00%) 
Hallucination  1  0/370 (0.00%)  0/358 (0.00%)  0/355 (0.00%)  1/308 (0.32%)  0/324 (0.00%) 
Major depression  1  0/370 (0.00%)  1/358 (0.28%)  3/355 (0.85%)  0/308 (0.00%)  0/324 (0.00%) 
Mania  1  1/370 (0.27%)  0/358 (0.00%)  0/355 (0.00%)  0/308 (0.00%)  0/324 (0.00%) 
Mental disorder  1  0/370 (0.00%)  0/358 (0.00%)  2/355 (0.56%)  0/308 (0.00%)  0/324 (0.00%) 
Mental status changes  1  0/370 (0.00%)  0/358 (0.00%)  1/355 (0.28%)  0/308 (0.00%)  0/324 (0.00%) 
Paranoia  1  1/370 (0.27%)  0/358 (0.00%)  0/355 (0.00%)  0/308 (0.00%)  0/324 (0.00%) 
Suicidal behaviour  1  0/370 (0.00%)  0/358 (0.00%)  1/355 (0.28%)  0/308 (0.00%)  0/324 (0.00%) 
Suicidal ideation  1  1/370 (0.27%)  0/358 (0.00%)  1/355 (0.28%)  1/308 (0.32%)  0/324 (0.00%) 
Renal and urinary disorders           
Chromaturia  1  1/370 (0.27%)  0/358 (0.00%)  0/355 (0.00%)  0/308 (0.00%)  0/324 (0.00%) 
Nephrolithiasis  1  0/370 (0.00%)  3/358 (0.84%)  0/355 (0.00%)  0/308 (0.00%)  0/324 (0.00%) 
Renal colic  1  0/370 (0.00%)  1/358 (0.28%)  0/355 (0.00%)  0/308 (0.00%)  0/324 (0.00%) 
Reproductive system and breast disorders           
Adenomyosis  1  0/370 (0.00%)  1/358 (0.28%)  0/355 (0.00%)  0/308 (0.00%)  0/324 (0.00%) 
Cervical cyst  1  0/370 (0.00%)  0/358 (0.00%)  0/355 (0.00%)  1/308 (0.32%)  0/324 (0.00%) 
Cervical dysplasia  1  0/370 (0.00%)  0/358 (0.00%)  0/355 (0.00%)  0/308 (0.00%)  1/324 (0.31%) 
Cystocele  1  0/370 (0.00%)  1/358 (0.28%)  0/355 (0.00%)  0/308 (0.00%)  0/324 (0.00%) 
Haemorrhagic ovarian cyst  1  0/370 (0.00%)  1/358 (0.28%)  0/355 (0.00%)  0/308 (0.00%)  0/324 (0.00%) 
Menorrhagia  1  0/370 (0.00%)  0/358 (0.00%)  1/355 (0.28%)  1/308 (0.32%)  0/324 (0.00%) 
Ovarian cyst  1  1/370 (0.27%)  0/358 (0.00%)  0/355 (0.00%)  0/308 (0.00%)  0/324 (0.00%) 
Pelvic pain  1  0/370 (0.00%)  0/358 (0.00%)  1/355 (0.28%)  0/308 (0.00%)  0/324 (0.00%) 
Rectocele  1  0/370 (0.00%)  1/358 (0.28%)  0/355 (0.00%)  0/308 (0.00%)  0/324 (0.00%) 
Uterine prolapse  1  0/370 (0.00%)  0/358 (0.00%)  2/355 (0.56%)  0/308 (0.00%)  0/324 (0.00%) 
Uterovaginal prolapse  1  0/370 (0.00%)  1/358 (0.28%)  0/355 (0.00%)  0/308 (0.00%)  0/324 (0.00%) 
Vaginal haemorrhage  1  1/370 (0.27%)  0/358 (0.00%)  0/355 (0.00%)  0/308 (0.00%)  0/324 (0.00%) 
Respiratory, thoracic and mediastinal disorders           
Asthma  1  1/370 (0.27%)  0/358 (0.00%)  0/355 (0.00%)  0/308 (0.00%)  0/324 (0.00%) 
Bronchospasm  1  0/370 (0.00%)  1/358 (0.28%)  0/355 (0.00%)  0/308 (0.00%)  0/324 (0.00%) 
Dyspnoea  1  1/370 (0.27%)  1/358 (0.28%)  0/355 (0.00%)  0/308 (0.00%)  0/324 (0.00%) 
Pulmonary embolism  1  1/370 (0.27%)  1/358 (0.28%)  0/355 (0.00%)  0/308 (0.00%)  0/324 (0.00%) 
Wheezing  1  1/370 (0.27%)  0/358 (0.00%)  0/355 (0.00%)  0/308 (0.00%)  0/324 (0.00%) 
Skin and subcutaneous tissue disorders           
Urticaria  1  0/370 (0.00%)  0/358 (0.00%)  1/355 (0.28%)  0/308 (0.00%)  0/324 (0.00%) 
Surgical and medical procedures           
Abortion induced  1  1/370 (0.27%)  0/358 (0.00%)  0/355 (0.00%)  1/308 (0.32%)  0/324 (0.00%) 
Vascular disorders           
Aortic dissection  1  0/370 (0.00%)  0/358 (0.00%)  1/355 (0.28%)  0/308 (0.00%)  0/324 (0.00%) 
Embolism  1  1/370 (0.27%)  0/358 (0.00%)  0/355 (0.00%)  0/308 (0.00%)  0/324 (0.00%) 
Haemorrhage  1  1/370 (0.27%)  0/358 (0.00%)  0/355 (0.00%)  0/308 (0.00%)  0/324 (0.00%) 
Hypertension  1  1/370 (0.27%)  0/358 (0.00%)  0/355 (0.00%)  0/308 (0.00%)  0/324 (0.00%) 
Orthostatic hypotension  1  0/370 (0.00%)  0/358 (0.00%)  0/355 (0.00%)  0/308 (0.00%)  1/324 (0.31%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Core: Fingolimod 1.25 mg Core: Fingolimod 0.5 mg Core: Placebo Extension: Fingolimod 1.25 mg Extension: Fingolimod 0.5 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   335/370 (90.54%)   320/358 (89.39%)   305/355 (85.92%)   216/308 (70.13%)   223/324 (68.83%) 
Blood and lymphatic system disorders           
Lymphopenia  1  36/370 (9.73%)  26/358 (7.26%)  0/355 (0.00%)  25/308 (8.12%)  19/324 (5.86%) 
Eye disorders           
Vision blurred  1  8/370 (2.16%)  18/358 (5.03%)  12/355 (3.38%)  4/308 (1.30%)  8/324 (2.47%) 
Gastrointestinal disorders           
Abdominal pain upper  1  9/370 (2.43%)  18/358 (5.03%)  7/355 (1.97%)  3/308 (0.97%)  2/324 (0.62%) 
Diarrhoea  1  52/370 (14.05%)  48/358 (13.41%)  43/355 (12.11%)  13/308 (4.22%)  16/324 (4.94%) 
Dyspepsia  1  18/370 (4.86%)  12/358 (3.35%)  18/355 (5.07%)  4/308 (1.30%)  3/324 (0.93%) 
Nausea  1  57/370 (15.41%)  63/358 (17.60%)  54/355 (15.21%)  13/308 (4.22%)  14/324 (4.32%) 
Vomiting  1  29/370 (7.84%)  21/358 (5.87%)  27/355 (7.61%)  6/308 (1.95%)  8/324 (2.47%) 
General disorders           
Fatigue  1  29/370 (7.84%)  22/358 (6.15%)  25/355 (7.04%)  12/308 (3.90%)  3/324 (0.93%) 
Pain  1  21/370 (5.68%)  10/358 (2.79%)  15/355 (4.23%)  8/308 (2.60%)  7/324 (2.16%) 
Pyrexia  1  16/370 (4.32%)  14/358 (3.91%)  20/355 (5.63%)  2/308 (0.65%)  5/324 (1.54%) 
Infections and infestations           
Bronchitis  1  34/370 (9.19%)  29/358 (8.10%)  20/355 (5.63%)  18/308 (5.84%)  19/324 (5.86%) 
Influenza  1  26/370 (7.03%)  34/358 (9.50%)  24/355 (6.76%)  11/308 (3.57%)  11/324 (3.40%) 
Nasopharyngitis  1  88/370 (23.78%)  84/358 (23.46%)  85/355 (23.94%)  50/308 (16.23%)  52/324 (16.05%) 
Sinusitis  1  45/370 (12.16%)  55/358 (15.36%)  45/355 (12.68%)  31/308 (10.06%)  27/324 (8.33%) 
Upper respiratory tract infection  1  92/370 (24.86%)  87/358 (24.30%)  86/355 (24.23%)  49/308 (15.91%)  40/324 (12.35%) 
Urinary tract infection  1  45/370 (12.16%)  47/358 (13.13%)  54/355 (15.21%)  23/308 (7.47%)  24/324 (7.41%) 
Injury, poisoning and procedural complications           
Fall  1  16/370 (4.32%)  22/358 (6.15%)  16/355 (4.51%)  14/308 (4.55%)  11/324 (3.40%) 
Investigations           
Alanine aminotransferase increased  1  35/370 (9.46%)  29/358 (8.10%)  6/355 (1.69%)  4/308 (1.30%)  13/324 (4.01%) 
Gamma-glutamyltransferase increased  1  21/370 (5.68%)  23/358 (6.42%)  2/355 (0.56%)  2/308 (0.65%)  8/324 (2.47%) 
Lymphocyte count decreased  1  20/370 (5.41%)  13/358 (3.63%)  0/355 (0.00%)  16/308 (5.19%)  20/324 (6.17%) 
Musculoskeletal and connective tissue disorders           
Arthralgia  1  36/370 (9.73%)  30/358 (8.38%)  38/355 (10.70%)  15/308 (4.87%)  10/324 (3.09%) 
Back pain  1  34/370 (9.19%)  29/358 (8.10%)  39/355 (10.99%)  20/308 (6.49%)  17/324 (5.25%) 
Neck pain  1  21/370 (5.68%)  14/358 (3.91%)  16/355 (4.51%)  5/308 (1.62%)  7/324 (2.16%) 
Pain in extremity  1  36/370 (9.73%)  44/358 (12.29%)  27/355 (7.61%)  20/308 (6.49%)  8/324 (2.47%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)           
Melanocytic naevus  1  33/370 (8.92%)  38/358 (10.61%)  44/355 (12.39%)  18/308 (5.84%)  21/324 (6.48%) 
Nervous system disorders           
Dizziness  1  53/370 (14.32%)  38/358 (10.61%)  43/355 (12.11%)  10/308 (3.25%)  11/324 (3.40%) 
Headache  1  81/370 (21.89%)  83/358 (23.18%)  76/355 (21.41%)  25/308 (8.12%)  29/324 (8.95%) 
Migraine  1  15/370 (4.05%)  24/358 (6.70%)  19/355 (5.35%)  2/308 (0.65%)  8/324 (2.47%) 
Paraesthesia  1  14/370 (3.78%)  19/358 (5.31%)  18/355 (5.07%)  5/308 (1.62%)  5/324 (1.54%) 
Psychiatric disorders           
Anxiety  1  18/370 (4.86%)  18/358 (5.03%)  17/355 (4.79%)  5/308 (1.62%)  5/324 (1.54%) 
Depression  1  34/370 (9.19%)  29/358 (8.10%)  32/355 (9.01%)  11/308 (3.57%)  13/324 (4.01%) 
Insomnia  1  24/370 (6.49%)  31/358 (8.66%)  24/355 (6.76%)  2/308 (0.65%)  6/324 (1.85%) 
Respiratory, thoracic and mediastinal disorders           
Cough  1  51/370 (13.78%)  52/358 (14.53%)  53/355 (14.93%)  23/308 (7.47%)  24/324 (7.41%) 
Dyspnoea  1  46/370 (12.43%)  34/358 (9.50%)  33/355 (9.30%)  6/308 (1.95%)  6/324 (1.85%) 
Nasal congestion  1  23/370 (6.22%)  17/358 (4.75%)  21/355 (5.92%)  7/308 (2.27%)  6/324 (1.85%) 
Oropharyngeal pain  1  25/370 (6.76%)  29/358 (8.10%)  32/355 (9.01%)  12/308 (3.90%)  9/324 (2.78%) 
Skin and subcutaneous tissue disorders           
Rash  1  21/370 (5.68%)  22/358 (6.15%)  24/355 (6.76%)  14/308 (4.55%)  12/324 (3.70%) 
Vascular disorders           
Hypertension  1  46/370 (12.43%)  32/358 (8.94%)  11/355 (3.10%)  11/308 (3.57%)  6/324 (1.85%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
Phone: 862-778-8300
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Novartis
ClinicalTrials.gov Identifier: NCT00355134    
Obsolete Identifiers: NCT00774670
Other Study ID Numbers: CFTY720D2309
First Submitted: July 19, 2006
First Posted: July 21, 2006
Results First Submitted: May 23, 2012
Results First Posted: June 26, 2012
Last Update Posted: August 7, 2012