Trial Outcomes & Findings for Fingolimod Versus Interferon Beta 1b in Cognitive Symptoms (NCT NCT01333501)

NCT ID: NCT01333501

Last Updated: 2017-03-21

Results Overview

Brief Repeatable Battery (BRB)- widely used as a clinical and research tool, with 68% sensitivity and 85% specificity. It consists of the serial administration of 5 tests. One of the tests is SRT (Selective Reminding Test) for episodic memory (verbal learning and delayed recall). A word recalled on two consecutive trials is considered to have entered long-term storage (LTS) on the first of these trials and scored as LTS on all following trials. The total of the words in LTS of all six trials is then summed. The total score ranged from 0 to 72. Higher values represent a better outcome.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 151 participants
• Primary outcome timeframe: Screening (-1month), 18 month
• Results posted on: 2017-03-21

Participant Flow

Total patients randomized in the study (157). Patients who took at least one dose of study drug are 151. The study there were 6 patients who were enrolled but who never took any dose of study drug.

Participant milestones

Measure	Fingolimod 0.5 mg in capsules for oral administration once daily	Interferon Beta 1b 250 μg injected s.c. every other day
Overall Study STARTED	106	51
Overall Study Full Analysis Set (FAS)	80	28
Overall Study Safety Population	104	47
Overall Study COMPLETED	97	30
Overall Study NOT COMPLETED	9	21

Reasons for withdrawal

Measure	Fingolimod 0.5 mg in capsules for oral administration once daily	Interferon Beta 1b 250 μg injected s.c. every other day
Overall Study Adverse Event	3	1
Overall Study Abnormal laboratory value	2	1
Overall Study Unsatisfactory therapeutic effect	1	7
Overall Study Withdrawn consent	3	12

Baseline Characteristics

Fingolimod Versus Interferon Beta 1b in Cognitive Symptoms

Baseline characteristics by cohort

Measure	Fingolimod n=104 Participants 0.5 mg in capsules for oral administration once daily	Interferon Beta 1b n=47 Participants 250 μg injected s.c. every other day	Total n=151 Participants Total of all reporting groups
Age, Continuous	39.53 Years STANDARD_DEVIATION 9.28 • n=5 Participants	37.53 Years STANDARD_DEVIATION 9.27 • n=7 Participants	38.91 Years STANDARD_DEVIATION 9.29 • n=5 Participants
Sex: Female, Male Female	68 Participants n=5 Participants	30 Participants n=7 Participants	98 Participants n=5 Participants
Sex: Female, Male Male	36 Participants n=5 Participants	17 Participants n=7 Participants	53 Participants n=5 Participants

PRIMARY outcome

Timeframe: Screening (-1month), 18 month

Population: Full analysis set (FAS) - all randomized patients who received at least one dose of study drug and had at least one post-baseline assessment of both primary efficacy variables (i.e. non-missing information about the BRB and DKEFS - Sorting test) without any major protocol violations.

Brief Repeatable Battery (BRB)- widely used as a clinical and research tool, with 68% sensitivity and 85% specificity. It consists of the serial administration of 5 tests. One of the tests is SRT (Selective Reminding Test) for episodic memory (verbal learning and delayed recall). A word recalled on two consecutive trials is considered to have entered long-term storage (LTS) on the first of these trials and scored as LTS on all following trials. The total of the words in LTS of all six trials is then summed. The total score ranged from 0 to 72. Higher values represent a better outcome.

Outcome measures

Measure	Fingolimod n=80 Participants 0.5 mg in capsules for oral administration once daily	Interferon Beta 1b n=28 Participants 250 μg injected s.c. every other day
Change From Screening in Selective Reminding Test - Long-Term Storage (SRT-LTS) Raw Score	6.32 raw score Standard Error 1.33	4.46 raw score Standard Error 2.28

PRIMARY outcome

Timeframe: Screening (-1month), 18 month

Population: Full analysis set (FAS) - all randomized patients who received at least one dose of study drug and had at least one post-baseline assessment of both primary efficacy variables (i.e. non-missing information about the BRB and DKEFS - Sorting test) without any major protocol violations.

Brief Repeatable Battery (BRB)- widely used as a clinical and research tool, with 68% sensitivity and 85% specificity. It consists of the serial administration of 5 tests. One of the tests is SRT (Selective Reminding Test) for episodic memory (verbal learning and delayed recall). A word recalled on two consecutive trials is considered to have entered long-term storage (LTS) on the first of these trials and scored as LTS on all following trials. The total of the words in LTS of all six trials is then summed. If a word in LTS is consistently recalled on all subsequent trials, it is then scored as Consistent Long Term Retrieval (CLTR). The total of the words in CLTR of all six trials is summed. The total score ranged from 0 to 72. Higher values represent a better outcome.

Outcome measures

Measure	Fingolimod n=80 Participants 0.5 mg in capsules for oral administration once daily	Interferon Beta 1b n=28 Participants 250 μg injected s.c. every other day
Change From Screening in Selective Reminding Test - Consistent Long Term Retrieval (SRT-CLTR) Raw Score	5.93 Raw score Standard Error 1.49	3.96 Raw score Standard Error 2.56

PRIMARY outcome

Timeframe: Screening (-1month), 18 month

Population: Full analysis set (FAS) - all randomized patients who received at least one dose of study drug and had at least one post-baseline assessment of both primary efficacy variables (i.e. non-missing information about the BRB and DKEFS - Sorting test) without any major protocol violations

Spatial Recall Test (SPART) for visuospatial learning and delayed recall.Spatial Recall Test (10/36): The spatial recall test assesses visuospatial learning and delayed recall (10/36-D). A checkerboard with ten checkers arranged in a pattern is shown to the subject for ten seconds. The subject is then asked to reproduce the same pattern with ten checkers on an empty checkerboard. The test includes three consecutive trials. The score is the total number of correct responses for the tree trials. The total score ranged from 0 to 30. Higher values represent a better outcome.

Outcome measures

Measure	Fingolimod n=80 Participants 0.5 mg in capsules for oral administration once daily	Interferon Beta 1b n=28 Participants 250 μg injected s.c. every other day
Change From Screening in Spatial Recall Test (SPART) Raw Score	1.46 Raw score Standard Error 0.52	3.06 Raw score Standard Error 0.89

PRIMARY outcome

Timeframe: Screening (-1month), 18 month

Population: Full analysis set (FAS) - all randomized patients who received at least one dose of study drug and had at least one post-baseline assessment of both primary efficacy variables (i.e. non-missing information about the BRB and DKEFS - Sorting test) without any major protocol violations

Symbol Digit Modality Test (SDMT) for sustained attention and information processing speed. It presents a series of nine symbols, each of which is paired with a single digit labeled 1-9 in a key at the top of the sheet. The reminder of the page has a pseudo-randomized sequence of symbols, and the patient must respond with the digit associated with each of these as quickly as possible. The score is the number of correct answers in 90 seconds. The total score ranged from 0 to 110. Higher values represent a better outcome.

Outcome measures

Measure	Fingolimod n=80 Participants 0.5 mg in capsules for oral administration once daily	Interferon Beta 1b n=28 Participants 250 μg injected s.c. every other day
Change From Screening in Symbol Digit Modalities Test (SDMT) Raw Score	2.19 Raw score Standard Error 1.12	3.93 Raw score Standard Error 1.93

PRIMARY outcome

Timeframe: Screening (-1month), 18 month

Population: Full analysis set (FAS) - all randomized patients who received at least one dose of study drug and had at least one post-baseline assessment of both primary efficacy variables (i.e. non-missing information about the BRB and DKEFS - Sorting test) without any major protocol violations

Paced Auditory Serial Addition Test (PASAT) for working memory (and sustained attention and information processing speed). The patient hears a series of numbers from recordings that are presented at the rate of one every 3 seconds in the first part of the test (PASAT-3). The patient is asked to add each consecutive digit to the one immediately preceding it. Sixty-one digits are presented for each part, and each part has a maximum of 60 correct answers. The total score ranged from 0 to 60. Higher values represent a better outcome.

Outcome measures

Measure	Fingolimod n=80 Participants 0.5 mg in capsules for oral administration once daily	Interferon Beta 1b n=28 Participants 250 μg injected s.c. every other day
Change From Screening in Paced Auditory Serial Addition Test - 3 Seconds (PASAT 3) Raw Score	7.14 Raw score Standard Error 1.24	6.68 Raw score Standard Error 2.13

PRIMARY outcome

Timeframe: Screening (-1month), 18 month

Population: Full analysis set (FAS) - all randomized patients who received at least one dose of study drug and had at least one post-baseline assessment of both primary efficacy variables (i.e. non-missing information about the BRB and DKEFS - Sorting test) without any major protocol violations

Paced Auditory Serial Addition Test (PASAT) for working memory (and sustained attention and information processing speed). The patient hears a series of numbers from recordings that are presented at the rate of one every 2 seconds in the second part of the test (PASAT-2). The patient was asked to add each consecutive digit to the one immediately preceding it. Sixty-one digits are presented for each part, and each part has a maximum of 60 correct answers. The total score ranged from 0 to 60. Higher values represent a better outcome.

Outcome measures

Measure	Fingolimod n=80 Participants 0.5 mg in capsules for oral administration once daily	Interferon Beta 1b n=28 Participants 250 μg injected s.c. every other day
Change From Screening in Paced Auditory Serial Addition Test - 2 (PASAT 2) Raw Score	4.79 Raw score Standard Error 1.25	4.42 Raw score Standard Error 2.14

PRIMARY outcome

Timeframe: Screening (-1month), 18 month

Population: Full analysis set (FAS) - all randomized patients who received at least one dose of study drug and had at least one post-baseline assessment of both primary efficacy variables (i.e. non-missing information about the BRB and DKEFS - Sorting test) without any major protocol violations

The tests SRT (Selective Reminding Test) for episodic memory (verbal learning and delayed recall). The Delayed SRT test is the total number of words recalled after a delayed period. The total score ranged from 0 to 12. Higher values represent a better outcome.

Outcome measures

Measure	Fingolimod n=80 Participants 0.5 mg in capsules for oral administration once daily	Interferon Beta 1b n=28 Participants 250 μg injected s.c. every other day
Change From Screening in Selective Reminding Test - Delayed Recall (SRT-D) Raw Score	0.57 Raw score Standard Error 0.23	0.39 Raw score Standard Error 0.40

PRIMARY outcome

Timeframe: Screening (-1month), 18 month

Population: Full analysis set (FAS) - all randomized patients who received at least one dose of study drug and had at least one post-baseline assessment of both primary efficacy variables (i.e. non-missing information about the BRB and DKEFS - Sorting test) without any major protocol violations

Spatial Recall Test (SPART) for visuospatial learning and delayed recall.Spatial Recall Test (10/36): The spatial recall test assesses visuospatial learning and delayed recall (10/36-D). A checkerboard with ten checkers arranged in a pattern was shown to the subject for ten seconds. The subject was then asked to reproduce the same pattern with ten checkers on an empty checkerboard. The test includes three consecutive trials. The score was the total number of correct responses for the tree trials. The total score ranged from 0 to 10. Higher values represent a better outcome.

Outcome measures

Measure	Fingolimod n=80 Participants 0.5 mg in capsules for oral administration once daily	Interferon Beta 1b n=28 Participants 250 μg injected s.c. every other day
Change From Screening in Spatial Recall Test - Delayed Recall (SPART-D)	0.41 Raw score Standard Error 0.21	0.44 Raw score Standard Error 0.36

PRIMARY outcome

Timeframe: Screening (-1month), 18 month

Population: Full analysis set (FAS) - all randomized patients who received at least one dose of study drug and had at least one post-baseline assessment of both primary efficacy variables (i.e. non-missing information about the BRB and DKEFS - Sorting test) without any major protocol violations

Word List Generation (COWAT/WLG): The COWAT assesses verbal fluency on semantic stimulus by asking the patient to produce as many words as possible belonging to a semantic category. The test assessed the verbal fluency, recorded all the possible correct word that a patients should give in 90 sec. No maximum range is available. Higher values represent a better outcome. The score was the number of correct words. The more words the patient pronounces, the better it is. We can imagine that the minimum value might be zero words, , but it is not a score scale.

Outcome measures

Measure	Fingolimod n=80 Participants 0.5 mg in capsules for oral administration once daily	Interferon Beta 1b n=28 Participants 250 μg injected s.c. every other day
Change From Screening in Word List Generation (WLG)	0.39 Raw score Standard Error 0.58	0.24 Raw score Standard Error 0.99

PRIMARY outcome

Timeframe: Screening (-1month), 18 month

Population: Full analysis set (FAS) - all randomized patients who received at least one dose of study drug and had at least one post-baseline assessment of both primary efficacy variables (i.e. non-missing information about the BRB and DKEFS - Sorting test) without any major protocol violations

The Delis-Kaplan Executive Function System - Sorting Test is one of the nine tests presented in the DKEFS manual and explores the patient's executive abilities. It has a standard form (version A, administered at screening and Month-18 visit) and an alternate form (version B, administered at Month-9 visit). The standard form consists of the practice card set, card set 1 and card set 2. The alternate form consists of the same practice card set, card set 3 and card set 4. The DKFES test consisted of two testing procedures: free sorting and sort recognition. In free sorting, six scores were obtained: Confirmed Correct sorts for card sets 1 and 2 (or 3 and 4 for version B), sum of confirmed Correct Sorts. In sort recognition, a description score for card set 1 and 2 (or 3 and 4 for version B) was obtained, as well as the sum of description scores of both sets. The total score ranged from 0 to 16. Higher values represent a better outcome

Outcome measures

Measure	Fingolimod n=80 Participants 0.5 mg in capsules for oral administration once daily	Interferon Beta 1b n=28 Participants 250 μg injected s.c. every other day
Change From Screening in Delis-Kaplan Executive Function System (DKEFS) Condition 1: Free Sorting, Confirmed Correct Sort- Card Set 1+2	0.57 Raw score Standard Error 0.31	0.82 Raw score Standard Error 0.48

PRIMARY outcome

Timeframe: Screening (-1month), 18 month

Population: Full analysis set (FAS) - all randomized patients who received at least one dose of study drug and had at least one post-baseline assessment of both primary efficacy variables (i.e. non-missing information about the BRB and DKEFS - Sorting test) without any major protocol violations

The Delis-Kaplan Executive Function System - Sorting Test is one of the nine tests presented in the DKEFS manual and explores the patient's executive abilities. It has a standard form (version A, administered at screening and Month-18 visit) and an alternate form (version B, administered at Month-9 visit). The standard form consists of the practice card set, card set 1 and card set 2. The alternate form consists of the same practice card set, card set 3 and card set 4. In free sorting, six scores were obtained: Confirmed Correct sorts for card sets 1 and 2 (or 3 and 4 for version B), sum of confirmed Correct Sorts, Free Sorting Description score for card set 1 and 2 (or 3 and 4 for version B) and sum of Free Sorting Description scores. In sort recognition, a description score for card set 1 and 2 (or 3 and 4 for version B) was obtained, as well as the sum of description scores of both sets. The total score ranged from 0 to 64. Higher values represent a better outcome

Outcome measures

Measure	Fingolimod n=80 Participants 0.5 mg in capsules for oral administration once daily	Interferon Beta 1b n=28 Participants 250 μg injected s.c. every other day
Change From Screening in DKEFS Condition 1: Free Sorting, Free Sorting, Description Score, Card Set 1+2	1.52 Raw score Standard Error 1.23	3.69 Raw score Standard Error 1.92

PRIMARY outcome

Timeframe: Screening (-1month), 18 month

Population: Full analysis set (FAS) - all randomized patients who received at least one dose of study drug and had at least one post-baseline assessment of both primary efficacy variables (i.e. non-missing information about the BRB and DKEFS - Sorting test) without any major protocol violations

The Delis-Kaplan Executive Function System - Sorting Test is one of the nine tests presented in the DKEFS manual and explores the patient's executive abilities. It has a standard form (version A, administered at screening and Month-18 visit) and an alternate form (version B, administered at Month-9 visit). The standard form consists of the practice card set, card set 1 and card set 2. The alternate form consists of the same practice card set, card set 3 and card set 4. Free sorting and sort recognition. In free sorting, six scores were obtained: Confirmed Correct sorts for card sets 1 and 2 (or 3 and 4 for version B), sum of confirmed Correct Sorts, Free Sorting Description score for card set 1 and 2 (or 3 and 4 for version B) and sum of Free Sorting Description scores. The total score ranged from 0 to 64. Higher values represent a better outcome.

Outcome measures

Measure	Fingolimod n=80 Participants 0.5 mg in capsules for oral administration once daily	Interferon Beta 1b n=28 Participants 250 μg injected s.c. every other day
Change From Screening in DKEFS Condition 2: Sort Recognition, Sort Recognition Description Score- Card Set 1+2	2.15 Raw score Standard Error 1.90	7.38 Raw score Standard Error 2.97

SECONDARY outcome

Timeframe: Screening (-1 month), 18 months

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

Outcome measures

Measure	Fingolimod n=68 Participants 0.5 mg in capsules for oral administration once daily	Interferon Beta 1b n=27 Participants 250 μg injected s.c. every other day
Change From Screening in the Volume of Total T2 Lesions	176.25 mm^3 Standard Deviation 1355.31	711.81 mm^3 Standard Deviation 1584.42

SECONDARY outcome

Timeframe: Screening (-1month), 18 month

Population: Full analysis set (FAS) - all randomized patients who received at least one dose of study drug and had at least one post-baseline assessment of both primary efficacy variables (i.e. non-missing information about the BRB and DKEFS - Sorting test) without any major protocol violations

MADRS measures the overall severity of depressive symptoms. The MADRS had a 10-item checklist. Items are rated on a scale of 0-6, for a total numeric range of scores from 0 (depressive symptoms absent) to 60 (numerically highest level of depressive symptoms).

Outcome measures

Measure	Fingolimod n=80 Participants 0.5 mg in capsules for oral administration once daily	Interferon Beta 1b n=28 Participants 250 μg injected s.c. every other day
Change From Screening in Montgomery-Asberg Depression Rating Scale (MADRS)	-0.77 Raw score Standard Error 0.79	0.13 Raw score Standard Error 1.31

SECONDARY outcome

Timeframe: Baseline, 18 months

Population: Full analysis set (FAS) - all randomized patients who received at least one dose of study drug and had at least one post-baseline assessment of both primary efficacy variables (i.e. non-missing information about the BRB and DKEFS - Sorting test) without any major protocol violations

A 54 question measure covers 12 domains; assesses mental and physical health. The physical health composite score is a weighted average of the physical health scales, such as physical function, health perceptions, and energy. The mental health composite score is a weighted average of the mental health scales, such as overall quality of life, cognitive function, and health distress. Each domain has a range from 0 to 100 where higher means better.

Outcome measures

Measure	Fingolimod n=80 Participants 0.5 mg in capsules for oral administration once daily	Interferon Beta 1b n=28 Participants 250 μg injected s.c. every other day
Changes in Quality of Life, by Means of the Multiple Sclerosis Quality of Life (MSQoL-54) Mental health composite score	4.76 Score Standard Error 2.01	-2.31 Score Standard Error 3.36
Changes in Quality of Life, by Means of the Multiple Sclerosis Quality of Life (MSQoL-54) Physical health composite score	-1.80 Score Standard Error 1.41	-4.75 Score Standard Error 2.46

SECONDARY outcome

Timeframe: Baseline, 18 months

Population: Full analysis set (FAS) - all randomized patients who received at least one dose of study drug and had at least one post-baseline assessment of both primary efficacy variables (i.e. non-missing information about the BRB and DKEFS - Sorting test) without any major protocol violations

Modified Fatigue Impact Scale (mFIS) questionnaire is described at each time point to evaluate fatigue by means of usual descriptive statistics. Three domains were also defined: Physical Subscale (sum of items 4, 6, 7, 10, 13, 14, 17, 20, 21 and therefore ranging from 0 to 36), Cognitive Subscale (sum of items 1, 2, 3, 5, 11, 12, 15, 16, 18, 19 and therefore ranging from 0 to 40) and Psychosocial Subscale (sum of items 8, 9 and therefore ranging from 0 to 8). Finally, mFIS - overall score ranged from 0 to 80. The mFIS total score was computed as the sum of scores for each item. Lower values represent a better outcome.

Outcome measures

Measure	Fingolimod n=80 Participants 0.5 mg in capsules for oral administration once daily	Interferon Beta 1b n=28 Participants 250 μg injected s.c. every other day
Changes From Baseline in Fatigue Impact Scale (mFIS, Total Score and Scores of the 3 Individual Domains).	2.36 Score Standard Error 1.68	6.67 Score Standard Error 2.72

SECONDARY outcome

Timeframe: Screening (-1month), 18 month

Population: Full analysis set (FAS) - all randomized patients who received at least one dose of study drug and had at least one post-baseline assessment of both primary efficacy variables (i.e. non-missing information about the BRB and DKEFS - Sorting test) without any major protocol violations

New T2 lesions at a specific visit were assessed relative to the previous visit scan. The total number of lesions (visit 8 to 18 month) is calculated as the sum of the number of lesions.

Outcome measures

Measure	Fingolimod n=80 Participants 0.5 mg in capsules for oral administration once daily	Interferon Beta 1b n=28 Participants 250 μg injected s.c. every other day
Change From Screening in the Number of New T2 Lesions	1.25 Number of new lesions Standard Deviation 2.05	3.33 Number of new lesions Standard Deviation 4.44

SECONDARY outcome

Timeframe: Screening (-1month), 18 month

Population: Full analysis set (FAS) - all randomized patients who received at least one dose of study drug and had at least one post-baseline assessment of both primary efficacy variables (i.e. non-missing information about the BRB and DKEFS - Sorting test) without any major protocol violations

Volume of hypointense post-gadolinium T1 lesion component was measured by MRI scan. Means were estimated using a Mixed-effect model with repeated measures (MMRM) by-visit interaction.

Outcome measures

Measure	Fingolimod n=80 Participants 0.5 mg in capsules for oral administration once daily	Interferon Beta 1b n=28 Participants 250 μg injected s.c. every other day
Change From Screening in the Volume of Total T1 Hypointense Lesions	391.96 mm^3 Standard Deviation 986.85	213.93 mm^3 Standard Deviation 312.24

SECONDARY outcome

Timeframe: Screening (-1month), 18 month

Population: Full analysis set (FAS) - all randomized patients who received at least one dose of study drug and had at least one post-baseline assessment of both primary efficacy variables (i.e. non-missing information about the BRB and DKEFS - Sorting test) without any major protocol violations

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	Fingolimod n=80 Participants 0.5 mg in capsules for oral administration once daily	Interferon Beta 1b n=28 Participants 250 μg injected s.c. every other day
Change From Screening in the Number of T1 Gd+ Enhancing Lesions	-0.64 Number of new lesions Standard Deviation 1.27	0.59 Number of new lesions Standard Deviation 3.98

SECONDARY outcome

Timeframe: Screening (-1month), 18 month

Population: Full analysis set (FAS) - all randomized patients who received at least one dose of study drug and had at least one post-baseline assessment of both primary efficacy variables (i.e. non-missing information about the BRB and DKEFS - Sorting test) without any major protocol violations

Calculations of brain volume change were performed using the structural image evaluation of normalized atrophy (SIENA), software included in the Functional Magnetic Resonance Imaging of the Brain (FMRIB) software library. SIENA is a fully automated method for estimating temporal brain volume change.

Outcome measures

Measure	Fingolimod n=80 Participants 0.5 mg in capsules for oral administration once daily	Interferon Beta 1b n=28 Participants 250 μg injected s.c. every other day
Change From Screening in the Percentage of Brain Volume Change	-0.60 percentage of brain volume Standard Deviation 0.83	-0.96 percentage of brain volume Standard Deviation 0.71

SECONDARY outcome

Timeframe: Baseline, 18 month

Population: Full analysis set (FAS) - all randomized patients who received at least one dose of study drug and had at least one post-baseline assessment of both primary efficacy variables (i.e. non-missing information about the BRB and DKEFS - Sorting test) without any major protocol violations

The Environmental Status Scale (ESS) is used to quickly evaluate a patient for handicap. It was derived from a measure of socio-economic status. It consists of seven parameters: (1) actual work status, (2) financial and economic status, (3) personal residence or home, (4) personal assistance required, (5) transportation, (6) community services, (7) social activity. Each parameter has a single score from minimum 0 to maximum 5. ESS score is the sum of the points for all 7 parameters: minimum score: 0; maximum score: 35. The higher the score the greater the handicap

Outcome measures

Measure	Fingolimod n=80 Participants 0.5 mg in capsules for oral administration once daily	Interferon Beta 1b n=28 Participants 250 μg injected s.c. every other day
Changes in the Environmental Status Scale Score (ESS)	1.08 Score Standard Deviation 3.45	0.91 Score Standard Deviation 1.98

Adverse Events

Fingolimod 0.5 mg

Serious events: 9 serious events

Other events: 44 other events

Deaths: 0 deaths

Interferon Beta 1b

Serious events: 1 serious events

Other events: 22 other events

Deaths: 0 deaths

Serious adverse events

Measure	Fingolimod 0.5 mg n=104 participants at risk 0.5 mg in capsules for oral administration once daily	Interferon Beta 1b n=47 participants at risk 250 μg injected s.c. every other day
Cardiac disorders Atrioventricular block second degree	0.96% 1/104	0.00% 0/47
Infections and infestations Bronchopneumonia	0.96% 1/104	0.00% 0/47
Infections and infestations Urinary tract infection	0.96% 1/104	0.00% 0/47
Injury, poisoning and procedural complications Facial bones fracture	0.96% 1/104	0.00% 0/47
Injury, poisoning and procedural complications Head injury	0.96% 1/104	0.00% 0/47
Injury, poisoning and procedural complications Traumatic brain injury	0.96% 1/104	0.00% 0/47
Injury, poisoning and procedural complications Ulna fracture	0.96% 1/104	0.00% 0/47
Investigations Blood glucose abnormal	0.00% 0/104	2.1% 1/47
Nervous system disorders Epilepsy	0.96% 1/104	0.00% 0/47
Renal and urinary disorders Nephrolithiasis	0.96% 1/104	0.00% 0/47
Renal and urinary disorders Renal colic	1.9% 2/104	0.00% 0/47
Surgical and medical procedures Uterine polypectomy	0.96% 1/104	0.00% 0/47

Other adverse events

Measure	Fingolimod 0.5 mg n=104 participants at risk 0.5 mg in capsules for oral administration once daily	Interferon Beta 1b n=47 participants at risk 250 μg injected s.c. every other day
General disorders Influenza like illness	0.96% 1/104	10.6% 5/47
General disorders Pyrexia	5.8% 6/104	8.5% 4/47
Infections and infestations Nasopharyngitis	3.8% 4/104	6.4% 3/47
Investigations Alanine aminotransferase increased	8.7% 9/104	2.1% 1/47
Investigations Blood triglycerides increased	0.00% 0/104	6.4% 3/47
Investigations Transaminases increased	3.8% 4/104	8.5% 4/47
Metabolism and nutrition disorders Hypercholesterolaemia	6.7% 7/104	4.3% 2/47
Musculoskeletal and connective tissue disorders Back pain	2.9% 3/104	6.4% 3/47
Nervous system disorders Headache	10.6% 11/104	8.5% 4/47
Nervous system disorders Multiple sclerosis relapse	1.9% 2/104	8.5% 4/47
Psychiatric disorders Depression	6.7% 7/104	6.4% 3/47

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 or disclosure of trial results in their entirety.
• Publication restrictions are in place

Restriction type: OTHER