Trial Outcomes & Findings for Efficacy and Safety of Fingolimod in Patients With Relapsing-remitting Multiple Sclerosis (NCT NCT00289978)

Last Updated: 2012-04-11

Results Overview

The ARR is defined as the number of confirmed relapses in a year. A relapse is defined as the appearance of a new or worsening of a previously stable or improving pre-existing neurological abnormality, separated by at least 30 days from onset of a preceding relapse. The abnormality must be present for at least 24 hours and occur in the absence of fever or infection. The annualized ARR for each treatment group was the mean of the annualized ARRs for all patients in the group calculated as the total number of confirmed relapses divided by the total number of days on study, multiplied by 365.25.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1272 participants

Primary outcome timeframe

Baseline to end of study (Month 24)

Results posted on

2012-04-11

Participant Flow

Participant milestones

Participant milestones
Measure	Fingolimod 1.25 mg Patients self-administered fingolimod 1.25 mg capsules orally once daily.	Fingolimod 0.5 mg Patients self-administered fingolimod 0.5 mg capsules orally once daily.	Placebo Patients self-administered a fingolimod placebo capsule orally once daily.
Overall Study STARTED	429	425	418
Overall Study COMPLETED	332	369	332
Overall Study NOT COMPLETED	97	56	86

Reasons for withdrawal

Reasons for withdrawal
Measure	Fingolimod 1.25 mg Patients self-administered fingolimod 1.25 mg capsules orally once daily.	Fingolimod 0.5 mg Patients self-administered fingolimod 0.5 mg capsules orally once daily.	Placebo Patients self-administered a fingolimod placebo capsule orally once daily.
Overall Study Withdrawal by Subject	31	17	28
Overall Study Adverse Event	22	13	18
Overall Study Lack of Efficacy	13	6	25
Overall Study Abnormal laboratory value(s)	20	9	1
Overall Study Lost to Follow-up	3	5	7
Overall Study Protocol Violation	5	5	4
Overall Study Abnormal test procedure result(s)	2	1	1
Overall Study Death	1	0	2

Baseline Characteristics

Efficacy and Safety of Fingolimod in Patients With Relapsing-remitting Multiple Sclerosis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Fingolimod 1.25 mg n=429 Participants Patients self-administered fingolimod 1.25 mg capsules orally once daily.	Fingolimod 0.5 mg n=425 Participants Patients self-administered fingolimod 0.5 mg capsules orally once daily.	Placebo n=418 Participants Patients self-administered a fingolimod placebo capsule orally once daily.	Total n=1272 Participants Total of all reporting groups
Age Continuous	37.4 years STANDARD_DEVIATION 8.91 • n=5 Participants	36.6 years STANDARD_DEVIATION 8.77 • n=7 Participants	37.2 years STANDARD_DEVIATION 8.60 • n=5 Participants	37.1 years STANDARD_DEVIATION 8.76 • n=4 Participants
Age, Customized <18 years	1 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	1 participants n=4 Participants
Age, Customized 18 -30	107 participants n=5 Participants	120 participants n=7 Participants	97 participants n=5 Participants	324 participants n=4 Participants
Age, Customized 31-40	147 participants n=5 Participants	162 participants n=7 Participants	165 participants n=5 Participants	474 participants n=4 Participants
Age, Customized 41-55	174 participants n=5 Participants	143 participants n=7 Participants	156 participants n=5 Participants	473 participants n=4 Participants
Sex: Female, Male Female	295 Participants n=5 Participants	296 Participants n=7 Participants	298 Participants n=5 Participants	889 Participants n=4 Participants
Sex: Female, Male Male	134 Participants n=5 Participants	129 Participants n=7 Participants	120 Participants n=5 Participants	383 Participants n=4 Participants
Duration of multiple sclerosis since first symptoms	8.4 Years STANDARD_DEVIATION 6.86 • n=5 Participants	8.0 Years STANDARD_DEVIATION 6.60 • n=7 Participants	8.1 Years STANDARD_DEVIATION 6.35 • n=5 Participants	8.2 Years STANDARD_DEVIATION 6.60 • n=4 Participants
Number of relapses in last 2 years	1.5 relapses STANDARD_DEVIATION 0.81 • n=5 Participants	1.5 relapses STANDARD_DEVIATION 0.76 • n=7 Participants	1.4 relapses STANDARD_DEVIATION 0.73 • n=5 Participants	1.5 relapses STANDARD_DEVIATION 0.77 • n=4 Participants
Expanded Disability Status Scale (EDSS)	2.41 Units on a scale STANDARD_DEVIATION 1.36 • n=5 Participants	2.30 Units on a scale STANDARD_DEVIATION 1.29 • n=7 Participants	2.49 Units on a scale STANDARD_DEVIATION 1.29 • n=5 Participants	2.40 Units on a scale STANDARD_DEVIATION 1.32 • n=4 Participants

PRIMARY outcome

Timeframe: Baseline to end of study (Month 24)

Population: This analysis was conducted using the Intent-to-treat (ITT) population which includes all patients who were randomized and received at least one dose of study drug.

Outcome measures

Outcome measures
Measure	Fingolimod 1.25 mg n=429 Participants Patients self-administered fingolimod 1.25 mg capsules orally once daily.	Fingolimod 0.5 mg n=425 Participants Patients self-administered fingolimod 0.5 mg capsules orally once daily.	Placebo n=418 Participants Patients self-administered a fingolimod placebo capsule orally once daily.
Estimated Annualized Aggregate Relapse Rate (ARR)	0.16 Relapses per year Interval 0.13 to 0.19	0.18 Relapses per year Interval 0.15 to 0.22	0.40 Relapses per year Interval 0.34 to 0.47

SECONDARY outcome

Timeframe: Baseline to end of study (Month 24)

Population: Intent-to-treat population (ITT): All patients who were randomized and received at least one dose of study medication.

EDSS assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to MS) is calculated. Disability progression was determined by the following: 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. A 3-month confirmed disability progression required onset EDSS, 3-month confirming EDSS, and all EDSS in between to meet the disability progression criteria. Percent of free of disability progression was calculated using the Kaplan Meier method.

Outcome measures

Outcome measures
Measure	Fingolimod 1.25 mg n=429 Participants Patients self-administered fingolimod 1.25 mg capsules orally once daily.	Fingolimod 0.5 mg n=425 Participants Patients self-administered fingolimod 0.5 mg capsules orally once daily.	Placebo n=418 Participants Patients self-administered a fingolimod placebo capsule orally once daily.
Percentage of Patients Free of Disability Progression at Month 24 Assessed With the Expanded Disability Status Scale (EDSS)	83.4 Percentage of participants 95% Confidence Interval 1.87 • Interval 79.7 to 87.1	82.3 Percentage of participants 95% Confidence Interval 1.89 • Interval 78.6 to 86.1	75.9 Percentage of participants 95% Confidence Interval 2.17 • Interval 71.7 to 80.2

SECONDARY outcome

Timeframe: Baseline to end of study (Month 24)

Population: Intent-to-treat population (ITT): All patients who were randomized and received at least one dose of study medication.

The number of new or newly enlarged T2 lesions at Month 24 in comparison to baseline was assessed with T2-weighted magnetic resonance image (MRI) scans. A T2-weighted MRI scan utilizes particular values of the echo time (TE) and the repetition time (TR) parameters of image acquisition. Inflammation and tissue damage are seen as bright areas in T2 images and are often referred to as T2 lesions. T2-weighted MRI scans are a sensitive way to evaluate the brain for demyelinating diseases, such as multiple sclerosis.

Outcome measures

Outcome measures
Measure	Fingolimod 1.25 mg n=337 patients with non-missing values Patients self-administered fingolimod 1.25 mg capsules orally once daily.	Fingolimod 0.5 mg n=370 patients with non-missing values Patients self-administered fingolimod 0.5 mg capsules orally once daily.	Placebo n=339 patients with non-missing values Patients self-administered a fingolimod placebo capsule orally once daily.
Number of New or Newly Enlarged T2 Lesions at Month 24 in Comparison With Baseline	2.5 T2 lesions Standard Deviation 5.52	2.5 T2 lesions Standard Deviation 7.19	9.8 T2 lesions Standard Deviation 13.17

Adverse Events

Fingolimod 1.25 mg

Serious events: 51 serious events

Other events: 346 other events

Deaths: 0 deaths

Fingolimod 0.5 mg

Serious events: 43 serious events

Other events: 355 other events

Deaths: 0 deaths

Placebo

Serious events: 56 serious events

Other events: 323 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

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

Measure	Fingolimod 1.25 mg n=429 participants at risk Patients self-administered fingolimod 1.25 mg capsules orally once daily.	Fingolimod 0.5 mg n=425 participants at risk Patients self-administered fingolimod 0.5 mg capsules orally once daily.	Placebo n=418 participants at risk Patients self-administered a fingolimod placebo capsule orally once daily.
Ear and labyrinth disorders Vertigo	4.2% 18/429 • 24 Months Adverse events are reported based on the safety population. The safety population consists of all patients who received at least 1 dose of study drug.	4.2% 18/425 • 24 Months Adverse events are reported based on the safety population. The safety population consists of all patients who received at least 1 dose of study drug.	5.0% 21/418 • 24 Months Adverse events are reported based on the safety population. The safety population consists of all patients who received at least 1 dose of study drug.
Gastrointestinal disorders Diarrhoea	9.3% 40/429 • 24 Months Adverse events are reported based on the safety population. The safety population consists of all patients who received at least 1 dose of study drug.	11.8% 50/425 • 24 Months Adverse events are reported based on the safety population. The safety population consists of all patients who received at least 1 dose of study drug.	7.2% 30/418 • 24 Months Adverse events are reported based on the safety population. The safety population consists of all patients who received at least 1 dose of study drug.
Gastrointestinal disorders Nausea	8.9% 38/429 • 24 Months Adverse events are reported based on the safety population. The safety population consists of all patients who received at least 1 dose of study drug.	8.9% 38/425 • 24 Months Adverse events are reported based on the safety population. The safety population consists of all patients who received at least 1 dose of study drug.	8.6% 36/418 • 24 Months Adverse events are reported based on the safety population. The safety population consists of all patients who received at least 1 dose of study drug.
General disorders Fatigue	10.7% 46/429 • 24 Months Adverse events are reported based on the safety population. The safety population consists of all patients who received at least 1 dose of study drug.	11.3% 48/425 • 24 Months Adverse events are reported based on the safety population. The safety population consists of all patients who received at least 1 dose of study drug.	10.8% 45/418 • 24 Months Adverse events are reported based on the safety population. The safety population consists of all patients who received at least 1 dose of study drug.
Infections and infestations Bronchitis	9.1% 39/429 • 24 Months Adverse events are reported based on the safety population. The safety population consists of all patients who received at least 1 dose of study drug.	8.0% 34/425 • 24 Months Adverse events are reported based on the safety population. The safety population consists of all patients who received at least 1 dose of study drug.	3.6% 15/418 • 24 Months Adverse events are reported based on the safety population. The safety population consists of all patients who received at least 1 dose of study drug.
Infections and infestations Influenza	9.3% 40/429 • 24 Months Adverse events are reported based on the safety population. The safety population consists of all patients who received at least 1 dose of study drug.	12.9% 55/425 • 24 Months Adverse events are reported based on the safety population. The safety population consists of all patients who received at least 1 dose of study drug.	9.8% 41/418 • 24 Months Adverse events are reported based on the safety population. The safety population consists of all patients who received at least 1 dose of study drug.
Infections and infestations Nasopharyngitis	26.1% 112/429 • 24 Months Adverse events are reported based on the safety population. The safety population consists of all patients who received at least 1 dose of study drug.	27.1% 115/425 • 24 Months Adverse events are reported based on the safety population. The safety population consists of all patients who received at least 1 dose of study drug.	27.5% 115/418 • 24 Months Adverse events are reported based on the safety population. The safety population consists of all patients who received at least 1 dose of study drug.
Infections and infestations Pharyngitis	5.8% 25/429 • 24 Months Adverse events are reported based on the safety population. The safety population consists of all patients who received at least 1 dose of study drug.	6.1% 26/425 • 24 Months Adverse events are reported based on the safety population. The safety population consists of all patients who received at least 1 dose of study drug.	5.5% 23/418 • 24 Months Adverse events are reported based on the safety population. The safety population consists of all patients who received at least 1 dose of study drug.
Infections and infestations Rhinitis	4.2% 18/429 • 24 Months Adverse events are reported based on the safety population. The safety population consists of all patients who received at least 1 dose of study drug.	5.9% 25/425 • 24 Months Adverse events are reported based on the safety population. The safety population consists of all patients who received at least 1 dose of study drug.	6.0% 25/418 • 24 Months Adverse events are reported based on the safety population. The safety population consists of all patients who received at least 1 dose of study drug.
Infections and infestations Sinusitis	6.3% 27/429 • 24 Months Adverse events are reported based on the safety population. The safety population consists of all patients who received at least 1 dose of study drug.	6.4% 27/425 • 24 Months Adverse events are reported based on the safety population. The safety population consists of all patients who received at least 1 dose of study drug.	4.5% 19/418 • 24 Months Adverse events are reported based on the safety population. The safety population consists of all patients who received at least 1 dose of study drug.
Infections and infestations Upper respiratory tract infection	14.5% 62/429 • 24 Months Adverse events are reported based on the safety population. The safety population consists of all patients who received at least 1 dose of study drug.	17.2% 73/425 • 24 Months Adverse events are reported based on the safety population. The safety population consists of all patients who received at least 1 dose of study drug.	17.2% 72/418 • 24 Months Adverse events are reported based on the safety population. The safety population consists of all patients who received at least 1 dose of study drug.
Infections and infestations Urinary tract infection	4.9% 21/429 • 24 Months Adverse events are reported based on the safety population. The safety population consists of all patients who received at least 1 dose of study drug.	8.0% 34/425 • 24 Months Adverse events are reported based on the safety population. The safety population consists of all patients who received at least 1 dose of study drug.	11.2% 47/418 • 24 Months Adverse events are reported based on the safety population. The safety population consists of all patients who received at least 1 dose of study drug.
Investigations Alanine aminotransferase increased	11.4% 49/429 • 24 Months Adverse events are reported based on the safety population. The safety population consists of all patients who received at least 1 dose of study drug.	9.9% 42/425 • 24 Months Adverse events are reported based on the safety population. The safety population consists of all patients who received at least 1 dose of study drug.	3.8% 16/418 • 24 Months Adverse events are reported based on the safety population. The safety population consists of all patients who received at least 1 dose of study drug.
Investigations Gamma-glutamyltransferase increased	7.2% 31/429 • 24 Months Adverse events are reported based on the safety population. The safety population consists of all patients who received at least 1 dose of study drug.	5.2% 22/425 • 24 Months Adverse events are reported based on the safety population. The safety population consists of all patients who received at least 1 dose of study drug.	0.96% 4/418 • 24 Months Adverse events are reported based on the safety population. The safety population consists of all patients who received at least 1 dose of study drug.
Investigations Weight increased	3.3% 14/429 • 24 Months Adverse events are reported based on the safety population. The safety population consists of all patients who received at least 1 dose of study drug.	3.3% 14/425 • 24 Months Adverse events are reported based on the safety population. The safety population consists of all patients who received at least 1 dose of study drug.	5.3% 22/418 • 24 Months Adverse events are reported based on the safety population. The safety population consists of all patients who received at least 1 dose of study drug.
Metabolism and nutrition disorders Hypercholesterolaemia	6.1% 26/429 • 24 Months Adverse events are reported based on the safety population. The safety population consists of all patients who received at least 1 dose of study drug.	5.6% 24/425 • 24 Months Adverse events are reported based on the safety population. The safety population consists of all patients who received at least 1 dose of study drug.	6.2% 26/418 • 24 Months Adverse events are reported based on the safety population. The safety population consists of all patients who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Arthralgia	6.1% 26/429 • 24 Months Adverse events are reported based on the safety population. The safety population consists of all patients who received at least 1 dose of study drug.	7.1% 30/425 • 24 Months Adverse events are reported based on the safety population. The safety population consists of all patients who received at least 1 dose of study drug.	7.9% 33/418 • 24 Months Adverse events are reported based on the safety population. The safety population consists of all patients who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Back pain	10.5% 45/429 • 24 Months Adverse events are reported based on the safety population. The safety population consists of all patients who received at least 1 dose of study drug.	11.5% 49/425 • 24 Months Adverse events are reported based on the safety population. The safety population consists of all patients who received at least 1 dose of study drug.	6.7% 28/418 • 24 Months Adverse events are reported based on the safety population. The safety population consists of all patients who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Pain in extremity	5.6% 24/429 • 24 Months Adverse events are reported based on the safety population. The safety population consists of all patients who received at least 1 dose of study drug.	6.6% 28/425 • 24 Months Adverse events are reported based on the safety population. The safety population consists of all patients who received at least 1 dose of study drug.	6.5% 27/418 • 24 Months Adverse events are reported based on the safety population. The safety population consists of all patients who received at least 1 dose of study drug.
Nervous system disorders Dizziness	7.2% 31/429 • 24 Months Adverse events are reported based on the safety population. The safety population consists of all patients who received at least 1 dose of study drug.	7.3% 31/425 • 24 Months Adverse events are reported based on the safety population. The safety population consists of all patients who received at least 1 dose of study drug.	5.5% 23/418 • 24 Months Adverse events are reported based on the safety population. The safety population consists of all patients who received at least 1 dose of study drug.
Nervous system disorders Headache	26.3% 113/429 • 24 Months Adverse events are reported based on the safety population. The safety population consists of all patients who received at least 1 dose of study drug.	25.2% 107/425 • 24 Months Adverse events are reported based on the safety population. The safety population consists of all patients who received at least 1 dose of study drug.	23.0% 96/418 • 24 Months Adverse events are reported based on the safety population. The safety population consists of all patients who received at least 1 dose of study drug.
Nervous system disorders Paraesthesia	4.0% 17/429 • 24 Months Adverse events are reported based on the safety population. The safety population consists of all patients who received at least 1 dose of study drug.	5.4% 23/425 • 24 Months Adverse events are reported based on the safety population. The safety population consists of all patients who received at least 1 dose of study drug.	4.3% 18/418 • 24 Months Adverse events are reported based on the safety population. The safety population consists of all patients who received at least 1 dose of study drug.
Psychiatric disorders Depression	5.8% 25/429 • 24 Months Adverse events are reported based on the safety population. The safety population consists of all patients who received at least 1 dose of study drug.	7.8% 33/425 • 24 Months Adverse events are reported based on the safety population. The safety population consists of all patients who received at least 1 dose of study drug.	6.7% 28/418 • 24 Months Adverse events are reported based on the safety population. The safety population consists of all patients who received at least 1 dose of study drug.
Psychiatric disorders Insomnia	3.7% 16/429 • 24 Months Adverse events are reported based on the safety population. The safety population consists of all patients who received at least 1 dose of study drug.	4.9% 21/425 • 24 Months Adverse events are reported based on the safety population. The safety population consists of all patients who received at least 1 dose of study drug.	6.0% 25/418 • 24 Months Adverse events are reported based on the safety population. The safety population consists of all patients who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Cough	8.6% 37/429 • 24 Months Adverse events are reported based on the safety population. The safety population consists of all patients who received at least 1 dose of study drug.	10.1% 43/425 • 24 Months Adverse events are reported based on the safety population. The safety population consists of all patients who received at least 1 dose of study drug.	8.1% 34/418 • 24 Months Adverse events are reported based on the safety population. The safety population consists of all patients who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Dyspnoea	5.8% 25/429 • 24 Months Adverse events are reported based on the safety population. The safety population consists of all patients who received at least 1 dose of study drug.	7.1% 30/425 • 24 Months Adverse events are reported based on the safety population. The safety population consists of all patients who received at least 1 dose of study drug.	4.5% 19/418 • 24 Months Adverse events are reported based on the safety population. The safety population consists of all patients who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	4.0% 17/429 • 24 Months Adverse events are reported based on the safety population. The safety population consists of all patients who received at least 1 dose of study drug.	6.8% 29/425 • 24 Months Adverse events are reported based on the safety population. The safety population consists of all patients who received at least 1 dose of study drug.	6.9% 29/418 • 24 Months Adverse events are reported based on the safety population. The safety population consists of all patients who received at least 1 dose of study drug.
Vascular disorders Hypertension	6.3% 27/429 • 24 Months Adverse events are reported based on the safety population. The safety population consists of all patients who received at least 1 dose of study drug.	6.1% 26/425 • 24 Months Adverse events are reported based on the safety population. The safety population consists of all patients who received at least 1 dose of study drug.	3.6% 15/418 • 24 Months Adverse events are reported based on the safety population. The safety population consists of all patients who received at least 1 dose of study drug.