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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00662649




Registration number
NCT00662649
Ethics application status
Date submitted
17/04/2008
Date registered
21/04/2008
Date last updated
12/07/2012

Titles & IDs
Public title
Long-term Efficacy and Safety of Fingolimod (FTY720) in Patients With Relapsing-remitting Multiple Sclerosis
Scientific title
An Extension of the 24-month, Double-blind, Randomized, Multicenter, Placebo-controlled, Parallel-group Study Comparing Efficacy and Safety of Fingolimod (FTY720) 1.25 mg and 0.5 mg Administered Orally Once Daily Versus Placebo in Patients With Relapsing-remitting Multiple Sclerosis
Secondary ID [1] 0 0
2007-004122-24
Secondary ID [2] 0 0
CFTY720D2301E1
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Multiple Sclerosis 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Fingolimod 0.5 mg
Treatment: Drugs - Fingolimod 1.25 mg

Experimental: Fingolimod 1.25 mg - Patients continued the same dose to which they had been randomized in the Core study (CFTY720D2301/NCT00289978), fingolimod 1.25 mg/day, in this Extension study.

Experimental: Fingolimod 0.5 mg - Patients continued the same dose to which they had been randomized in the Core study, fingolimod 0.5 mg/day, in this Extension study.

Experimental: Placebo-fingolimod - Patients randomized to placebo in the Core study were re randomized to fingolimod (either 0.5 or 1.25 mg/day) in this Extension study.

Experimental: Placebo-fingolimod 1.25 mg - Patients randomized to placebo in the Core study were re randomized to fingolimod 1.25 mg/day in this Extension study.

Experimental: Placebo-fingolimod 0.5 mg - Patients randomized to placebo in the Core study were re randomized to fingolimod 0.5 mg/day in this Extension study.


Treatment: Drugs: Fingolimod 0.5 mg
Patients self-administered fingolimod 0.5 mg capsules orally once daily.

Treatment: Drugs: Fingolimod 1.25 mg
Patients self-administered fingolimod 1.25 mg capsules orally once daily.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Annualized Aggregate Relapse Rate (ARR) During Months 0 to End of Study(Core [CFTY720D2301/NCT00289978] and Extension Study) - 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.
Timepoint [1] 0 0
Months 0 to end of study (maximum up to 60 months)
Primary outcome [2] 0 0
Time to First Confirmed Relapse up to End of Study: Kaplan-Meier Estimate of Percentage of Patients Relapse-free - A relapse was confirmed when it was accompanied by an increase of at least half a step (0.5) on the Expanded Disability Status Scale (EDSS) or an increase of 1 point on two different Functional Systems (FS) of the EDSS or 2 points on one of the FS (excluding Bowel/Bladder or Cerebral FS). Kaplan-Meier estimates of the percentage of relapse-free patients at end of study and and 95% confidence intervals (CIs) were presented for the treatment groups.
Timepoint [2] 0 0
Core baseline to end of study (maximum up to 60 months)
Primary outcome [3] 0 0
Annualized Aggregate Relapse Rate (ARR) During Months 0-24 (Core Study) and Months 24-48 (Extension Study) - 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.
Timepoint [3] 0 0
Months 0-24 (core study) and Months 24-48 (extension study)
Primary outcome [4] 0 0
Change (Expressed as Ratio) in the Annualized Aggregate Relapse Rate (ARR) From Months 0-24 (Core Study) to Months 24-48 (Extension Study) - 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.
Timepoint [4] 0 0
Months 0-24 (core study) and Months 24-48 (extension study)
Secondary outcome [1] 0 0
Change in Mean Number of New or Newly Enlarged T2 Magnetic Resonance Imaging (MRI) Lesions During Months 0-24 (Core Study) and Months 24-48 (Extension Study) - The number of new or newly enlarged T2 lesions was assessed with T2-weighted 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.
Timepoint [1] 0 0
Months 0-24 (core study) and Months 24-48 (extension study)
Secondary outcome [2] 0 0
Percentage of Patients Free of New or Newly Enlarged T2 Magnetic Resonance Imaging (MRI) Lesions During Months 0-24 (Core Study) and Months 24-48 (Extension Study) - The number of new or newly enlarged T2 lesions was assessed with T2-weighted 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.
Timepoint [2] 0 0
Months 0-24 (core study) and Months 24-48 (extension study)
Secondary outcome [3] 0 0
Percent Change in Brain Volume From Month 0 to Month 24 (Core Study) and From Month 24 to Month 48 (Extension Study) - 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.
Timepoint [3] 0 0
Months 0-24 (core study) and Months 24-48 (extension study)
Secondary outcome [4] 0 0
Percent Change in Brain Volume From Month 0 End of Study (Core and Extension Study) - 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.
Timepoint [4] 0 0
Months 0 to end of study (maximum up to 60 months)
Secondary outcome [5] 0 0
Time to First 3-month Confirmed Disability Progression up to End of Study Based on Expanded Disability Status Scale (EDSS): Kaplan-Meier Estimate of Percentage of Patients Free of Disability Progression - Kurtzke's Expanded Disability Status Scale (EDSS) is a scale for assessing neurologic impairment in multiple sclerosis (MS) includes a series of scores in each of eight functional systems such as Visual, Brain Stem, Pyramidal, Cerebellar, Sensory, Bowel & Bladder, Cerebral, and Other. The EDSS steps range from 0 (normal) to 10 (death due to MS). The Kaplan-Meier estimates of the percentage of participants free of disability progression at end of study and their 95% CIs were provided for each treatment group.
Timepoint [5] 0 0
Core baseline to end of study (maximum up to 60 months)

Eligibility
Key inclusion criteria
- Patients should complete the 24 month core study
Minimum age
20 Years
Maximum age
58 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Patients with other chronic disease of the immune system, malignancies, acute
pulmonary disease, cardiac failure, etc.

- Pregnant or nursing women

Other protocol-defined inclusion/exclusion criteria may apply.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Novartis Investigative Site - Chatswood
Recruitment hospital [2] 0 0
Novartis Investigative Site - Fitzroy
Recruitment hospital [3] 0 0
Austin Health, Department of Neurology - Heidelberg
Recruitment hospital [4] 0 0
Novartis Investigative Site - North Gosford
Recruitment hospital [5] 0 0
Novartis Investigative Site - Woodville
Recruitment postcode(s) [1] 0 0
- Chatswood
Recruitment postcode(s) [2] 0 0
3065 - Fitzroy
Recruitment postcode(s) [3] 0 0
- Heidelberg
Recruitment postcode(s) [4] 0 0
- North Gosford
Recruitment postcode(s) [5] 0 0
- Woodville
Recruitment outside Australia
Country [1] 0 0
Belgium
State/province [1] 0 0
Brugge
Country [2] 0 0
Belgium
State/province [2] 0 0
Bruxelles
Country [3] 0 0
Belgium
State/province [3] 0 0
Charleroi
Country [4] 0 0
Belgium
State/province [4] 0 0
Leuven
Country [5] 0 0
Belgium
State/province [5] 0 0
Overpelt
Country [6] 0 0
Belgium
State/province [6] 0 0
Sijsele - Damme
Country [7] 0 0
Belgium
State/province [7] 0 0
Sint-Truiden
Country [8] 0 0
Canada
State/province [8] 0 0
Halifax
Country [9] 0 0
Canada
State/province [9] 0 0
Kingston
Country [10] 0 0
Canada
State/province [10] 0 0
London
Country [11] 0 0
Canada
State/province [11] 0 0
Montreal
Country [12] 0 0
Canada
State/province [12] 0 0
Nepean
Country [13] 0 0
Canada
State/province [13] 0 0
Regina
Country [14] 0 0
Canada
State/province [14] 0 0
Toronto
Country [15] 0 0
Canada
State/province [15] 0 0
Vancouver
Country [16] 0 0
Czech Republic
State/province [16] 0 0
Brno
Country [17] 0 0
Czech Republic
State/province [17] 0 0
Olomouc
Country [18] 0 0
Czech Republic
State/province [18] 0 0
Ostrava-Poruba
Country [19] 0 0
Czech Republic
State/province [19] 0 0
Pardubice
Country [20] 0 0
Czech Republic
State/province [20] 0 0
Plzen - Lochotin
Country [21] 0 0
Czech Republic
State/province [21] 0 0
Prague 5
Country [22] 0 0
Czech Republic
State/province [22] 0 0
Praha 2
Country [23] 0 0
Czech Republic
State/province [23] 0 0
Rychnov nad Kneznou
Country [24] 0 0
Czech Republic
State/province [24] 0 0
Teplice
Country [25] 0 0
Estonia
State/province [25] 0 0
Talinn
Country [26] 0 0
Finland
State/province [26] 0 0
Helsinki
Country [27] 0 0
Finland
State/province [27] 0 0
Tampere
Country [28] 0 0
Finland
State/province [28] 0 0
Turku
Country [29] 0 0
France
State/province [29] 0 0
Clermont Ferrand Cedex
Country [30] 0 0
France
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Dijon
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France
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Lille Cedex
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France
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Marseille cedex 05
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France
State/province [33] 0 0
Montpellier cedex 5
Country [34] 0 0
France
State/province [34] 0 0
Nantes
Country [35] 0 0
France
State/province [35] 0 0
Paris Cedex 13
Country [36] 0 0
France
State/province [36] 0 0
Rennes
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France
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Strasbourg
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Germany
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Berlin
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Duesseldorf
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Gießen
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Hamburg
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Leipzig
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Magdeburg
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Germany
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Muenchen
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Germany
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Muenster
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Germany
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Regensburg
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Germany
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Stuttgart
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Germany
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Tübingen
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Greece
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Athens
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Hungary
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Budapest
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Hungary
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Miskolc
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Hungary
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Szekesfehervar
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Ireland
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Dublin 4
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Israel
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Ashkelon
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Israel
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Haifa
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Israel
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Ramat Gan
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Israel
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Safed
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Netherlands
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Amsterdam
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Nieuwegein
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Nijmegen
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Rotterdam
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Sittard
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Tilburg
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Bialystok
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Gdansk
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Katowice
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Lodz
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Poznan
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Warsaw
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Warszawa
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Romania
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Bucharest
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Romania
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Craiova
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Romania
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Lasi
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Romania
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Tg. Mures
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Russian Federation
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Kazan
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Russian Federation
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Moscow
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Russian Federation
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St. Petersburg
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Slovakia
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Bratislava
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Slovakia
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Martin
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Slovakia
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Zilina
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South Africa
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Cape Town
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South Africa
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Rosebank
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South Africa
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Umhlanga
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Sweden
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Göteborg
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Sweden
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Stockholm
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Switzerland
State/province [86] 0 0
Lausanne
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Switzerland
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Zuerich
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Turkey
State/province [88] 0 0
Ankara
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Turkey
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Bursa
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Turkey
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Cerrahpasa/Istanbul
Country [91] 0 0
Turkey
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Gaziantep
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Turkey
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Istanbul
Country [93] 0 0
Turkey
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Izmir
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Turkey
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Mersin
Country [95] 0 0
Turkey
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Yenisehir/Izmir
Country [96] 0 0
United Kingdom
State/province [96] 0 0
Bristol
Country [97] 0 0
United Kingdom
State/province [97] 0 0
London
Country [98] 0 0
United Kingdom
State/province [98] 0 0
Newcastle Upon Tyne
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United Kingdom
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Nottingham
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United Kingdom
State/province [100] 0 0
Sheffield

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Novartis
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This extension study of was designed to evaluate the long-term safety, tolerability, and
efficacy of fingolimod (FTY720) in patients with multiple sclerosis. The Extension study was
an extension to the 24-month Core study (CFTY720D2301/NCT00289978).
Trial website
https://clinicaltrials.gov/show/NCT00662649
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications